10 research outputs found
Phylo-epidemiological and pathogenic diversity of Mycobacterium tuberculosis strains in London with implications for vaccine develpoment
No full textPhDApproximately one-third of the global population is infected with tuberculosis causing
approximately 1.7 million deaths. Currently, the BCG vaccine is used to protect
against TB, but it cannot prevent primary infection or reactivation of latent infection.
Ideally a vaccine should protect against a diverse array of Mycobacterium
tuberculosis strains and promote a strong, long-lasting TH1 cell-mediated immune
response. Whilst evaluating the efficiency of novel vaccines using laboratory control
strains (M. tuberculosis H37Rv, H37Ra and M. bovis-BCG), it is important to test
efficacy against a representative panel of wild-type circulating strains. In England
42.2% of TB cases are reported in London and the diversity of nationalities generates
a diverse pool of strains consisting of globally representative TB strains. The aim of
the study was to construct a representative panel of strains for vaccine evaluation
studies and general TB research.
Common M. tuberculosis strains were identified by performing molecular MIRUVNTR
and spoligotyping on 2363 isolates from TB cases reported in London during a
one-year period. Epidemiological analysis demonstrated there were representatives
from 13 global regions, including high TB burden countries. An algorithm was
designed to select strains for a preliminary panel based on associations between
MTBC families in clusters of more common strains, the country of birth and VNTR
sub-clusters. The preliminary panel contained 42 MTBC strains belonging to 10
MTBC families from patients born in 17 countries.
Results of phylogenetic analysis of all 2363 isolates was used to select a smaller panel
of strains from the preliminary panel to represent MTBC lineages to investigate if
wild-type strains were phenotypically similar. The final panel included five strains
from each of the Baker et al., 2004 M. tuberculosis lineages (M. tuberculosis Beijing,
LAM10, two CAS, EAI5 strains representing lineage I, II, III, IV, respectively) and
an M. africanum strain.
In vitro tissue culture experiments demonstrated significantly higher growth of the
Beijing strain compared to the other wild-type and laboratory strains. Higher growth
rates of this strain were also observed in a cell-free culture system. Aerosol challenge
of guinea pigs with wild-type strains showed a quicker dissemination of the EAI5 strain from the lung to the spleen 16 days post-challenge, but significantly higher
c.f.u. count of the Beijing strain in the spleen 56 days post-challenge. Collectively, the
data demonstrated that there are phenotypic differences between wild-type circulating
MTBC strains
Emerg Infect Dis
No full textTo inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >or=5 copies at exact tandem repeat (ETR) A, >or=2 at mycobacterial interspersed repetitive unit 24, and >or=3 at ETR-B associated with the East African-Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity
Emerg Infect Dis
No full textTo address conflicting results about the stability of variable number tandem repeat (VNTR) loci and their value in prospective molecular epidemiology of Mycobacterium tuberculosis, we conducted a large prospective population-based analysis of all M. tuberculosis strains in a metropolitan setting. Optimal and reproducible conditions for reliable PCR and fragment analysis, comprising enzymes, denaturing conditions, and capillary temperature, were identified for a panel of hypervariable loci, including 3232, 2163a, 1982, and 4052. A total of 2,261 individual M. tuberculosis isolates and 265 sets of serial isolates were analyzed by using a standardized 15-loci VNTR panel, then an optimized hypervariable loci panel. The discriminative ability of loci varied substantially; locus VNTR 3232 varied the most, with 19 allelic variants and Hunter-Gaston index value of 0.909. Hypervariable loci should be included in standardized panels because they can provide consistent comparable results at multiple settings, provided the proposed conditions are adhered to
Associations between Mycobacterium tuberculosis strains and phenotypes
No full textTo inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: ≥5 copies at exact tandem repeat (ETR) A, ≥2 at mycobacterial interspersed repetitive unit 24, and ≥3 at ETR-B associated with the East African-Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity
Discriminatory ability of hypervariable variable number tandem repeat loci in population-based analysis of Mycobacterium tuberculosis strains, London, UK
No full textTo address conflicting results about the stability of variable number tandem repeat (VNTR) loci and their value in prospective molecular epidemiology of Mycobacterium tuberculosis, we conducted a large prospective population-based analysis of all M. tuberculosis strains in a metropolitan setting. Optimal and reproducible conditions for reliable PCR and fragment analysis, comprising enzymes, denaturing conditions, and capillary temperature, were identified for a panel of hypervariable loci, including 3232, 2163a, 1982, and 4052. A total of 2,261 individual M. tuberculosis isolates and 265 sets of serial isolates were analyzed by using a standardized 15-loci VNTR panel, then an optimized hypervariable loci panel. The discriminative ability of loci varied substantially; locus VNTR 3232 varied the most, with 19 allelic variants and Hunter-Gaston index value of 0.909 . Hypervariable loci should be included in standardized panels because they can provide consistent comparable results at multiple settings, provided the proposed conditions are adhered to
Nigerian Christians vs. Nigerian Muslims: Secularism, Violence, and The Rhetoric of Blame
No full textIn this thesis I will be discussing in detail the conflict between the Christians and Muslims in Nigeria. I started my research originally in London conducting\ud
interviews and talking to many Nigerian Christians and Nigerian Muslims about the\ud
conflict between these two religious groups. While there I got a great perspective on how these Nigerians felt about the conflict first hand, but I was still left with many questions.\ud
The majority of the Nigerians I interviewed were Christian, but I wanted to know which religious group was truly responsible for the violence? What were the underlying issues revolved around the conflict? What could be done to solve the conflict? While reading and researching, I came across a series Studies in Christian-Muslims\ud
Relations by a Christian author Jan H. Boer. Boer had spent over thirty\ud
years studying in Nigeria about Christians and Muslims, and considered himself an\ud
expert on colonialism. In this nine volume series, Boer answered some of these same questions I had about which religious group was to blame and what the\ud
underlying issues around the violence in Nigeria were. Boer's goal was to end the violence in Nigeria by establishing parameters for each religious group to follow so there could be peaceful coexistence, he believed the only way for his goal to be achieved was for the Christians to become more\ud
holistic, and the Muslims to have an open mind toward pluralism.\ud
In my thesis, I will be doing an in depth analysis of Boer's argument and his rhetorical structures of blame. He starts out with a claim about the negativity of\ud
secularism, which is a major point to this argument. Boer believes that secularism is the underlying issue of the conflict because it derails Christian biblical thought, and\ud
goes against the Muslim Sharia Law. Boer showcases many rhetorical structures of blame, but they are related to his belief that Muslims are the essential religious group to blame for the violence in Nigeria. Some of these rhetorical structures of blame Boer discusses include the\ud
Sharia Law, the Muslim dominant nature, and the teaching of justified Muslim violence. In the end, Boer leaves some unanswered questions on the table, especially\ud
about the positive and negative intentions of secularism, but overall, these rhetorical structures of blame exist and have been focused around the Muslims. Boer's series goes from identifying who is responsible for the conflict, to what the\ud
issues are behind the violence, and finally what can be done to stop it and bring peace for the future. I also offer my own advice about what can be done for the\ud
Christians and Muslims to live together peacefully in Nigeria
Saint Paul, the Ismāʻīlīs, and the end of the world : new visions of the religious law
No full textHasan Salah, a 13th-century exponent of the Isma'ili qiyamat doctrine, and Saint Paul the Apostle, the author of much of the New Testament, believed that during their lifetimes, a Messiah had come. The arrival of the Messiah triggered the end time; in this new time of sacredness, both authors believed that it was impossible---and even counterproductive---to gain salvation by following the traditional religious law. This thesis juxtaposes both authors' conceptions of the religious law, highlighting how each author reinterprets scripture to argue that the law simply cannot bring salvation in this new time. It then discusses how, in place of the law, both authors advocate a new, more individual soteriology structured around the Messianic figure. This thesis then discusses the seven shared structural features of both eschatologically based theologies, strengthening the corpus of evidence suggesting that Isma'ili thinkers often incorporate specifically Christian elements into their theology
Taʾwīl of an Apocalyptic Transcript I: The Book of Unveiling
No full textThis chapter examines the apocalyptic symbolism of one of the first works of taʾwīl attributed to the Fatimids, the Kitāb al-kashf, or Book of Unveiling. After a brief introduction to the apocalyptic elements of the Quran, the chapter shows how the author of the Kitāb al-kashf interpreted the text to argue that the Quran’s descriptions of the end of time in actuality referred to the coming of the awaited eschatological figure, the mahdi. The chapter argues that the Kitāb al-kashf’s taʾwīl of the Quran’s eschatological and apocalyptic imagery created a new transcript whose soteriological structure was centred around belief in and support for the mahdi and his cause.</p
Survival of Civilian and Prisoner Drug-Sensitive, Multi- and Extensive Drug- Resistant Tuberculosis Cohorts Prospectively Followed in Russia
No full textThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Assessment of a complete truck operating under dual-mode dual-fuel combustion in real life applications: Performance and emissions analysis
No full text[EN] The dual-mode dual-fuel (DMDF) strategy has been demonstrated to be a potential combustion mode to cover all the engine map with low-to-moderate NOx and soot emissions and high efficiency simultaneously. This can be accomplished by modifying the injection strategy to promote a fully premixed or a dual-fuel diffusive combustion depending on the operating conditions. The main limitation of the DMDF are the high concentrations of unburned hydrocarbons and carbon monoxide coupled with low exhaust temperatures, which can be a challenge for the stock diesel oxidation catalyst (DOC). Moreover, the use of a diffusive combustion combined with high EGR rates to avoid mechanical issues at high load enhances the soot formation, which can compromise the final soot levels in a homologation cycle. To evaluate these aspects, this work studies the performance and emissions of a DMDF truck concept along a WHVC and different in-service conformity cycles through vehicle systems simulations. For both types of cycles, five payloads were tested (0%, 25%, 50%, 75% and 100%) to evaluate the impact of this parameter on the operating points distribution inside the DMDF map. The first results show that the DMDF concept provides engine-out NOx levels below the EUVI regulation at normative payload (50%) with similar fuel consumption than the conventional diesel truck. On the other hand, the engine-out HC and CO emissions exceed their respective limits in all the cases, while the engine-out soot emissions only reach the EUVI levels up to 25% payload. By this reason, the stock DOC and diesel particulate filter from the conventional diesel truck were modelled and fitted to the DMDF truck model. The results evidenced that the use of these two ATS allows to achieve the EUVI limits in terms of tailpipe HC, CO and soot independently on the cycle and payload analyzed. Moreover, considering the tailpipe emissions values achieved with ATS at 50% payload, it can be inferred that both devices could be downsized for the DMDF application as compared to the conventional ATS for diesel applications.The authors thanks ARAMCO Overseas Company and VOLVO Group Trucks Technology for supporting this research. The authors acknowledge European Regional Development Fund (FEDER) and Spanish Ministerio de Economia y Competitividad for partially supporting this research through TRANCO project (TRA2017-87694-R). The authors also acknowledge the Universitat Polit`ecnica de Val`encia for partially supporting this research through Convocatoria de ayudas a Primeros Proyectos de Investigacion (SP20180148). The author R. 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