Journal Articles
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Item Cytotoxic aggregation and amyloid formation by the myostatin precursor protein(Public Library of Science, 2010) Starck CS; Sutherland Smith AJMyostatin, a negative regulator of muscle growth, has been implicated in sporadic inclusion body myositis (sIBM). sIBM is the most common age-related muscle-wastage disease with a pathogenesis similar to that of amyloid disorders such as Alzheimer's and Parkinson's diseases. Myostatin precursor protein (MstnPP) has been shown to associate with large molecular weight filamentous inclusions containing the Alzheimer's amyloid beta peptide in sIBM tissue, and MstnPP is upregulated following ER stress. The mechanism for how MstnPP contributes to disease pathogenesis is unknown. Here, we show for the first time that MstnPP is capable of forming amyloid fibrils in vitro. When MstnPP-containing Escherichia coli inclusion bodies are refolded and purified, a proportion of MstnPP spontaneously misfolds into amyloid-like aggregates as characterised by electron microscopy and binding of the amyloid-specific dye thioflavin T. When subjected to a slightly acidic pH and elevated temperature, the aggregates form straight and unbranched amyloid fibrils 15 nm in diameter and also exhibit higher order amyloid structures. Circular dichroism spectroscopy reveals that the amyloid fibrils are dominated by β-sheet and that their formation occurs via a conformational change that occurs at a physiologically relevant temperature. Importantly, MstnPP aggregates and protofibrils have a negative effect on the viability of myoblasts. These novel results show that the myostatin precursor protein is capable of forming amyloid structures in vitro with implications for a role in sIBM pathogenesis.Item Quantifying risk factors for human brucellosis in rural northern Tanzania(PloS, 2010) John K; Fitzpatrick J; French N; Kazwala R; Kambarage D; Mfinanga GS; MacMillan A; Cleaveland SBackground Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. Methods This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA) test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. Results Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV) serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from livestock to humans. These can be achieved through health education to the communities where brucellosis is common.Item Using directed acyclic graphs to consider adjustment for socioeconomic status in occupational cancer studies.(B M J PUBLISHING GROUP, 2008-07) Richiardi L; Barone-Adesi F; Merletti F; Pearce NThere is an ongoing debate on whether analyses of occupational studies should be adjusted for socioeconomic status (SES). In this paper directed acyclic graphs (DAGs) were used to evaluate common scenarios in occupational cancer studies with the aim of clarifying this issue. It was assumed that the occupational exposure of interest is associated with SES and different scenarios were evaluated in which (a) SES is not a cause of the cancer under study, (b) SES is not a cause of the cancer under study, but is associated with other occupational factors that are causes of the cancer, (c) SES causes the cancer under study and is associated with other causal occupational factors. These examples illustrate that a unique answer to the issue of adjustment for SES in occupational cancer studies is not possible, as in some circumstances the adjustment introduces bias, in some it is appropriate and in others both the adjusted and the crude estimates are biased. These examples also illustrate the benefits of using DAGs in discussions of whether or not to adjust for SES and other potential confounders.Item Ian Prior and epidemiology in New Zealand.(B M J PUBLISHING GROUP, 2009-09) Pearce NIan Prior was born in Masterton, New Zealand, in 1923, and died in Wellington, New Zealand, in 2009. In 1959 Ian became the Director of the Medical Unit at Wellington Hospital, and in the early 1960s he established the Epidemiology Unit. Without doubt he is the founder of epidemiology in New Zealand, and has also had a major influence in Australia and further afield. I was delighted to be invited to write this piece about Ian for the Journal of Epidemiology and Community Health, not as an obituary but as an essay on an epidemiologist who inspired many of us in New Zealand, and whose example will continue to inspire many around the world. Ian Prior's work represents not only an important historical legacy but also an important guide to the future of epidemiology. This includes his work on the effects of social and environmental changes and the wider social context on individual "lifestyle", his willingness to work collaboratively with researchers from other disciplines including social scientists, his insistence on seeing quantitative biomedical phenomena (such as blood pressure) in the wider social context, and perhaps most of all his insistence that epidemiologists cannot hide from the wider realities of the world in which they live.Item Epidemiology in Latin America: an opportunity for a global dialogue.(B M J PUBLISHING GROUP, 2008-09) Pearce NNoneItem The association between retinal vein ophthalmodynamometric force change and optic disc excavation(British Medical Journal, 2009) Morgan WH; Hazelton ML; Balaratnasingamm C; Chan H; House PH; Barry CJ; Cringle SJ; Yu DAim: Retinal vein ophthalmodynamometric force (ODF) is predictive of future optic disc excavation in glaucoma, but it is not known if variation in ODF affects prognosis. We aimed to assess whether a change in ODF provides additional prognostic information. Methods: 135 eyes of 75 patients with glaucoma or being glaucoma suspects had intraocular pressure (IOP), visual fields, stereo optic disc photography and ODF measured on an initial visit and a subsequent visit at mean 82 (SD 7.3) months later. Corneal thickness and blood pressure were recorded on the latter visit. When venous pulsation was spontaneous, the ODF was recorded as 0 g. Change in ODF was calculated. Flicker stereochronoscopy was used to determine the occurrence of optic disc excavation, which was modelled against the measured variables using multiple mixed effects logistic regression. Results: Change in ODF (p = 0.046) was associated with increased excavation. Average IOP (p = 0.66) and other variables were not associated. Odds ratio for increased optic disc excavation of 1.045 per gram ODF change (95% CI 1.001 to 1.090) was calculated. Conclusion: Change in retinal vein ODF may provide additional information to assist with glaucoma prognostication and implies a significant relationship between venous change and glaucoma patho-physiology.Item Survival disparities in indigenous and non-indigenous New Zealanders with colon cancer: The role of patient comorbidity, treatment and health service factors(BMJ Publishing Group Ltd, 2010) Hill S; Sarfati D; Blakely T; Robson B; Purdie G; Chen J; Dennett E; Cormack D; Cunningham R; Dew K; McCreanor T; Kawachi IBackground Ethnic disparities in cancer survival have been documented in many populations and cancer types. The causes of these inequalities are not well understood but may include disease and patient characteristics, treatment differences and health service factors. Survival was compared in a cohort of Maori (Indigenous) and non-Maori New Zealanders with colon cancer, and the contribution of demographics, disease characteristics, patient comorbidity, treatment and healthcare factors to survival disparities was assessed. Methods Maori patients diagnosed as having colon cancer between 1996 and 2003 were identified from the New Zealand Cancer Registry and compared with a randomly selected sample of non-Maori patients. Clinical and outcome data were obtained from medical records, pathology reports and the national mortality database. Cancer-specific survival was examined using Kaplan�Meier survival curves and Cox hazards modelling with multivariable adjustment. Results 301 Maori and 328 non-Maori patients with colon cancer were compared. Maori had a significantly poorer cancer survival than non-Maori (hazard ratio (HR)=1.33, 95% CI 1.03 to 1.71) that was not explained by demographic or disease characteristics. The most important factors contributing to poorer survival in Maori were patient comorbidity and markers of healthcare access, each of which accounted for around a third of the survival disparity. The final model accounted for almost all the survival disparity between Maori and non-Maori patients (HR=1.07, 95% CI 0.77 to 1.47).Item Characteristics of ovarian cancer in women residing in Aotearoa, New Zealand: 1993-2004(BMJ Journals, 2009) Firestone RT; Wong KC; Ellison Loschmann EA; Pearce NE; Jeffreys MBackground: Few studies have compared ovarian cancer rates between different ethnic groups in the same country. The aim of this study was to describe ethnic patterns in the incidence and mortality of ovarian cancer in New Zealand, and to investigate ethnic and socioeconomic differences in the grade and stage of ovarian cancer. Methods: Data on all women registered with ovarian cancer on the New Zealand Cancer Registry (1993-2004) were analysed. Population data were taken from the 1996 and 2001 census. Logistic regression was used to estimate associations between ethnicity, deprivation and tumour characteristics. Results: Age-standardised incidence rates were highest in Pacific women, intermediate in Māori women, and lowest in non-Māori, non-Pacific women. Age-standardised mortality rates showed the same pattern. Ovarian cancer subtypes differed by ethnic group. There was no significant association between socioeconomic deprivation and tumour grade or stage. Age-adjusted models showed that Māori women were more likely to have well-differentiated tumours and less likely to present at a later stage compared to non-Māori, non-Pacific women. These patterns were partly explained by socioeconomic deprivation, and were not apparent for Pacific women. Conclusions: Pacific and Māori women experience higher incidence of ovarian cancer and mortality, compared to non-Māori, non-Pacific women. Māori women seemed to have better prognostic factors (local stage and well-differentiated tumours) than non-Māori, non-Pacific women. More work is needed to improve current cancer prevention strategies, particularly in Pacific women.Item Resiliency, Connectivity and Environments: Their roles in theorizing approaches to the promoting the wellbeing of young people(Clifford Beers Foundation, 2004-02) McCreanor, Tim; Watson, PeterEarly theory and findings in the area of resilience among young people emphasised individual differences and personality characteristics to explain different reactions to stress and risk. The ‘modern’ resiliency literature views the possible explanatory variables for different outcomes in broader contexts such as family, schools and community. Despite this change over time the individualising, problem focused orientation of resilience approaches continues to obscure the environment, leaving it an under-interrogated factor in youth wellbeing. The importance of this rests on its impact on policy and practice in the fields of youth development and health promotion. In this paper we argue that contemporary resiliency theory and research continue to fall short of the paradigm shift called for by those orienting to environmentally-based public health measures to improve population level wellbeing among young people.Item Youth identity formation and contemporary alcohol marketing(Taylor & Francis, 2005) McCreanor TN; Greenaway A; Moewaka Barnes HE; Borell SS; Gregory MJThis paper considers linkages between contemporary marketing theory and practice, and emerging conceptualizations of identity, to discuss implications for public health concerns over alcohol use among young people. Particular attention is paid to the theorizing of consumption as a component of youth identities and the ways in which developments of marketing praxis orients to such schemata. The authors' analyses of exemplars of marketing materials in use in Aotearoa New Zealand, drawn from their research archive, emphasize the sophistication and power of such forms of marketing. They argue that public health policy and practice must respond to the interweaving of marketing and the self-making practices of young people to counter this complex threat to the health and well-being of young people. © 2005 Taylor & Francis.