The complete detection and genome sequencing of resistance plasmids is required to understand the co-occurrence of resistance genes on plasmids and their transmission, which is necessary to mitigate the spread of drug resistant bacterial infections. One group of multi-drug resistance plasmids of interest are the New Delhi Metallo--lactamase (NDM) associated plasmids. Bacteria pathogens with NDM genes are resistant to a broad range of beta-lactam antibiotics, including carbapenems, a mainstay for treating bacterial infections. We sequenced clinical isolates collected from patients that failed to respond to antibiotic treatments in the Hamilton-Niagara community using Next Generation Sequencing (NGS) technology, which is the standard technique for sequencing bacterial genomes. I analyzed their assembled genomes via the development of a new resistance plasmid prediction bioinformatics pipeline: RGI:Mobilome. RGI:Mobilome predicted NDM bearing plasmids in 15 isolates, along with other resistance genes on plasmids. However, the NDM plasmid predictions of all 15 isolates were fragmented due to incomplete genome assemblies, caused by repetitive sequences within bacterial genomes and use of Illumina sequencing technology. However, plasmid predictions greatly improved when we leveraged the high nucleotide accuracy of Illumina reads and the structural resolving power of long reads generated with the Oxford Nanopore Technology (ONT) to produce ‘hybrid’ genome assemblies. From the 15 putative hybrid-assembly NDM plasmids, one plasmid was a complete match to a known pKP-NDM1 plasmid, seven plasmids were “variants” of known and well-characterized plasmids, and the remaining seven plasmids were “distant homologs” of known and well-characterized plasmids, suggesting previously undescribed NDM-associated plasmids in our community. This thesis project reveals the diversity of NDM plasmid types within the Hamilton-Niagara community, which is valuable to epidemiologists and public health practitioners to devise actionable plans required to mitigate the spread of multi-drug resistance NDM plasmids and for clinicians to treat infections caused by NDM positive strains. / Thesis / Master of Science (MSc) / The spread of antimicrobial resistance often arises from the exchange of resistance plasmids between bacterial species in their immediate environment. One resistance gene carried on plasmids is the New Delhi Metallo-beta-lactamase (NDM) gene, which confers resistance to almost all beta-lactam antibiotics. To control the spread of NDM plasmids, we need to detect them completely. Using genome sequencing, we analyzed clinical isolates from patients in hospitals within the Hamilton-Niagara community for NDM plasmids. From our results, we detected one complete match to a known NDM plasmid. We also detected seven NDM-associated plasmids that are close variants of known NDM plasmids, plus another seven NDM-associated plasmid that we classified as ‘novel’ since they are widely different from known NDM plasmids. This thesis reveals the diverse NDM plasmids within the clinics of the Hamilton-Niagara community, which should guide public health workers to develop policies to mitigate the spread of resistance NDM plasmids.

<p>Människan ställs dagligen inför en mängd beslut. Att fatta beslut i dynamiska eller naturliga miljöer ställer höga krav på människan. Det är ofta mycket som står på spel, problemen är dåligt strukturerade, miljön är föränderlig och besluten måste fattas under tidspress. När flera personer ska beslut tillsammans kan beslutsfattandet organiseras på olika sätt t.ex. genom en demokratisk eller en hierarkisk organisationsstruktur. Denna rapport undersöker hurivida en hierarkisk organisationsstruktur är bättre lämpad än en demokratisk, för såväl experter som noviser, vid distribuerat beslutsfattande i en dynamisk militär domän. En experimentell studie genomfördes med studenter och officerare i en mikrovärld som skapats utifrån ett kommersiellt krigsstrategispel. I grupper om fyra personer skulle försöksdeltagarna utföra två militära uppdrag. Resultatet visar att studenterna eliminerade signifikant fler fiender än officerarna. Inga andra signifikanta skillnader erhölls. Resultatet kan ha påverkats av ett antal faktorer, studenterna hade t.ex. större vana av datorer, PC-spel och strategispel än officerarna.</p>

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An estimated 70% of bacterial infections in the United States are resistant to first-line antibiotics. Of these, among the most difficult to treat are highly resistant to carbapenems, an antibiotic class used as a last resort. Septicemia, particularly when caused by a carbapenem-resistant organism, is among the most challenging clinical scenarios to treat, with an overall mortality rate of carbapenem-resistant septicemias 63.8%. Encouragingly, if effective antimicrobial treatment begins within 1-3 hours of septic shock onset, patient survival rates are around 80%. The first section of this work describes a real-time PCR-based assay that when coupled with existing bacteria-blood separation technology, can rapidly identify genes present in a multi-drug resistant bacterial sample at physiologically significant levels (<10 CFU/mL). Primers and probes were designed which identify all subtypes of the most common carbapenemase genes in carbapenem-resistant infections in the United States: Klebsiella pneumoniae Carbapenemase (KPC); New Delhi Metallo-beta-lactamase (NDM); Cefotaximase-Munich (CTX); Cephamycin AmpC beta-lactamase (CMY); and Oxacillinase-48 (OXA-48). The information provided by this assay will supply physicians with critical drug resistance information within two hours of septicemia onset and allow for timely prescription of effective antimicrobials which correspond to the resistance gene(s) present in the causative organism. Increased understanding of the mechanisms and evolution of carbapenem resistance; in particular, the phenomenon of heteroresistance, is of significant clinical import. As such, the second section of this work examines a clinical, carbapenem-resistant E. coli isolate that when cultured in the prolonged absence of antibiotic pressure, achieves clinically relevant levels of susceptibility to imipenem and doripenem through loss of its blaNDM-1-harboring transposon at the DNA level. Through full genomic sequencing of the highly resistant population, we theorize that the resistance level was achieved through loss of genomic regions whose maintenance either exerted fitness costs in the presence of doripenem, or which encoded genes whose expression inhibited doripenem resistance via pathways that influence outer membrane porin expression. Along with the disappearance and resurgence of carbapenem resistance, emergence of a highly carbapenem-heteroresistant population occurred early and remained throughout the duration of the study.

Visualising uncertainty information has been a research area for the past decade or so, and this thesis contains the results of an experiment that examines whether prior research on icon degradation for showing uncertainty can be used in a simulated aircraft cockpit environment. Using icon degradation has been suggested as being effective to combat overconfidence bias, as well as to accurately convey information about uncertainty. Two icon sets using icon degradation were taken from prior research, and one new icon set using shape change and colour change was created for comparison. Subjects flew a flight simulator while reading icons to evaluate the uncertainty displayed, and also evaluating their own confidence in their reading. The results show that shape change leads to much higher accuracy in reading icons, and slightly higher levels of confidence. Furthermore, icon degradation results in a higher variance in reading icons and an increase in errors when no time-pressure or distraction is present. This suggests that the suitability of icon degradation for showing uncertainty is questionable in all situations, and that other design approaches such as shape change should be considered. Furthermore, problems were uncovered in the prior research that the old icons were taken from, and these problems call into question the general approach used in that research. Keywords: Uncertainty visualisation, Naturalistic decision-making, NDM, Aviation, Aircraft cockpit, Decision support, Situation assessment, Threat assessment.

The dissemination of members of the Enterobacteriaceae family with extended spectrum beta-lactamases (ESBLs) and metallo-beta-lactamases (MBLs) has become a global concern. ESBLs and MBLs have been reported in humans, domestic animals, wildlife and the environment, and their isolation frequencies are increasing rapidly worldwide.  Most studies have been performed in developed countries and quite few in developing countries, where the antibiotic consumption is often poorly controlled. To explore the environmental contamination of antibiotic resistance in Bangladesh, and of ESBLs and MBLs in particular, fecal samples from poultry and wild birds were studied in this thesis. Samples were collected from both sick birds (poultry having Escherichia coli infections) and healthy birds (free-range poultry, seagulls and crows) residing in different environmental niches. Samples from patients and fresh/sea water were included, to follow the chain of antibiotic resistance in bacteria from humans to the environment. Information regarding the antibiotic usage in poultry production was also collected. The susceptibility of avian E. coli isolates cultured with and without selective pressure was tested against antibiotics commonly used in human and veterinary medicine in Bangladesh. Special attention was paid to ESBL-producing isolates, which were further characterized genetically. The results of the studies showed that E. coli isolates from commercial poultry, free-range poultry, gulls and crows were resistant to several classes of antibiotics, and that the level and spectrum of antibiotic resistance varied between different bird populations. There was no NDM-producer found among the birds, but ESBL-producing Enterobacteriaceae could be found in up to 59% of the crows, the birds with the highest carriage rate of multiresistant  Enterobacteriaceae of all bird species studied. The most common ESBL-type was CTX-M-15, which also is the most common in the human population in Bangladesh. Birds also shared clinically important sequence types with humans, including E. coli clone O25b-ST131. In conclusion, ESBL-producing bacteria with multiresistance are easily spread to wild birds. Their opportunistic feeding behavior at poorly managed hospital waste dumps and nearby water bodies makes them into both reservoirs and active spreaders. The high level of antibiotic resistant and ESBL-producing bacteria in the bird population of Bangladesh is worrying, and there is no easy solution in sight. Nationwide programs are necessary to both improve the management of hospital waste and sewage and the control of the antibiotic usage to prevent further environmental contamination. / <p>Time of defence has been changed to 09:00 am on 2013-05-27</p>

Människan ställs dagligen inför en mängd beslut. Att fatta beslut i dynamiska eller naturliga miljöer ställer höga krav på människan. Det är ofta mycket som står på spel, problemen är dåligt strukturerade, miljön är föränderlig och besluten måste fattas under tidspress. När flera personer ska beslut tillsammans kan beslutsfattandet organiseras på olika sätt t.ex. genom en demokratisk eller en hierarkisk organisationsstruktur. Denna rapport undersöker hurivida en hierarkisk organisationsstruktur är bättre lämpad än en demokratisk, för såväl experter som noviser, vid distribuerat beslutsfattande i en dynamisk militär domän. En experimentell studie genomfördes med studenter och officerare i en mikrovärld som skapats utifrån ett kommersiellt krigsstrategispel. I grupper om fyra personer skulle försöksdeltagarna utföra två militära uppdrag. Resultatet visar att studenterna eliminerade signifikant fler fiender än officerarna. Inga andra signifikanta skillnader erhölls. Resultatet kan ha påverkats av ett antal faktorer, studenterna hade t.ex. större vana av datorer, PC-spel och strategispel än officerarna.

Flygning vid Flygvapnets flygdivisioner auktoriseras genom divisionschefernas beslut om flygning, där divisionschefen tar ansvar för både flygsäkerheten och uppgiftens lösande. Divisionschefer inom Helikopterflottiljen tar återkommande sådana beslut i utmanande situationer, där deras erfarenhet är en förutsättning för sådant naturalistiskt beslutsfattande (Naturalistic Decision Making, NDM). Samtidigt går utvecklingen mot att helikopterdivisionschefer har allt mindre flygerfarenhet, vilket riskerar att leda till felaktiga beslut med allvarliga konsekvenser. Med utgångspunkt i tidigare forskning och teori om NDM syftar undersökningen till att skapa förståelse för hur divisionschefer inom Helikopterflottiljen fattar beslut om flygning i sådana utmanande situationer. Genom att skapa en sådan förståelse samt kartlägga divisionschefernas nyttjande av tidigare erfarenheter, utbildning och tillgängliga beslutsstöd syftar uppsatsen i förlängningen också till att bidra till utvecklingen av deras utbildning, träning och beslutsstöd. Undersökningens resultat visar att divisionschefer inom Helikopterflottiljen tillämpar olika former av igenkänningsgrundade beslut (Recognition-Primed Decisions, RPD)i de undersökta situationerna, men där beslutsfattandet sker mer i team än individuellt som i RPD-teorin.Andra erfarna individer har stor betydelse för beslutsfattandet, särskilt för divisionschefer med mindre erfarenhet. Det tillgängliga beslutstödsverktyget för riskhantering nyttjas inte som föreskrivet, och kan utvecklas för att bättre passa det faktiska beslutsfattandet.

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