96,019 results

  • Factors associated with depression in patients referred to headache specialists.

    Jelinski, SE; Magnusson, Jane; Becker, WJ (2007)

    Journal article
    The University of Auckland Library

    Objective: To evaluate the relationship between selected demographic characteristics and clinical features in patients with headache and depression. Methods: We studied demographic and clinical data collected at the time of consultation for 712 new patients with headache referred to five headache specialty clinics in Canada. Data were analyzed as part of the Canadian Headache Outpatient Registry and Database (CHORD) Project. The Beck Depression Inventory (BDI-II) was used to identify the presence of depression. Multivariable logistic regression analysis was employed to evaluate associations between age, gender, employment status, marital status, diagnosis, headache days per month, medication overuse, headache impact (HIT-6), and headache disability (MIDAS) and the presence of depression as measured by the BDI-II. Results: Among the sample of patients with headache, 27% (n = 189) had moderate to severe depression. Factors independently associated with depression included age less than 50 years, being unemployed, being on disability pension or welfare, being widowed, separated, or divorced, a diagnosis of transformed migraine or headache associated with head trauma or cervical spine disorder, and showing severe headache impact as measured by the HIT-6, or severe disability as measured by the MIDAS. Conclusions: In patients with headache referred for specialist consultation, depression is strongly associated with being on disability or welfare, unemployment, age under 50 years, showing severe headache impact on the Headache Impact Test???6, and receiving a diagnosis of transformed migraine. The possibility of a concomitant depression should be strongly considered in patients with headache with any of these characteristics.

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  • Visibility of traffic control devices - catering for the real observer

    Johnston, AW; Cole, BL; Jacobs, Robert; Gibson, AJ (1976)

    Journal article
    The University of Auckland Library

    This paper reviews the visual characteristics of the ??? real ??? observer using both conventional methods of assessment and an information theory approach. Recent research by the authors and their colleagues on the acquisition of information by observers with normal and degraded vision shows that present scales for specifying visual performance do not adequately represent the visual requirements of many practical tasks These studies also suggest that there should be a. more systematic approach to the development of design rules based on visual performance characteristics of the whole user population rather than only that proportion of the population which has normal vision. Equally there should be a more purposeful and systematic approach to the imposition of minimum visual standards to ensure that observers maintain a level of visual capability adequate for the designed task.

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  • The Politics of Technological Upgrading in South Korea: How Government and Business Challenged the Might of Qualcomm

    Kim, Sung-Young (2012)

    Journal article
    The University of Auckland Library

    How has industrial restructuring and technological upgrading in South Korea undertaken in the post-crisis era impacted on the state???s capacity to guide strategic industry development? The latest reincarnation of the ???end of the developmental state??? thesis proposes that industry policies are losing their strategic long-term oriented character due to the state???s lack of legitimacy to play a guiding role after the economic recovery. I test this view in light of the Korean state???s role, since the early 2000s, in the promotion of a new mobile communications software standard known as the Wireless Internet Platform for Interoperability (WIPI). I argue that the Korean state retains a strategic long-term approach to techno-industrial governance. The argument is developed through examining how bureaucratic actors gained the legitimacy to challenge Qualcomm, the strategy involved in promoting WIPI, and how the bureaucracy supported domestic firms under an increasingly open international trading environment. The findings reveal the state???s ability to renew its legitimacy to play a developmental role through rearticulating policy goals from catching-up to nurturing innovation. Furthermore, the state has experimented with new forms of cooperation between government and business to nurture the growth of new infant technological growth sectors such as telecommunications.

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  • Synthesis of lithium corrole and its use as a reagent for the preparation of cyclopentadienyl zirconium and titanium corrole complexes

    Buckley, HL; Chomitz, WA; Koszarna, B; Tasior, M; Gryko, DT; Brothers, Penelope; Arnold, J (2012)

    Journal article
    The University of Auckland Library

    The lithium corrole complex (Mes (p-OMePh)corrole)Li ??6THF (1??6THF), prepared via deprotonation of the free-base corrole with lithium amide, acts as precursor for the preparation of cyclopentadienyl zirconium(iv) corrole (2) and pentamethylcyclopentadienyl titanium(iv) corrole (3).

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  • The synthesis, reactivity, and peripheral functionalization of corroles

    Lemon, CM; Brothers, Penelope (2011-09)

    Journal article
    The University of Auckland Library

    Corroles are unusual macrocycles that often exhibit chemical reactivity that is distinct from their closely related porphyrin cousins. Standard organic transformations with corroles often result in the formation of unexpected products. A survey of synthetic methods for the preparation of both meso-substituted and ??-substituted corroles will give an overview of the different synthetic strategies. This review provides a comprehensive description of the chemical reactivity and functionalization of corroles, focusing especially on reactions at the periphery of the macrocycle. Formylation, nitration, bromination and chlorosulfonation reactions will be explored in detail. In addition, demetalation processes, reactivity of the N-pyrrolic nitrogens and the lability of the macrocycle ring toward expansion and ring-opening reactions will be discussed. Finally, the synthesis of super-structured (picket-fence, capped, and strapped) corroles and isocorroles will be surveyed.

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  • Solution business models: Transformation along four continua

    Storbacka, Kaj; Windahl, Charlotta; Nenonen, Suvi; Salonen, A (2013-07)

    Journal article
    The University of Auckland Library

    Using a business model perspective, we identify four continua that are of specific relevance for industrial firms transforming toward solution business models: customer embeddedness, offering integratedness, operational adaptiveness, and organizational networkedness. Using these continua, we explore the opportunities and challenges related to solution business model development in two different business logics that are of particular importance in an industrial context: 'installed-base' (IB) and 'input-to-process' (I2P). The paper draws on eight independent research projects, spanning an eleven-year period, involving a total of 52 multinational enterprises. The findings show that the nature and importance of the continua differ between the I2P and IB business logics. IB firms can almost naturally transition toward solutions, usually through increasing customer embeddedness and offering integratedness, and then by addressing issues around the other continua. For I2P firms, the changes needed are less transitional. Rather, they have to completely change their mental models and address the development needs on all continua simultaneously.

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  • Growth in the neonatal period after repeat courses of antenatal corticosteroids: data from the ACTORDS randomised trial

    Battin, Malcolm; Bevan, C; Harding, Jane (2012-03)

    Journal article
    The University of Auckland Library

    Objective To determine the effect of repeated antenatal corticosteroids on postnatal changes in weight, linear growth and head circumference. Methods Mothers who entered the repeated dose of antenatal steroids (ACTORDS) trial were randomised to additional weekly steroid or placebo. Infant occipital-frontal head circumference, weight and crown-heel length were measured at birth and weekly for 4 weeks or until discharge, whichever was later. Lower leg length was measured using a knemometer daily for the first week, then thrice weekly. Results Of 145 babies studied (77.5% of the ACTORDS study infants from this centre), 70 were exposed to repeated antenatal steroids and 75 to placebo. There were no significant differences in prerandomisation demographic and pregnancy data. The mean gestational age at ACTORDS entry was 28.7 weeks and at birth was 31.4 weeks. The mean birth weight was 1618 g. There were no significant differences in postmenstrual age, weight, length or head circumference, nor in z-scores for these measurements, at birth, 4 weeks or discharge. In the first 2 weeks after birth, babies in both groups showed a decrease in z-scores for weight and length. After week 2, growth improved in both groups but babies exposed to repeat antenatal corticosteroids grew more rapidly, as measured by weight gain, increasing head circumference and increasing lower leg length knemometry. This rapid growth was most apparent around weeks 3???5 after birth. Conclusion Babies exposed to weekly doses of repeat antenatal corticosteroids demonstrate postnatal growth acceleration 3???5 weeks after birth.

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  • Extent of palliative care need in the acute hospital setting: a survey of two acute hospitals in the UK

    Gardiner, Clare; Gott, Caryl; Ingleton, C; Seymour, J; Cobb, M; Noble, B; Bennett, M; Ryan, T (2013-01)

    Journal article
    The University of Auckland Library

    Background: In common with international health policy, The End of Life Care Strategy for England has highlighted the delivery of high quality palliative care in the acute hospital setting as an area of priority. Aim: The aim of this study was to explore the extent of palliative care need in the acute hospital setting, and to explore agreement between different sources in the identification of patients with palliative care need. Design: A cross-sectional survey of palliative care need was undertaken in two UK acute hospitals. Hospital case notes were examined for evidence of palliative care need according to Gold Standards Framework (GSF) prognostic indicator criteria. Medical and nursing staff were asked to identify patients with palliative care needs. Patients (or consultees) completed assessments of palliative care need. Participants: Of a total in-patient population of 1359, complete datasets were collected for 514 patients/consultees. Results: 36.0% of patients were identified as having palliative care needs according to GSF criteria. Medical staff identified 15.5% of patients as having palliative care needs, and nursing staff 17.4% of patients. Patient self-report data indicated that 83.2% of patients meeting GSF criteria had palliative care needs. Conclusion: The results reveal that according to the GSF prognostic guide, over a third of hospital in-patients meet the criteria for palliative care need. Consensus between medical staff, nursing staff and the GSF was poor regarding the identification of patients with palliative care needs. This has significant implications for patient care, and draws into question the utility of the GSF in the hospital setting.

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  • Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation?

    James, JL; Chamley, Lawrence; Carter, AM (2012-05)

    Journal article
    The University of Auckland Library

    The implantation of the blastocyst and early development of the placenta are crucial for the success of implantation and pregnancy. However, the formative stages of human placental development are largely unknown because of their existence in a 'black box' where access to samples is extremely limited for ethical reasons. In this review we discuss our current knowledge of early placental formation from the time of implantation at 3 weeks of gestation to approximately 5-6 weeks of gestation, encompassing both the significant anatomical findings derived from the unique specimens obtained in the mid-20th century and the renewed study of this period over the past 10 years as novel models of implantation have been developed. ?? 2012 Elsevier Ltd. All rights reserved.

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  • Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): A randomised, double-blind, placebo-controlled trial

    Harris, Deborah; Weston, PJ; Signal, M; Chase, JG; Harding, Jane (2013)

    Journal article
    The University of Auckland Library

    Background: Neonatal hypoglycaemia is common, and a preventable cause of brain damage. Dextrose gel is used to reverse hypoglycaemia in individuals with diabetes; however, little evidence exists for its use in babies. We aimed to assess whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. Methods: We undertook a randomised, double-blind, placebo-controlled trial at a tertiary centre in New Zealand between Dec 1, 2008, and Nov 31, 2010. Babies aged 35-42 weeks' gestation, younger than 48-h-old, and at risk of hypoglycaemia were randomly assigned (1:1), via computer-generated blocked randomisation, to 40% dextrose gel 200 mg/kg or placebo gel. Randomisation was stratified by maternal diabetes and birthweight. Group allocation was concealed from clinicians, families, and all study investigators. The primary outcome was treatment failure, defined as a blood glucose concentration of less than 2??6 mmol/L after two treatment attempts. Analysis was by intention to treat. The trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12608000623392. Findings: Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 [14%] vs 29 [24%]; relative risk 0??57, 95% CI 0??33-0??98; p=0??04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0??9 mmol/L. No other adverse events took place. Interpretation: Treatment with dextrose gel is inexpensive and simple to administer. Dextrose gel should be considered for first-line treatment to manage hypoglycaemia in late preterm and term babies in the first 48 h after birth. Funding: Waikato Medical Research Foundation, the Auckland Medical Research Foundation, the Maurice and Phyllis Paykel Trust, the Health Research Council of New Zealand, and the Rebecca Roberts Scholarship.

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  • A collaborative resource to build consensus for automated left ventricular segmentation of cardiac MR images.

    Suinesiaputra, Avan; Cowan, Brett; Al-Agamy, AO; Elattar, MA; Ayache, N; Fahmy, AS; Khalifa, AM; Medrano Gracia, Pau; Jolly, MP; Kadish, AH; Lee, DC; Margeta, J; Warfield, SK; Young, Alistair (2014-01)

    Journal article
    The University of Auckland Library

    A collaborative framework was initiated to establish a community resource of ground truth segmentations from cardiac MRI. Multi-site, multi-vendor cardiac MRI datasets comprising 95 patients (73 men, 22 women; mean age 62.73??11.24years) with coronary artery disease and prior myocardial infarction, were randomly selected from data made available by the Cardiac Atlas Project (Fonseca et al., 2011). Three semi- and two fully-automated raters segmented the left ventricular myocardium from short-axis cardiac MR images as part of a challenge introduced at the STACOM 2011 MICCAI workshop (Suinesiaputra et al., 2012). Consensus myocardium images were generated based on the Expectation-Maximization principle implemented by the STAPLE algorithm (Warfield et al., 2004). The mean sensitivity, specificity, positive predictive and negative predictive values ranged between 0.63 and 0.85, 0.60 and 0.98, 0.56 and 0.94, and 0.83 and 0.92, respectively, against the STAPLE consensus. Spatial and temporal agreement varied in different amounts for each rater. STAPLE produced high quality consensus images if the region of interest was limited to the area of discrepancy between raters. To maintain the quality of the consensus, an objective measure based on the candidate automated rater performance distribution is proposed. The consensus segmentation based on a combination of manual and automated raters were more consistent than any particular rater, even those with manual input. The consensus is expected to improve with the addition of new automated contributions. This resource is open for future contributions, and is available as a test bed for the evaluation of new segmentation algorithms, through the Cardiac Atlas Project (www.cardiacatlas.org).

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  • A novel air flow sensor from printed PEDOT micro-hairs

    Parcell, James; Aydemir, N; Devaraj, Harish; Travas-Sejdic, Jadranka; Williams, David; Aw, Kean (2013)

    Journal article
    The University of Auckland Library

    We report the creation of a low flow rate sensor from PEDOT micro-hairs. The hairs are printed as pipette-defined depositions using a nanopositioning system. The printing technique was developed for fabricating structures in 2D and 3D. Here micro-hairs with diameters of 4.4 ??m were repeatedly extruded with constant heights. These hairs were then applied to produce a prototype flow rate sensor, which was shown to detect flows of 3.5 l min ???1 . Structural analysis was performed to demonstrate that the design can be modified to potentially observe flows as low as 0.5 l min ???1 . The results are extended to propose a practical digital flow rate sensor.

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  • Validation of low-cost ozone measurement instruments suitable for use in an air-quality monitoring network

    Williams, David; Henshaw, GS; Bart, M; Laing, G; Wagner, J; Naisbitt, S; Salmond, Jennifer (2013-06)

    Journal article
    The University of Auckland Library

    This paper presents a novel low-cost instrument that uses a sensor based on conductivity changes of heated tungstic oxide, which is capable of accurately measuring ambient concentrations of ozone. A combination of temperature steps and air flow-rate steps is used to continually reset and re-zero the sensor. A two-stage calibration procedure is presented, in which a nonlinear transformation converts sensor resistance to a signal linear in ozone concentration, then a linear correlation is used to align the calibration with a reference instrument. The required calibration functions specific for the sensor, and control system for air flow rate and sensor temperature, are housed with the sensor in a compact, simple-to-exchange assembly. The instrument can be operated on solar power and uses cell phone technology to enable monitoring in remote locations. Data from field trials are presented here to demonstrate that both the accuracy and the stability of the instrument over periods of months are within a few parts-per-billion by volume. We show that common failure modes can be detected through measurement of signals available from the instrument. The combination of long-term stability, self-diagnosis, and simple, inexpensive repair means that the cost of operation and calibration of the instruments is significantly reduced in comparison with traditional reference instrumentation. These instruments enable the economical construction and operation of ozone monitoring networks of accuracy, time resolution and spatial density sufficient to resolve the local gradients that are characteristic of urban air pollution.

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  • Stand Structure and Aboveground Biomass of a Pelliciera rhizophorae Mangrove Forest, Gulf of Monitjo Ramsar Site, Pacific Coast, Panama

    Gross, J; Flores, E; Schwendenmann, Luitgard (2014)

    Journal article
    The University of Auckland Library

    Mangroves provide several ecosystems services including carbon storage. Aboveground biomass as a proxy for carbon storage and stand structure were investigated in nine plots located in a riverine Pelliciera rhizophorae forest, Gulf of Montijo Ramsar Site, Pacific Coast, Panama. Aboveground biomass for all trees above 2 cm was estimated using common pan-tropical mangrove biomass regression models. Despite a comparatively low tree species diversity there was a considerable variation in stand structure and biomass among the plots. P. rhizophorae dominated the river and center plots with tree densities between 1,275 and 10,075 trees ha???1. Further inland, species composition shifted towards a Rhizophora racemosa dominated forest. Lower density of larger trees in the inland plots may be due to small-scale cutting of trees at the forest margin. Across all plots, P. rhizophorae was smaller in diameter and height than R. racemosa. Aboveground biomass ranged from 76 Mg ha???1 to 335 Mg ha???1 (average: 176 Mg ha???1) and was closely related to stem density and basal area. Compared to other neotropical mangrove forests this riverine P. rhizophorae forest stores substantial amounts of biomass. Conservation strategies have to be put in place to maintain the threatened P. rhizophorae forest in Central America.

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  • Fetal growth factors and fetal nutrition

    Bloomfield, Francis; Spiroski, Ana-Mishel; Harding, Jane (2013)

    Journal article
    The University of Auckland Library

    Optimal fetal growth is important for a healthy pregnancy outcome and also for lifelong health. Fetal growth is largely regulated by fetal nutrition, and mediated via the maternal and fetal glucose/insulin/insulin-like growth factor axes. Fetal nutrition may reflect maternal nutrition, but abnormalities of placental function can also affect fetal growth, as the placenta plays a key intermediary role in nutritional signalling between mother and fetus. Fetal nutrition also impacts on the development of key fetal endocrine systems such as the glucose-insulin and insulin-like growth factor axes. This is likely to contribute to the link between both fetal growth restriction and fetal overgrowth, and increased risks of obesity and impaired glucose tolerance in later life. This review focuses on the associations between maternal and fetal nutrition, fetal growth and later disease risk, with particular emphasis on the role of insulin-like growth factors and the importance of the periconceptional period.

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  • High pressure processing (HPP) of honey for the improvement of nutritional value

    Akhmazillah, MFN; Farid, Mohammed; Oliveira, Maria (2013-10)

    Journal article
    The University of Auckland Library

    The present study was undertaken to assess the effect of high pressure processing (HPP) on total phenolic content (TPC) in manuka honey. Manuka honey is known for its amazing antimicrobial action and antioxidant properties. The effect of HPP (200, 400 and 600 MPa) at ambient and moderate temperatures (53.41 ?? 0.30 ??C, 65.29 ?? 1.77 ??C, 71.92 ?? 1.63 ??C) and their combination for different processing time (5, 10 and 15 min) was investigated. Conventional thermal processing (51.74 ?? 0.03 ??C, 61.90 ?? 0.10 ??C and 71.58 ?? 0.04 ??C) was also carried out as comparison to HPP. Operating HPP at 600 MPa (26.80 ?? 0.95 ??C-30.18 ?? 2.14 ??C) for 10 min was found to be the most effective process with 47.16% increment in TPC as compared to unprocessed honey, whereas no significant increase (p < 0.05) was observed in thermal processing as well as in combined HPP-thermal processing. Therefore, HPP at ambient temperatures could be an appropriate method to produce tastier and more nutritive manuka honey. Industrial relevance: The preservation of total phenolic content (TPC) as a main phytochemical component in honey is very important with direct impact on nutritional value and antioxidant activity. A significant increase in the TPC was obtained by processing. Results demonstrated the HPP capability to increase TPC in manuka honey by 47%. From a nutritional perspective, this result is associated with the production of a higher antioxidant honey, known to prevent certain diseases such as cancer. The study generates a new approach in honey processing which can guarantee the high nutritional quality of honey and its original natural freshness. ?? 2013 Elsevier Ltd. All rights reserved.

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  • A new lupene triterpenetriol and anticholinesterase activity of Salvia sclareoides

    Rauter, AP; Branco, I; Lopes, RG; Justino, J; Oliveira, Maria; Noronha, JP; Cabrita, EJ; Brouard, I; Bermejo, J (2007-12)

    Journal article
    The University of Auckland Library

    A new lupene triterpenetriol was isolated from the acetone extract of the aerial parts of Salvia sclareoides and characterised as (1??,3??)-lup-20(29)-ene-1,3,30-triol (1). In addition, nepetidin (2), nepeticin (3), lupendiol (4), (1??,11??)-dihydroxy-lup-20(29)-en-3-one (5), ursolic acid (6), sumaresinolic acid (7) and hederagenin (8), were identified in this Salvia sp. To the best of our knowledge, the compounds 2 and 7 are new constituents in Salvia spp. The acetone, ethanol, butanol and water extracts of the plant were screened for the in vitro inhibitory activity of acetylcholinesterase (AChE) and butyrilcholinesterase (BChE), enzymes which play a role in the Alzheimer disease. All extracts inhibited acetylcholinesterase activity at 10????g/ml, a remarkable activity since the standard drug rivastigmine does not inhibit acetylcholinesterase at the same concentration. Regarding the butyrilcholinesterase, the acetone extract at 1000????g/ml was able to inhibit completely the enzyme activity and the butanol and ethanol extracts, at this concentration, produced a potent inhibition of BchE. ?? 2007 Elsevier B.V. All rights reserved.

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  • Alicyclobacillus acidoterrestris spores in fruit products and design of pasteurization processes

    Oliveira, Maria; Gibbs, P (2001-02-01)

    Journal article
    The University of Auckland Library

    Alicyclobacillus acidoterrestris is a thermoacidophilic, non-pathogenic and sporeforming bacterium which has been found in commercial pasteurized fruit juices in the past. Only few and recent studies were available in the literature, since only in 1984 Cerny et al. [Cerny, G., Hennlich, W., & Poralla, K. (1984). Fruchtsaftverderb durch bacillen: isolierung und charakterisierung des verderbserregers. Z. Lebensmitt. Unters. Forsch. 179, 224-227] reported a spoiled aseptically packaged apple juice with A. acidoterrestris and in 1987 Deinhard et al. [Deinhard, G., Blanz, P., Poralla, K., & Altan, E. (1987). Bacillus acidoterrestris sp. nov., a new thermotolerant acidophile isolated from different soils. Systematic and Applied Microbiology, 10, 47-53] named first this species. Detection and identification methods for A. acidoterrestris were reviewed and data regarding heat resistance of spores and growth in fruits were collected. Finally, a new methodology to design pasteurization processes for high acidic fruit products is presented.

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  • Rapid construction of a patient specific torso model from 3D ultrasound for noninvasive imaging of cardiac electrophysiology

    Cheng, Leo; Sands, Gregory; French, RL; Withy, SJ; Wong, SP; Legget, Malcolm; Smith, WM; Pullan, Andrew (2005)

    Journal article
    The University of Auckland Library

    One of the main limitations in using inverse methods for non-invasively imaging cardiac electrical activity in a clinical setting is the difficulty in readily obtaining high-quality data sets to reconstruct accurately a patient-specific geometric model of the heart and torso. This issue was addressed by investigation into the feasibility of using a pseudo-3D ultrasound system and a hand-held laser scanner to reconstruct such a model. This information was collected in under 20 min prior to a catheter ablation or pacemaker study in the electrophysiology laboratory. Using the models created from these data, different activation field maps were computed using several different inverse methods. These were independently validated by comparison of the earliest site of activation with the physical location of the pacing electrodes, as determined from orthogonal fluoroscopy images. With an estimated average geometric error of approximately 8 mm, it was also possible to reconstruct the site of initial activation to within 17.3 mm and obtain a quantitatively realistic activation sequence. The study demonstrates that it is possible rapidly to construct a geometric model that can then be used non-invasively to reconstruct an activation field map of the heart.

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  • Identification of a pathway by which glucose regulates ??-catenin signalling via the cAMP/protein kinase A pathway in ??-cell models.

    Cognard, Emmanuelle; Dargaville, CG; Hay, Deborah; Shepherd, Peter (2013-02-01)

    Journal article
    The University of Auckland Library

    Pancreatic ??-cells are highly responsive to changes in glucose, but the mechanisms involved are only partially understood. There is increasing evidence that the ??-catenin signalling pathway plays an important role in regulating ??-cell function, but the mechanisms regulating ??-catenin signalling in these cells is not well understood. In the present study we show that ??-catenin levels and downstream signalling are regulated by changes in glucose levels in INS-1E and ??-TC6-F7 ??-cell models. We found a glucose-dependent increase in levels of ??-catenin in the cytoplasm and nucleus of INS-1E cells. Expression of cyclin D1 also increased with glucose and required the presence of ??-catenin. This was associated with an increase in phosphorylation of ??-catenin on Ser552, which is known to stabilize the molecule and increase its transcriptional activity. In a search for possible signalling intermediates we found forskolin and cell-permeable cAMP analogues recapitulated the glucose effects, suggesting a role for cAMP and PKA (cAMP-dependent protein kinase/protein kinase A) downstream of glucose. Furthermore, glucose caused sustained increases in cAMP. Two different inhibitors of adenylate cyclase and PKA signalling blocked the effects of glucose, whereas siRNA (small interfering RNA) knockdown of PKA blocked the effects of glucose on ??-catenin signalling. Finally, reducing ??-catenin levels with either siRNA or pyrvinium impaired glucose- and KCl-stimulated insulin secretion. Taken together the results of the present study define a pathway by which changes in glucose levels can regulate ??-catenin using a mechanism which involves cAMP production and the activation of PKA. This identifies a pathway that may be important in glucose-dependent regulation of gene expression and insulin secretion in ??-cells.

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