title: Whole genome sequencing of Mycobacterium tuberculosis reveals slow growth and low mutation rates during latent infections in humans

authors: Colangeli, Roberto

subjects: genome sequencing

abstract: Very little is known about the growth and mutation rates of Mycobacterium tuberculosis during latent infection in humans. However, studies in rhesus macaques have suggested that latent infections have mutation rates that are higher than that observed during active tuberculosis disease. Elevated mutation rates are presumed risk factors for the development of drug resistance. Therefore, the investigation of mutation rates during human latency is of high importance. We performed whole genome mutation analysis of M. tuberculosis isolates from a multi-decade tuberculosis outbreak of the New Zealand Rangipo strain. We used epidemiological and phylogenetic analysis to identify four cases of tuberculosis acquired from the same index case. Two of the tuberculosis cases occurred within two years of exposure and were classified as recently transmitted tuberculosis. Two other cases occurred more than 20 years after exposure and were classified as reactivation of latent M. tuberculosis infections. Mutation rates were compared between the two recently transmitted pairs versus the two latent pairs. Mean mutation rates assuming 20 hour generation times were 5.5X10⁻¹⁰ mutations/bp/generation for recently transmitted tuberculosis and 7.3X10⁻¹¹ mutations/bp/generation for latent tuberculosis. Generation time versus mutation rate curves were also significantly higher for recently transmitted tuberculosis across all replication rates (p = 0.006). Assuming identical replication and mutation rates among all isolates in the final two years before disease reactivation, the u20hr mutation rate attributable to the remaining latent period was 1.6×10⁻¹¹ mutations/bp/generation, or approximately 30 fold less than that calculated during the two years immediately before disease. Mutations attributable to oxidative stress as might be caused by bacterial exposure to the host immune system were not increased in latent infections. In conclusion, we did not find any evidence to suggest elevated mutation rates during tuberculosis latency in humans, unlike the situation in rhesus macaques.

text: Whole genome sequencing of Mycobacterium tuberculosis reveals slow growth and low mutation rates during latent infections in humans Very little is known about the growth and mutation rates of Mycobacterium tuberculosis during latent infection in humans. However, studies in rhesus macaques have suggested that latent infections have mutation rates that are higher than that observed during active tuberculosis disease. Elevated mutation rates are presumed risk factors for the development of drug resistance. Therefore, the investigation of mutation rates during human latency is of high importance. We performed whole genome mutation analysis of M. tuberculosis isolates from a multi-decade tuberculosis outbreak of the New Zealand Rangipo strain. We used epidemiological and phylogenetic analysis to identify four cases of tuberculosis acquired from the same index case. Two of the tuberculosis cases occurred within two years of exposure and were classified as recently transmitted tuberculosis. Two other cases occurred more than 20 years after exposure and were classified as reactivation of latent M. tuberculosis infections. Mutation rates were compared between the two recently transmitted pairs versus the two latent pairs. Mean mutation rates assuming 20 hour generation times were 5.5X10⁻¹⁰ mutations/bp/generation for recently transmitted tuberculosis and 7.3X10⁻¹¹ mutations/bp/generation for latent tuberculosis. Generation time versus mutation rate curves were also significantly higher for recently transmitted tuberculosis across all replication rates (p = 0.006). Assuming identical replication and mutation rates among all isolates in the final two years before disease reactivation, the u20hr mutation rate attributable to the remaining latent period was 1.6×10⁻¹¹ mutations/bp/generation, or approximately 30 fold less than that calculated during the two years immediately before disease. Mutations attributable to oxidative stress as might be caused by bacterial exposure to the host immune system were not increased in latent infections. In conclusion, we did not find any evidence to suggest elevated mutation rates during tuberculosis latency in humans, unlike the situation in rhesus macaques.

year: 2014

title: Future trends in I&M: The next generation of measurement technology for medicinal cannabis production

authors: Ooi, Melanie Po-Leen

abstract: Across the globe, legislation surrounding the application of cannabinoid compounds towards human health is gaining momentum. Corresponding with new regulations is a dramatic increase in cannabinoid-based treatment options—from just a few drugs in the early 2000s to now over 300 medical products currently in human trials for ailments such as post-traumatic stress disorder, nervous system degeneration, depression, epileptic seizures, Parkinson's disease, multiple sclerosis and schizophrenia. Consumption of medicinal cannabis is currently legal in over 40 countries and 33 states in the US, with the global sector estimated by some industry analysts to be worth over USD 62.6 billion by 2024 [1]. Legalization of medicinal cannabis is under consideration in over a dozen other countries, and more jurisdictions can be expected to follow suit if the evidence for efficacy of medicinal cannabis increases.

text: Future trends in I&M: The next generation of measurement technology for medicinal cannabis production Across the globe, legislation surrounding the application of cannabinoid compounds towards human health is gaining momentum. Corresponding with new regulations is a dramatic increase in cannabinoid-based treatment options—from just a few drugs in the early 2000s to now over 300 medical products currently in human trials for ailments such as post-traumatic stress disorder, nervous system degeneration, depression, epileptic seizures, Parkinson's disease, multiple sclerosis and schizophrenia. Consumption of medicinal cannabis is currently legal in over 40 countries and 33 states in the US, with the global sector estimated by some industry analysts to be worth over USD 62.6 billion by 2024 [1]. Legalization of medicinal cannabis is under consideration in over a dozen other countries, and more jurisdictions can be expected to follow suit if the evidence for efficacy of medicinal cannabis increases.

year: 2020

title: Kaitiakitanga o te Taiao - Reconciling Legislative Provisions and Outcomes for Māori

authors: Kennedy, Nathan Charles Karaua

subjects: Kaitiakitanga

abstract: The Resource Management Act (1991) (RMA) was heralded as internationally ground-breaking for its integrated approach, and for cementing 'sustainable management' as its overarching purpose. It was ground-breaking also for its recognition of First Nations’ rights and values. This includes directing decision-makers to recognise and provide for the relationship of Māori and their culture and traditions with their ancestral lands, waters and treasured resources, to have particular regard to Māori customary practices, and to take into account the principles of the Treaty of Waitangi. The RMA provides for councils to transfer or delegate functions and powers to Māori, and for joint management arrangements.
In 16 years as environment officer for my iwi, I witnessed the failure of the RMA to protect Māori values and interests. This experience prompted me to undertake research to thoroughly investigate outcomes of the operation of the RMA for Māori. Two questions framed my research; the first asking whether kaitiaki have been empowered by the Māori provisions in the RMA, and the second seeking to determine overall outcomes for Māori from the Act.
Assessing such outcomes required an understanding of Māori values and interests, evaluation of the law, of the statutory plans that govern council administration of the RMA, implementation of these by councils and the Crown, and their treatment by the courts. To answer the two questions I present in this thesis a geographically focused study of two take (causes or significant issues) at Whangamatā, the construction of a marina, and the removal of mangroves.
I compare Ngāti Whanaunga experiences with those of Māori nationally. By doing so I provide the evidence base for an 'overall broad judgement' (as the RMA requires) that despite apparent empowerment by the Act and its statutory plans, Māori have suffered widespread and significantly negative outcomes under the RMA. Rather than being empowered, Māori struggle to participate in planning processes, and see ancestral values and interests eroded by waves of resource consent processes, in which effects on Māori are little considered.

text: Kaitiakitanga o te Taiao - Reconciling Legislative Provisions and Outcomes for Māori The Resource Management Act (1991) (RMA) was heralded as internationally ground-breaking for its integrated approach, and for cementing 'sustainable management' as its overarching purpose. It was ground-breaking also for its recognition of First Nations’ rights and values. This includes directing decision-makers to recognise and provide for the relationship of Māori and their culture and traditions with their ancestral lands, waters and treasured resources, to have particular regard to Māori customary practices, and to take into account the principles of the Treaty of Waitangi. The RMA provides for councils to transfer or delegate functions and powers to Māori, and for joint management arrangements.
In 16 years as environment officer for my iwi, I witnessed the failure of the RMA to protect Māori values and interests. This experience prompted me to undertake research to thoroughly investigate outcomes of the operation of the RMA for Māori. Two questions framed my research; the first asking whether kaitiaki have been empowered by the Māori provisions in the RMA, and the second seeking to determine overall outcomes for Māori from the Act.
Assessing such outcomes required an understanding of Māori values and interests, evaluation of the law, of the statutory plans that govern council administration of the RMA, implementation of these by councils and the Crown, and their treatment by the courts. To answer the two questions I present in this thesis a geographically focused study of two take (causes or significant issues) at Whangamatā, the construction of a marina, and the removal of mangroves.
I compare Ngāti Whanaunga experiences with those of Māori nationally. By doing so I provide the evidence base for an 'overall broad judgement' (as the RMA requires) that despite apparent empowerment by the Act and its statutory plans, Māori have suffered widespread and significantly negative outcomes under the RMA. Rather than being empowered, Māori struggle to participate in planning processes, and see ancestral values and interests eroded by waves of resource consent processes, in which effects on Māori are little considered.

year: 2017