Field Work Reflections: Journeys in Knowing and Not-Knowing

In this paper, I retrace my interest in narrative forms of inquiry. I begin by revisiting a series of research projects that I conducted early in my career, describing some of my own dissatisfactions with the methods I used at the time. I move on to a detailed reexamination of my first piece of narrative research, completed during my PhD. In that project I used a narrative pointed psychosocial method in an attempt to develop new knowledge in the field of drugs, ‘race’ and ethnicity. In the final section, I consider what I have learned from this approach in terms of knowing and not-knowing and how I have used this experience to explore different approaches to narrative inquiry. I finish by drawing out some lessons I have learned from these different studies, which I hope might be of relevance to other social work researchers

Epigallocatechin-3-gallate remodels apolipoprotein A-I amyloid fibrils into soluble oligomers in the presence of heparin

Amyloid deposits of wild-type apolipoprotein A-I (apoA-I), the main protein component of high-density lipoprotein, accumulate in atherosclerotic plaques where they may contribute to coronary artery disease by increasing plaque burden and instability. Using CD analysis, solid-state NMR spectroscopy, and transmission EM, we report here a surprising cooperative effect of heparin and the green tea polyphenol (-)- epigallocatechin-3-gallate (EGCG), a known inhibitor and modulator of amyloid formation, on apoA-I fibrils. We found that heparin, a proxy for glycosaminoglycan (GAG) polysaccharides that co-localize ubiquitously with amyloid in vivo, accelerates the rate of apoA-I formation from monomeric protein and associates with insoluble fibrils. Mature, insoluble apoA-I fibrils bound EGCG (KD = 30 ± 3 μM; Bmax = 40 ± 3 μM), but EGCG did not alter the kinetics of apoA-I amyloid assembly from monomer in the presence or absence of heparin. EGCG selectively increased the mobility of specific backbone and side-chain sites of apoA-I fibrils formed in the absence of heparin, but the fibrils largely retained their original morphology and remained insoluble. By contrast, fibrils formed in the presence of heparin were mobilized extensively by the addition of equimolar EGCG, and the fibrils were remodeled into soluble 20-nm-diameter oligomers with a largely α-helical structure that were nontoxic to human umbilical artery endothelial cells. These results argue for a protective effect of EGCG on apoA-I amyloid associated with atherosclerosis and suggest that EGCG-induced remodeling of amyloid may be tightly regulated by GAGs and other amyloid co-factors in vivo, depending on EGCG bioavailability

Groundwater residence time in the Kulnura-Mangrove Mountain Plateau (Gosford, NSW, Australia)

The Kulnura-Mangrove Mountain plateau consists of the catchments of Mangrove, Narara, Mooney Mooney, and Ourimbah Creeks, and Wyong River. Groundwater plays a key role in sustaining stream flow within these catchments. Estimates indicate up to 50% of annual stream flow is derived from baseflow. The local community water supply relies on the groundwater within the elevated Hawkesbury- Narrabeen sandstone plateau. Furthermore, the Gosford-Wyong Councils’ Water Authority (WSA) is the third largest in NSW and utilises many of the streams flowing from the sandstone plateau for municipal water supply. It is anticipated that the WSA will provide municipal water for 319 000 persons by the year 2010. The increasing volumes of groundwater being extracted and changing land use have the potential to cause damage to the fresh water aquifer through contamination and aquifer depletion. A hydrogeochemical survey (2006-2009) has been conducted in NSW Dept of Water and Energy (DWE) monitoring wells across the plateau in order to determine groundwater residence times. Groundwater was analysed for major ions, minor and trace elements, H2O 18O and 2H, 13CDIC, 87Sr/86Sr, 14CDIC, and 3H, and complemented with mineralogical and isotopic information obtained from soil and drill chips collected during well construction. Water stable isotopes confirm the meteoric origin of the groundwater with most values plotting on the local meteoric water line. Localised evaporative trends suggest recharge with evaporated groundwater stored in ponds. Shallow groundwaters have 3H and 14C activities consistent with modern recharge (Fig 1). Carbon “bomb pulse” signatures of up to 116.8 pmC are found in the central areas of the plateau. The thin soils, lack of carbonates in the intensely weathered near-surface Hawkesbury sandstone, and the shallow depth of the water samples is consistent with the 3H results measured, suggesting minimal dilution of the original 14C. Input of this data into a southern hemisphere bomb pulse model [1] suggest potential recharge during the 1990´s, coinciding with sustained wet conditions and above average rainfalls experienced during this period. Fig. 1. 14C vs 3H plot of groundwater samples in the Kulnura- Mangrove Mountain Plateau Deeper groundwaters have lower 14C and 3H activities in some cases close to background level (Fig. 1). The quantifiable 3H suggests residence times of <70 a. However, non-corrected 14C residence times are submodern (>500 a). This apparent discrepancy can be explained by either mixing with older waters or dissolution of carbonates. The good correlation of total dissolved inorganic carbon (TDIC) and Ca (R2=0.8), 13CTDIC in groundwater and mineralogy results from drill chips suggest that dissolution of dispersed carbonates is taking place. The deepest groundwaters show the most difference in residence time across the study area. The eastern and western plateaus yield old groundwater with 14C corrected residence times of around 9 ka and 4 ka respectively. However, the groundwater at equivalent depths in the central plateau was found to be considerably younger with residence times of <70 a

A comparison between direct and pan-derived measurements of the isotopic composition of atmospheric waters

The stable isotopes of water can be used to examine and quantify the contribution to atmospheric moisture from evaporation, transpiration and surface-waters. However, obtaining extensive and ongoing time series data of the isotopic composition of atmospheric moisture has been difficult. Presented here is an alternate method using an isotope mass balance approach to estimate the isotopic composition of atmospheric moisture using water samples collected from class A evaporation pans. While this evaporation pan method does not provide the high-resolution time series data that can be obtained from an isotope analyser taking in-situ measurements of atmospheric moisture, the method is relatively simple and inexpensive to set-up and maintain. In this preliminary investigation, a comparison between the isotopic composition of atmospheric moisture estimated from the evaporation pan method and in-situ measurements of the isotopic composition of water vapour using a Fourier Transform Infrared (FTIR) spectrometer deployed at the Lucas Heights weather station in New South Wales is undertaken. Through comparison of the two series of hydrogen isotope data, an assessment of the evaporation pan method can be made. Although there was some agreement between the isotopic composition of vapour measured by the FTIR spectrometer and the estimation for the atmospheric moisture (R2 = 0.49), the comparison is sensitive to climatic parameters that vary significantly within a 24-hour period such as the relative humidity of air and the air and pan temperatures. Inverting the model to use the FTIR spectrometer measurements at an hourly resolution improved the performance of the model (R2 =0.57). However, this also revealed that the model produced more depleted values of the evaporation pan water isotopes than those observed. In contrast, there was a variable relationship between the modelled and observed isotope values of atmospheric moisture. These conflicting results will need to be resolved before the evaporation pan method is broadly applied in isotope hydrology. © 2011 The Modelling and Simulation Society of Australia and New Zealand Inc

Prognostic microRNAs in high-grade glioma reveal a link to oligodendrocyte precursor differentiation.

MicroRNA expression can be exploited to define tumor prognosis and stratification for precision medicine. It remains unclear whether prognostic microRNA signatures are exclusively tumor grade and/or molecular subtype-specific, or whether common signatures of aggressive clinical behavior can be identified. Here, we defined microRNAs that are associated with good and poor prognosis in grade III and IV gliomas using data from The Cancer Genome Atlas. Pathway analysis of microRNA targets that are differentially expressed in good and poor prognosis glioma identified a link to oligodendrocyte development. Notably, a microRNA expression profile that is characteristic of a specific oligodendrocyte precursor cell type (OP1) correlates with microRNA expression from 597 of these tumors and is consistently associated with poor patient outcome in grade III and IV gliomas. Our study reveals grade-independent and subtype-independent prognostic molecular signatures in high-grade glioma and provides a framework for investigating the mechanisms of brain tumor aggressiveness

Demanding stories: television coverage of sustainability, climate change and material demand

This paper explores the past, present and future role of broadcasting, above all via the medium of television, in shaping how societies talk, think about and act on climate change and sustainability issues. The paper explores these broad themes via a focus on the important but relatively neglected issue of material demand and opportunities for its reduction. It takes the outputs and decision-making of one of the world’s most influential broadcasters, the BBC, as its primary focus. The paper considers these themes in terms of stories, touching on some of the broader societal frames of understanding into which they can be grouped. Media decision-makers and producers from a range of genres frequently return to the centrality of ‘story’ in the development, commissioning and production of an idea. With reference to specific examples of programming, and drawing on interviews with media practitioners, the paper considers the challenges of generating broadcast stories that can inspire engagement in issues around climate change, and specifically material demand. The concluding section proposes actions and approaches that might help to establish material demand reduction as a prominent way of thinking about climate change and environmental issues more widely. This article is part of the themed issue ‘Material demand reduction’

Vigorous star formation hidden by dust in a galaxy at z=1.4z=1.4

Near-infrared surveys have revealed a substantial population of enigmatic faint galaxies with extremely red optical-to-near-infrared colours and with a sky surface density comparable to that of faint quasars. There are two scenarios for these extreme colours: (i) these distant galaxies have formed virtually all their stars at very high redshifts and, due to the absence of recently formed stars, the colours are extremely red and (ii) these distant galaxies contain large amounts of dust, severely reddening the rest-frame UV--optical spectrum. HR10 ($z = 1.44$) is considered the archetype of the extremely red galaxies. Here we report the detection of the continuum emission from HR10 at 850$\mu$m and at 1250$\mu$m, demonstrating that HR10 is a very dusty galaxy undergoing a major episode of star formation. Our result provides a clear example of a high-redshift galaxy where the star formation rate inferred from the ultraviolet luminosity would be underestimated by a factor up to 1000, and shows that great caution should be used to infer the global star formation history of the Universe from optical observations only.Comment: 12 pages, 1 figure, Nature, in press (30 April 1998

Two decades since the fetal insulin hypothesis: what have we learned from genetics?

This is the final version. Available from Springer via the DOI in this record. Data availability: This review did not generate any new data.In 1998 the fetal insulin hypothesis proposed that lower birthweight and adult-onset type 2 diabetes are two phenotypes of the same genotype. Since then, advances in research investigating the role of genetics affecting insulin secretion and action have furthered knowledge of fetal insulin-mediated growth and the biology of type 2 diabetes. In this review, we discuss the historical research context from which the fetal insulin hypothesis originated and consider the position of the hypothesis in light of recent evidence. In summary, there is now ample evidence to support the idea that variants of certain genes which result in impaired pancreatic beta cell function and reduced insulin secretion contribute to both lower birthweight and higher type 2 diabetes risk in later life when inherited by the fetus. There is also evidence to support genetic links between type 2 diabetes secondary to reduced insulin action and lower birthweight but this applies only to loci implicated in body fat distribution and not those influencing insulin resistance via obesity or lipid metabolism by the liver. Finally, we also consider how advances in genetics are being used to explore alternative hypotheses, namely the role of the maternal intrauterine environment, in the relationship between lower birthweight and adult cardiometabolic disease.Wellcome TrustNational Institute of Health Research (NIHR)Royal Societ

Therapeutic benefits of distal ventricular pacing in mid-cavity obstructive hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. METHODS: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. RESULTS: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: -70.86 to -40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: -37.19 to -13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1). CONCLUSION: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration

Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies

Background: The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention. Methods and Findings: To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, p < 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both p < 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both p < 0.001), high-density lipoprotein (correlation coefficient 0.16 and ?0.14, respectively; both p < 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both p < 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, p = 0.001) and lipoprotein(a) (correlation coefficient ?0.11, p < 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect. Conclusions: In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of APOE genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE