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Ruling ‘Others’: Cicero on Provincial Administration
Provincial administration played an important role in Roman expansion and imperialist propaganda, allowing Rome to effectively consolidate its empire. Given its significant role, many classical Latin authors have alluded to provincial administration illustrating its manifold socio-political nuances. Among these, the works of Cicero are noteworthy not only due to the various dynamics of the topic that they explore but also due to Cicero’s own political stance. In such a context, the present research focuses its attention on provincial administration during the Late Republic (133 B.C. – 43 B.C.), as reflected in selected works of Cicero. Thus, the study observes Cicero’s thoughts on how the provinces should be managed ideally. At the same time, attention is also given to Cicero’s depiction of various races (such as the Greeks, Sardinians, and Gauls) and sentiments of ethnic bias or racism expressed by Cicero towards them. Finally, the study delves into several practical complexities in provincial administration and the way they manifest racial prejudices. Such examination is deemed helpful not only to reaffirm the existence of racism in the Roman society (principally among the Roman elite) but also to better understand its place in shaping Roman imperialism as well as the ‘Roman way of thinking.
Evaluation of the Mobility Action Programme (MAP): An early intervention programme for people with musculoskeletal conditions
Embargo: 30/09/2021As the leading cause of disability in New Zealand, musculoskeletal (MSK) conditions generate health, social, and economic strains on individual quality of life and health system costs. Research indicates that one in every four adults is affected by MSK conditions, which include arthritis, osteoporosis, lower back pain, spinal disorders and injuries to the spine and limbs.1 MSK conditions are not fatal but come at a significant cost to the physical and holistic wellbeing and quality of life of those affected.
New Zealanders affected by MSK conditions can access a range of health services in primary and secondary healthcare settings. However, the management of chronic MSK conditions is largely episodic, uncoordinated, and often lacks a strong evidence base.2 The management and treatment of MSK conditions is costly; in 2009 it was estimated to comprise at least 25 percent of New Zealand’s total annual health costs.3
As a key health priority for the Ministry of Health (the Ministry), Budget 2015 confirmed a total of 44 million was targeted to support extra orthopaedic and general surgeries, and 6 million investment. The MAP was designed to align with best practice approaches to early intervention programmes for MSK conditions and the five themes of the New Zealand Health Strategy.4,5 The MAP aimed to deliver evidence informed, community-based, multidisciplinary interventions for adults with MSK conditions. It intended to support people to access advice, assessment and treatment earlier than had previously been available. The MAP’s priority groups were Māori, Pasifika and individuals living in the highest deprivation quintile. The programme ran from May 2016 to December 2019. During this time, 4,783 individuals participated in the programme.
The key objectives of the MAP were to improve the holistic well-being of adults who experience MSK conditions, reduce demand on secondary healthcare services, and address health inequity. It also aimed to provide evidence on the effectiveness of early intervention programmes targeting MSK conditions in the New Zealand context.
The Ministry established a total of 17 MAP pilot sites (MAPs). The first group of MAPs, involving seven providers, was initiated in May 2016 (Tranche 1 service providers). The second group, involving ten providers, was established in November 2016 (Tranche 2 service providers). All MAPs were designed to provide early intervention models of care, except for one MAP pilot site that targeted individuals in the later stages of their condition.6
The Ministry selected a range of providers to deliver the pilot MAPs. These included Non-Government Organisations (NGOs), private providers (such as physiotherapists, occupational therapists, and psychologists), Māori and Pasifika health providers, District Health Boards (DHBs) and Primary Health Organisation (PHOs). Providers were selected based on a range of criteria (e.g., ability to address inequity, and/or meet the unique socio-cultural and health needs of those with MSK conditions within their service areas).
The Ministry commissioned Allen + Clarke to evaluate the effectiveness and impact of the MAP, and to provide an evidence base that identifies the models and approaches that best achieve the programme’s intended outcomes. The evaluation consists of two cycles.7 This report describes findings from both cycles, with data collected from April 2018 to December 2019.
Evaluation results will be used to inform future investment in MAP-type programmes by the Ministry, DHBs, PHOs and/or other potential funders such as the Ministry of Social Development (MSD), the Accident Compensation Corporation (ACC) and private organisations. The findings will also help inform decisions about which MAPs, and which components of the MAPs will be continued, changed or stopped
The Visual Literacy of Māori Law
In recent decades, the consideration of Māori law in Aotearoa New Zealand state law has taken on a new momentum. Law schools are improving their teaching of tikanga and Māori law in compulsory and specialist law papers. The judiciary more often cites Māori law as relevant to legal decisions. The Māori Land Court has normalised the use of tikanga and Māori law in its deliberations, and the District Court has new expectations for the use of tikanga Māori in its processes. This is not to say that the way Māori law is incorporated in or recognised by these institutions of the state, and state law itself, is a settled matter, however. A conversation on this is taking place in Aotearoa New Zealand, and this thesis is intended to contribute to that conversation.
This thesis explores the questions of what Māori law is and what some of the objects of Māori law are. It reviews what the non-written visual means of documenting Māori law might be and how these means help to communicate Māori law. This thesis draws on legal theory and education and art theories of visual literacy and encoded objects to investigate whether Māori law is documented in whakairo Māori – specifically in the Māori art forms of tā moko, pou whenua, and raranga. Tā moko is the art of tattooing marks into the body, particularly the face but also the legs, body and arms. Pou whenua are tall upright wooden carvings placed in or on the ground and used to identify whakapapa to and mana whenua over lands and waters. Raranga is the art of weaving, which is extensively used in the making of garments and domestic tools.
Māori law is documented in objects and visual markings just as objects (such as law books) and visual markings (such as writing) document state law in Aotearoa New Zealand. This thesis considers the evidence for that documentation of Māori law. Seven core principles of Māori law are explored and applied to three chosen forms of whakairo Māori.
This thesis acknowledges how Indigenous jurists have critiqued Western attitudes about Indigenous laws, confirming the resilience of both Māori law in Aotearoa New Zealand and contemporary Indigenous jurisprudence. The thesis demonstrates that Indigenous peoples, including Māori, can be said to have documented their law in creative art forms. There are examples of whakairo Māori that can be read as encoded with the principles of Māori law. As such, this thesis establishes that Māori were a literate culture pre-colonisation. It suggests that any failure to understand whakairo Māori as documenting legal information is a failure of literacy by the reader – not a failure of literacy of te ao Māori itself
Profile decomposition for the Klein-Gordon equation
We use refined Strichartz estimates to prove profile decompositions for the wave equation in ̇H1/2(Rd) and for the Klein-Gordon equation in H1/2(Rd); the former is an alternative proof of a result originally obtained by Ramos, while the latter is a new result
Probiotics and Acute Otitis Media (AOM)
Introduction:
Acute otitis media (AOM) is the most common bacterial infection in children for which parents seek medical advice (1). Acute otitis media commonly presents with fever, ear pain, and hearing impairment. Common otopathogens include Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (2,3). Colonisation with these organisms at a young age is associated with an increased risk of developing AOM in young children (1). Despite vaccination against strains of S. pneumoniae and NTHi, there has been little impact on the overall prevalence of otitis media. The lack of vaccine impact is primarily due to an increase in disease attributable to non-vaccinated strains (2,4). Management of non-resolving AOM involves the use of broad-spectrum antibiotics. However, frequent and inappropriate use of antibiotics is associated with increasing antimicrobial resistance and facilitates colonisation with resistant strains of pathogenic species (5,6). Thus, in light of the high prevalence and the considerable burden of AOM in the community, new strategies for preventing recurrent AOM are needed.
Aims:
1. To review the literature on the use of probiotics in the prevention of AOM.
2. To determine the efficacy of probiotics against otopathogens.
3. To assess the ability of probiotics to colonise the nasopharynx.
Methods:
A literature review was carried out across databases, Medline, EMBASE, PubMed and Cochrane, using keywords related to probiotics, otitis media and ear infection. The search phrases were searched as medical subject headings (MeSH), and as a subject, terms with possible endings were denoted with “*” to expand the search. The literature title and the abstract were then screened and related articles were obtained and critically analysed. Meta-analysis was then conducted on homogenous data to determine the overall benefit of probiotics on AOM.
To determine the efficacy of Streptococcus salivarius K 12 on the inhibition of otopathogens. Isolates of otopathogens from otitis-media prone children were cultured and plated against S. salivarius K12.
To determine the ability to colonise the nasopharynx, fifty healthy adult volunteers were recruited and randomised to S. salivarius given orally and nasally. Pre-colonisation swabs were taken followed by a course of oral antibiotics. A two-week course of probiotics was provided to the volunteers. One week after the completion of probiotics, the individuals were swabbed again. Both swabs were analysed with real-time quantitative polymerase chain reaction. (RT-qPCR).
Results:
From the literature review, thirteen studies were identified. Overall, the study designs were heterogeneous and were of moderate quality. Five of the studies had enough similarity in population selection, methodology and outcome measure for meta-analysis. The conglomerate data from these five studies showed no demonstrable prophylactic effect for the use of probiotics on AOM. Probiotics species varied widely in the literature and also in the route of administration. The evidence for the use of probiotics in AOM was therefore conflicting and insufficient to support their clinical use in the prevention of AOM.
In the trial of probiotics versus otopathogens isolates, 107 known otopathogens isolates from a previous study lead by Mills et al. were culturable and identifiable. When tested against the bacteriocin-like inhibitory substance (BLIS) from S. salivarius K12, 48% had demonstrable inhibition. Overall, complete inhibition of all S. pneumoniae was witnessed with partial to no inhibition of other known otopathogens.
The colonisation trial did not yield sufficient data to suggest or refute the ability of the S. salivarius to colonise the nasopharynx or alter its microflora. However, it has been demonstrated that the tolerability of the nasal route of probiotics administration was not as good as previously thought.
Significance:
The available literature on the use of probiotics for AOM is of low quality and quantity. Although S. salivarius is a potential probiotic choice for AOM prophylaxis, it only demonstrates inhibition in less than half of the otopathogen isolates. Therefore, it is unlikely to be effective, if used alone. The colonisation trial was unable to be completed as proposed due to unanticipated complications, but it did hint that the tolerability and safety of S. salivarius K12 need to be studied further
Real-time in situ testing of antibiotic resistance
Antimicrobial resistance (AMR) is one of the top ten threats to public health according to the World Health Organization (WHO), with approximately 700, 000 deaths recorded per year due to infections with drug-resistant bacteria. Furthermore, antibacterial treatments are often initiated with the wrong antibacterials without proper identification of the causative agent and/or empirical antimicrobial therapies are prescribed that can result in increased mortality and healthcare costs. Conventional methods used to diagnose infection and determine antimicrobial susceptibility often have long turnaround times, are expensive and labour intensive. There is a need for methods and technologies to enable rapid antimicrobial susceptibility testing (AST) with potential for point-of-care testing (POCT) to combat AMR.
The hypothesis for this research was that a reporter/detector-based assay could be developed that would enable real-time, in situ, testing of antibacterial resistance. The reporter would be modified/activated by an enzyme that was upregulated in bacteria cells in response to the stress induced by exposure to an antimicrobial agent. The proposed AST would involve injecting a test dose of an antimicrobial agent into the patient along with the inactive reporter, co-encapsulated into a particulate delivery system. A highly sensitive assay would then be utilised to detect the modified/activated reporter in a drop of blood at the patient’s bedside.
Four different enzymes known to be upregulated in stressed human pathogens (Escherichia coli and Staphylococcus aureus) were investigated; caseinolytic protease proteolytic (ClpP) subunit, the endoribonuclease toxin (MazF), recombination protein A (RecA) and sortase A (SrtA). The expression of the genes encoding these enzymes was investigated in antimicrobial susceptible and resistant clinical isolates of E. coli and S. aureus grown in vitro, after treatment with antibacterials, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Following treatment susceptible, but not resistant, S. aureus were found to upregulate all four genes. This upregulation was not detected in E. coli, likely due to assay-related issues. These findings were further investigated in both antibacterial-treated and untreated bacteria by a proteomics approach to assess protein levels. Proteomics results supported the upregulation of RecA in both E. coli and S. aureus; and ClpP and SrtA in antibacterial-treated S. aureus. A RecA protein assay was able to confirm the functional activity of RecA in antibacterial-treated susceptible, but not resistant, E. coli.
In order to achieve co-delivery of antibacterial and reporter, a liposomal delivery system was developed. Optimisation of both cationic and neutral non-PEGylated and PEGylated liposomes was performed to produce liposomes with the required size, polydispersity, drug loading and zeta potential. Optimised cationic non-PEGylated liposomal-cefotaxime showed comparable in vitro antibacterial activity compared to free cefotaxime (a broad-spectrum antibiotic) when tested against E. coli. To further investigate the mechanism of uptake of liposomal-antibacterial in bacteria, a novel assay for the determination of subcellular drug delivery in E. coli lacking the TolC outer membrane efflux pump (tolC) was utilised. The bacteria were further modified such that streptavidin which has high affinity for biotin was localised into the periplasm or cytoplasm thereby allowing compartment-specific localisation of drug to be examined. Bacteria were incubated with a cyclooctyne-biotin probe which would attach to the localised streptavidin before being incubated with azido-containing compounds (luciferin or cefoxitin) delivered as free drug or encapsulated into liposomes. Any azido-containing compound taken up would undergo a click reaction with the cyclooctyne-biotin, with any unreacted cyclooctyne -biotin probe then being measured. Improved uptake of both azido compounds into the periplasm of tolC E. coli and decreased cytoplasmic localisation was observed for cationic liposomal formulations as compared to neutral formulations or free drug. This study provided the potential formulation to be used to deliver both antibacterial and reporter.
The next steps in development of the in situ AST were the design and development of reporters for ClpP and RecA. High performance liquid chromatography (HPLC)-based techniques were developed and optimised to measure activation of the proposed reporters after exposure to the recombinant enzymes. A ClpP reporter consisting of a modified synthetic peptide was cleaved at Met-Ala bonds in the presence of acyldepsipeptide (ADEP)1 and ClpP. For RecA, a modified and truncated version of LexA protein was synthesised and purified to use as the reporter. Recombinant RecA was able to cleave the reporter in the presence of ssDNA and ATP-γ-S at Ala-Gly bonds. The detection of RecA-mediated cleavage of the LexA reporter was then further developed using aptamer-based technologies and mass spectroscopy. Analysis of antibacterial-treated and untreated E. coli samples by MS could detect the presence of the cleaved LexA reporter product, however the product was present in all samples. The background level of cleavage could be attributed to RecA expression in cultures due to the stress of in vitro culture.
The aim of this study was to investigate if a real-time in situ AST could be developed. The thesis provides important data on the feasibility of this approach. A number of potential bacterial targets upregulated by antibacterial-treated susceptible bacteria were identified along with potential reporters. A formulation suitable for the co-delivery of antibacterial and the reporter was identified and the mechanism of uptake of the formulation was investigated. The need for a sensitive and quantitative assay for detection of the reporter was confirmed. Based on the work in this thesis, the findings confirmed the potential of this approach for the development of a rapid, point-of-care testing for AST in future, using the LexA reporter to detect in vitro and in vivo resistance of bacteria to killing with antimicrobial agents
From rags to rituals : an ethnography of menstruation among New Zealand pakeha women
This thesis examines menstruation among New Zealand Pakeha women from. an anthropological perspective. It takes its theoretical direction from feminist discourse that seeks to give visibility to women's issues and acknowledges the importance of recognising the differences between women. The thesis attempts to be a vehicle through which women's experiences can be heard, so to expose details about menstruation that have been overlooked, ignored or not conceived. In doing so, it
challenges universal assumptions that overshadow considerations of difference. Discussion builds from the personal reality of being a menstruator, to managing menstruation in the public environment, to the meaning women give to their own experience. The thesis also provides rare insight into the sensitive issues of sexual violation converging with menstruation. Findings suggest that the experience of each woman who menstruates is shaped by more than physiological
processes and cultural influences. The research employed ethnographic methods requiring two and a half years of field work in a South Island community of 6000 people. This time involved collecting observations and conducting in-depth interviews with seventy-five women between the ages of ten and eighty-one
The short- and long-term effects of television pace and fantasy rates on children's executive functioning
Television’s introduction in the 1950s spurred long-lived concerns for the consequences of television viewing on children’s cognitive development that still persist today. Historically, critiques have focused on child-directed shows’ fast pacing (e.g., high number of camera cuts or scene changes), yet recent experimental research suggests that the fantasy (e.g., number of unrealistic or impossible characters and events) of the shows may be more detrimental than fast pacing. It is theorised that high pace and fantasy rates may overtax children’s cognitive abilities while viewing leading to lowered executive function abilities immediately and longitudinally. The overarching aim of this thesis was to explore whether the pace and fantasy rates of child-directed shows have negative effects on child viewers’ executive functioning. Study 1 involved a parental questionnaire to gather up-to-date data on children’s access to and technology use in Aotearoa New Zealand. The short-term effects of pace and fantasy were investigated through a partial replication experiment of the negative effect of fast-paced and fantastical content (Study 2A) and two meta-analyses of the existing experimental research (Study 2B). The long-term effects were explored in Study 3 by coding the pace and fantasy rates of the shows habitually watched by a longitudinal cohort of Aotearoa New Zealand children, and using regression analysis to see whether viewing in early childhood predicted executive functioning in later childhood. Together, these studies suggest that there are weak, non-significant relationships between pace or fantasy rates and executive functioning in both the short- and long-term
Te Pūrongo ā-Tau Tekau mā Whā o te Komiti Arotake Mate Pēpi, Mate Whaea Hoki
This monitoring report outlines some of the trends in mortality in babies and mothers, and serious morbidity from neonatal encephalopathy. Deaths are usually multifactorial in nature – usually a death has more than one cause. The aim of this work is to monitor trends and look at systems issues that could be modified to prevent future deaths
Genetic insights into neurogenesis through the study of periventricular nodular heterotopia
The carefully orchestrated process of neurogenesis governs the expansion of the developing cortex, with the extension of these neurogenic pathways underpinning the increasingly complex cortex in the primate-lineage. This expansion has co-occurred with the rapid evolution of genomic loci speculated to be responsible for the regulation of these pathways. Disruption of these tightly regulated processes results in abnormal structural changes in the developed cortex, known as cortical malformations.
Periventricular nodular heterotopia (PVNH) is a genetically and phenotypically heterogeneous cortical malformation characterised by the mispositioning of grey matter along the surface of the lateral ventricles and is associated with epilepsy and developmental delay. Currently, only a third of patients have a molecular diagnosis, presenting a considerable diagnostic gap. Further identification of genetic determinants of this phenotype will highlight cellular pathways critical for neurogenesis, while simultaneously improving patient management. This thesis details the utilisation of high- throughput sequencing analyses on a cohort of 202 PVNH families in combination with functional assays to improve current diagnostic rates.
The first aspect of this study relates to the assessment of data quality in the current cohort, spurred by the discovery of multiple seemingly pathogenic changes resulting from vector contamination. Consequently, a rigorous workflow of quality control steps was employed to assess the extent of vector contamination and similar quality issues in the PVNH cohort. This process revealed weaknesses in the currently available quality control tools, requiring the development of a new programme, that led to the detection of 11 vector contaminations events, allowing for appropriate mitigation.
The primary variant analyses of this study focused on a subcohort of 137 PVNH patients and their unaffected parents. These trio analyses sought to assess the contribution of coding de novo variation and biallelic genotypes to the pathogenesis of PVNH. Pathogenic variants were discovered for 17 patients, with variant recurrence observed in two genes: FLNA (n = 4), a known PVNH gene and, a novel gene SON (n = 5), associated with ZTTK (Zhu-Tokita-Takenouchi-Kim) syndrome, a severe multi-system congenital malformation disorder. The remaining pathogenic variants were associated with a broad range of neurodevelopmental phenotypes. This finding suggests that a significant proportion of PVNH cases occur in association with known neurodevelopmental diseases, where PVNH is a rare or currently under appreciated phenotypic component.
The third aspect of this project involved further utilisation of exploratory variant analyses in the 102 unresolved whole-genome sequence PVNH trios. This included profiling several forms of variation known to be associated with other neurodevelopmental diseases, including mosaic variation, structural changes, and non- coding variants. In addition, 56 PVNH patients without complete parental information were screened for pathogenic variation using a restricted gene filtering approach, under the hypothesis that a considerable portion of PVNH cases are associated with a broad range of neurodevelopmental disorders without currently recognised associations with PVNH. In combination, these analyses led to the discovery of a further 14 pathogenic variants, including another pathogenic variant in SON.
Finally, the association of SON with PVNH was further explored. This was achieved using a combination of transcriptomic analyses focused on understanding differential transcript splicing and expression, and functional analyses aimed at understanding the differential localisation and protein interactors of SON isoforms. These analyses led to the identification of a currently unannotated protein-coding transcript of SON, that may represent a critical element in the pathogenesis of ZTTK syndrome. Proteomic analyses that were aimed at assessing the binding partners of each RNA-binding isoform of SON, further supported this idea. In addition, this proteomic information was used to prioritise candidate variants identified in the unresolved PVNH trio subcohort, under the hypothesis that shared pathways are being differentially disrupted in this condition.
Together, these analyses represent a comprehensive genomic examination of a cohort of PVNH families and contribute insights into the complex genetic architecture underlying this condition, while providing diagnostic answers for 31 families. Further, this study provides a range of analytical frameworks for the identification of quality anomalies and candidate variation, which are broadly applicable to the study of the genomic determinants of rare diseases using high-throughput sequencing data