26,352 results for Journal article

  • Inventory Management Under Market Size Dynamics

    Olsen, Tava; Parker, RP (2008-10)

    Journal article
    The University of Auckland Library

    We investigate the situation where a customer experiencing an inventory stockout at a retailer potentially leaves the firm's market. In classical inventory theory, a unit stockout penalty cost has been used as a surrogate to mimic the economic effect of such a departure; in this study, we explicitly represent this aspect of consumer behavior, incorporating the diminishing effect of the consumers leaving the market upon the stochastic demand distribution in a time-dynamic context. The initial model considers a single firm. We allow for consumer forgiveness where customers may flow back to the committed purchasing market from a nonpurchasing "latent" market. The per-period decisions include a marketing mix to attract latent and new consumers to the committed market and the setting of inventory levels. We establish conditions under which the firm optimally operates a base-stock inventory policy. The subsequent two models consider a duopoly where the potential market for a firm is now the committed market of the other firm; each firm decides its own inventory level. In the first model, the only decisions are the stocking decisions and in the second model, a firm may also advertise to attract dissatisfied customers from its competitor's market. In both cases, we establish conditions for a base-stock equilibrium policy. We demonstrate comparative statics in all models. [ABSTRACT FROM AUTHOR]

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  • Cot-side electroencephalography monitoring is not clinically useful in the detection of mild neonatal hypoglycemia

    Harris, Deborah; Weston, PJ; Williams, CE; Pleasants, AB; Battin, Malcolm; Spooner, CG; Harding, Jane (2011)

    Journal article
    The University of Auckland Library

    Objectives To determine whether there is a relationship between electroencephalography patterns and hypoglycemia, by using simultaneous cot-side amplitude integrated electroencephalography (aEEG) and continuous interstitial glucose monitoring, and whether non-glucose cerebral fuels modi???ed these patterns. Study design Eligible babies were $32 weeks gestation, at risk for hypoglycemia, and admitted to the neonatal intensive care unit. Electrodes were placed in C3-P3, C4-P4 O1-O2 montages. A continuous interstitial glucose sensor was placed subcutaneously, and blood glucose was measured by using the glucose oxidase method. Non-glucose cerebral fuels were measured at study entry, exit, and during recognized hypoglycemia. Results A total of 101 babies were enrolled, with a median weight of 2179 g and gestation of 35 weeks. Twentyfour of the babies had aEEG recordings, and glucose concentrations were low (<2.6 mM). There were 103 episodes of low glucose concentrations lasting 5 to 475 minutes, but no observable changes in aEEG variables. Plasma concentrations of lactate, beta-hydroxybutyrate, and glycerol were low and did not alter during hypoglycemia. Conclusions Cot-side aEEG was not useful for the detection of neurological changes during mild hypoglycemia. Plasma concentrations of non-glucose cerebral fuels were low and unlikely to provide substantial neuroprotection.

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  • Myocardial material parameter estimation: a comparison of invariant based orthotropic constitutive equations

    Schmid, Holger; Wang, Yikan; Ashton, Jesse; Ehret, AE; Krittian, Sebastian; Nash, Martyn; Hunter, Peter (2009)

    Journal article
    The University of Auckland Library

    This study investigated a number of invariant based orthotropic and transversely isotropic constitutive equations for their suitability to fit three-dimensional simple shear mechanics data of passive myocardial tissue. A number of orthotropic laws based on Green strain components and one microstructurally based law have previously been investigated to fit experimental measurements of stress-strain behaviour. Here we extend this investigation to include several recently proposed functional forms, i.e. invariant based orthotropic and transversely isotropic constitutive relations. These laws were compared on the basis of (i) ???goodness of fit???: how well they fit a set of six shear deformation tests, (ii) ???variability???: how well determined the material parameters are over the range of experiments. These criteria were utilised to discuss the advantages and disadvantages of the constitutive laws. It was found that a specific form of the polyconvex type as well as the exponential Fung-type law from the previous study were most suitable for modelling the orthotropic behaviour of myocardium under simple shear.

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  • Coupling multi-physics models to cardiac mechanics

    Nordsletten, David; Niederer, SA; Nash, Martyn; Hunter, Peter; Smith, Nicolas (2011)

    Journal article
    The University of Auckland Library

    We outline and review the mathematical framework for representing mechanical deformation and contraction of the cardiac ventricles, and how this behaviour integrates with other processes crucial for understanding and modelling heart function. Building on general conservation principles of space, mass and momentum, we introduce an arbitrary EulerianeLagrangian framework governing the behaviour of both fluid and solid components. Exploiting the natural alignment of cardiac mechanical properties with the tissue microstructure, finite deformation measures and myocardial constitutive relations are referred to embedded structural axes. Coupling approaches for solving this large deformation mechanics framework with three dimensional fluid flow, coronary hemodynamics and electrical activation are described. We also discuss the potential of cardiac mechanics modelling for clinical applications.

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  • Enacting Clan Control in Complex IT Projects: A Social Capital Perspective

    Chua, Cecil; Lim, WK; Soh, C; Sia, SK (2012)

    Journal article
    The University of Auckland Library

    The information technology project control literature has documented that clan control is often essential in complex multistakeholder projects for project success. However, instituting clan control in such conditions is challenging as people come to a project with diverse skills and backgrounds. There is often insufficient time for clan control to develop naturally. This paper investigates the question, "How can clan control be enactedin complex IT projects?" Recognizing social capital as a resource, we conceptualize a clan as a group with strong social capital (i.e., where its members have developed their structural, cognitive, and relational ties to the point that they share common values and beliefs and are committed to a set of peer norms). We theorize that the enactment of clan control is a dual process of (1) building the clan by developing its social capital dimensions (structural, cognitive, and relational ties) or reappropriating social capital from elsewhere and(2) leveraging the clan by reinforcing project-facilitating shared values, beliefs, and norms, and inhibiting those that impede the achievement of project goals. We explore how clan control was enacted in a large ITproject at a major logistics organization in which clan control was quickly instituted to avoid an impending project failure. Our research contributes to theory in three ways: (1) we reconcile the two differing views of clan control into a single framework, (2) we explain the role of controllers in enacting clan control, and (3) we clarify how formal control can be employed to develop clan control.

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  • Mental Schemas of Robots as More Human-Like Are Associated with Higher Blood Pressure and Negative Emotions in a Human-Robot Interaction

    Broadbent, Elizabeth; Lee, Y; Stafford, R; Kuo, I-Han; MacDonald, Bruce (2011)

    Journal article
    The University of Auckland Library

    Robots are often portrayed in the media as humanlike, yet research suggests that people prefer to interact with robots that are not human-like. This study aimed to investigate whether people???s mental schemas about robots??? humanness were associated with their reactions to a robot. It was hypothesised that people who thought of robots as more human-like would be more anxious when subsequently interacting with a robot. Fifty-seven participants aged over 40 years were asked to draw their idea of a healthcare robot using standardised instructions before seeing the real robot. They reported their emotions at baseline and a medical student measured their blood pressure. The drawings were categorised as human-like or box-like by the researchers and drawing size was measured. Participants were then introduced to a robot that measured their blood pressure, and they reported their emotions during the interaction. Participants who had drawn a human-like robot had signi???cantly greater increases in blood pressure readings and negative emotions from baseline in reaction to the robot compared to those who had drawn a box-like robot. Larger drawings of healthcare robots predicted higher ratings of negative emotions during the robot interaction. This study suggests that people who have mental schemas that robots are human-like experience heightened wariness in interactions with robots. Larger drawings of robots may indicate greater anxiety towards them. Assessing mental schemas of robot human-likeness is an important consideration for the acceptance of social robots. Standardised drawing instructions and scoring are a useful method to assess cognitions and emotions towards robots.

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  • Attitudes and Reactions to a Healthcare Robot

    Broadbent, Elizabeth; Kuo, I-Han; Lee, YI; Rabindran, J; Kerse, Ngaire; Stafford, R; MacDonald, Bruce (2010-06)

    Journal article
    The University of Auckland Library

    Objective: The use of robots in healthcare is a new concept. The public's perception and acceptance is not well understood. The objective was to investigate the perceptions and emotions toward the utilization of healthcare robots among individuals over 40 years of age, investigate factors contributing to acceptance, and evaluate differences in blood pressure checks taken by a robot and a medical student. Materials and Methods: Fifty-seven (n???=???57) adults aged over 40 years and recruited from local general practitioner or gerontology group lists participated in two cross-sectional studies. The first was an open-ended questionnaire assessing perceptions of robots. In the second study, participants had their blood pressure taken by a medical student and by a robot. Patient comfort with each encounter, perceived accuracy of each measurement, and the quality of the patient interaction were studied in each case. Readings were compared by independent t-tests and regression analyses were conducted to predict quality ratings. Results: Participants' perceptions about robots were influenced by their prior exposure to robots in literature or entertainment media. Participants saw many benefits and applications for healthcare robots, including simple medical procedures and physical assistance, but had some concerns about reliability, safety, and the loss of personal care. Blood pressure readings did not differ between the medical student and robot, but participants felt more comfortable with the medical student and saw the robot as less accurate. Although age and sex were not significant predictors, individuals who held more positive initial attitudes and emotions toward robots rated the robot interaction more favorably. Conclusions: Many people see robots as having benefits and applications in healthcare but some have concerns. Individual attitudes and emotions regarding robots in general are likely to influence future acceptance of their introduction into healthcare processes.

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  • The relationship between high-performance work practices and employee attitudes: An investigation of additive and interaction effects

    Macky, K; Boxall, Peter (2007)

    Journal article
    The University of Auckland Library

    In order to improve our understanding of mediating variables inside the ???black box??? of the ???rm???s labour management, this paper examines the relationship between high-performance work system (HPWS) practices and employee attitudes. Using a randomly selected, national population sample, clear evidence was found for a positive relationship between HPWS practices and the attitudinal variables of job satisfaction, trust in management, and organizational commitment, implying that HPWS can provide winwin outcomes for employees and employers. However, the study also tests ??? from an employee perspective ??? the ???complementarities thesis??? and ???nds negative interaction effects among HPWS practices. This strengthens the argument that there are likely to be limits to the positive outcomes of HPWSs for employees. Evidence of sequencing in the employee attitudinal responses to HPWSs was also found, with job satisfaction as the key mediating variable.

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  • Explaining bank distress in Eastern European transition economies

    Mannasoo, K; Mayes, David (2009-02)

    Journal article
    The University of Auckland Library

    This paper considers the joint role of macroeconomic, structural and bank-specific factors in explaining the occurrence of banking problems in the nineteen Eastern European transition countries over the last decade. With data at the individual bank level we show, using a discrete time survival model, that all three factors interact in their impact and have a rich dynamic profile, which underlines the highly volatile cycles challenging the stability of banks in this region. A fragile funding basis accompanied by high exposure to market risk in an environment of reforms and macroeconomic disturbances is the typical precursor of bank distress.

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  • Changing trends in operative delivery performed at full dilatation over a 10-year period.

    Loudon, JA; Groom, Katie; Hinkson, L; Harrington, D; Paterson-Brown, S (2010-05)

    Journal article
    The University of Auckland Library

    This study was a systematic anonymous audit of routinely collected data in a tertiary referral obstetric unit in London and included data from deliveries over a 10-year period (1992-2001). Data for all caesarean sections at full dilatation were collected, including maternal demographic information, the grade of operating clinician, and the place of delivery. Neonatal data collected included birth weight and umbilical arterial pH. No changes in the demographics of the population were observed. No increased rates of malposition were observed. Birth weight did not change. Increasing preference for the ventouse over forceps (ratio 0.2:1 to 1.9:1) over the decade (p = 0.002) was seen with an increased tendency to conduct the delivery in the operating theatre (p = 0.0025). Rate of caesarean section at full dilatation increased (2% by 2001). Increasing failures of operative vaginal delivery, especially using the ventouse (regression coefficient p = 0.025), and reduced attempts at instrumentation (regression coefficient p = 0.002) were seen.

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  • The impact of fetal fibronectin testing for women with symptoms of preterm labour in routine clinical practice within a New Zealand population.

    Groom, Katie; Liu, E; Allenby, Keith (2006)

    Journal article
    The University of Auckland Library

    Aims:??? To perform a comparative analysis of antenatal management received according to the results of cervico-vaginal fetal fibronectin (fFN) testing, and to review preterm delivery rates and fFN predictive values within a New Zealand population of women presenting with threatened preterm labour. Methods:??? Case note review of all fFN tests performed at Middlemore Hospital, South Auckland from August 2003 to March 2005 (n = 199). Data collected included risk factors for preterm delivery, signs and symptoms at presentation, antenatal management received after fFN test and outcome and delivery details. Positive and negative fFN results were compared. Results:??? Women with a positive fFN were more likely to receive antenatal corticosteroids (96.4 vs 4.7% RR 8.74 (95% CI 5.40???14.17)) and tocolysis (71.4 vs 2.4% RR 8.10 (95% CI 4.49???14.59)) and to be admitted antenatally (96.4 vs 54.4% RR 1.77 (95% CI 1.50???2.10)) with a higher mean cost of treatment ($NZ967.47 vs $NZ335.27 P < 0.05). Rates of delivery < 34 weeks were higher in those with a positive fFN (41.9 vs 0.7% RR 62.06 (95% CI 8.43???457.14)). Conclusion:??? Women with a positive fFN result received different treatment to those with a negative fFN. Use of fFN test in routine clinical practice allows management and resources to be targeted more appropriately and may limit unnecessary interventions.

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  • Improved bleeding profile and tolerability of tibolone versus transdermal E2/NETA treatment in postmenopausal women with female sexual dysfunction.

    Nijland, EA; Nathorst-B????s, J; Palacios, S; van de Weijer, Petrus; Davis, S; Stathopoulos, VM; Birkhaeuser, MH; von Mauw, E; Mulder, RJ; Schultz, WC; LISA study investigators group (2009-04)

    Journal article
    The University of Auckland Library

    Objectives To compare the incidence of vaginal spotting/bleeding events and breast pain between therapy with tibolone 2.5 mg and continuous combined transdermal estradiol (E2)/norethisterone acetate (NETA) 50 ??g/140 ??g after 24 weeks of treatment. Methods A double-blind, double-dummy, randomized, controlled trial was performed and assessments were performed at baseline, week 12 and week 24. Bleeding/spotting events were recorded in a daily diary. Breast signs and symptoms were collected as adverse events. Results A total of 403 women (mean age 56 years) were randomized. Bleeding/spotting events during weeks 1???12 with tibolone and E2/NETA were experienced by 16% and 56% of women, respectively (p < 0.001). The corresponding percentages during weeks 13???24 were 12% and 51%, respectively (p < 0.001). E2/NETA was significantly more likely than tibolone to be associated with vaginal hemorrhage (11% vs. 0%; p < 0.001) and breast signs and symptoms (11% vs. 4%; p = 0.015). Early discontinuations resulting from adverse events were significantly more common in the E2/NETA group than in the tibolone group (20% vs. 12%), primarily related to withdrawal due to vaginal hemorrhage (8% vs. 0%). Conclusions Tibolone has a significantly better tolerability profile than transdermal E2/NETA as measured by vaginal bleeding, breast pain and treatment continuation.

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  • Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability.

    Hammar, ML; van de Weijer, Petrus; Franke, HR; Pornel, B; von Mauw, EM; Nijland, EA; TOTAL Study Investigators Group (2007-12)

    Journal article
    The University of Auckland Library

    Objectives The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/ NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy. Design A randomised, double-blind, double-dummy, group comparative intervention trial. Setting Multicentre study executed in 32 centres in 7 European countries. Sample Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45???65 years. Methods Participants were randomised to receive 2.5 mg tibolone or 1 mg 17b estradiol plus 0.5 mg norethisterone acetate (E2/ NETA) daily for 48 weeks. Main outcome measures Prevalence of vaginal bleeding, hot flushes and adverse events. Results The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7???9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001). Conclusion Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.

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  • Complementary and hormonal therapy for vasomotor symptom relief: a conservative clinical approach.

    Nachtigall, LE; Baber, RJ; Barentsen, R; Durand, N; Panay, N; Pitkin, J; van de Weijer, Petrus; Wysocki, S (2006-04)

    Journal article
    The University of Auckland Library

    Vasomotor symptoms are the most common menopausal symptom experienced by women and the leading reason menopausal women seek health care advice. The recent shift towards a more conservative use of hormone therapy (HT) during menopause has prompted the need for treatment regimens to be individualized according to symptom severity. Our objective was to develop a new algorithm that enables practitioners to customize treatment regimens according to symptom severity. In order to develop a comprehensive treatment algorithm, we conducted a literature review and considered the findings from recently published treatment guidelines from around the world. We also evaluated the results of systematic reviews investigating the efficacy and safety of complementary and alternative medicines. We found a growing trend away from prescription HT in women with mild to moderate symptoms and an increasing trend toward lifestyle modification and the use of complementary and alternative medicines. On the basis of these findings, we have developed an algorithm that accounts for symptom severity. The algorithm presented here provides treatment options based on symptom severity and a comprehensive approach for integrating lifestyle modifications and complementary therapies with prescription treatment regimens.

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  • Heart Rate Variability and Ventilatory Efficiency

    Brown, SJ; Brown, Julie (2009-07)

    Journal article
    The University of Auckland Library

    The aims of this investigation were to identify possible associations between the resting high frequency component of heart rate variability and measures of ventilatory efficiency, determined during exercise, in a group of endurance trained athletes. V'E, V'CO2, and V'O2 were measured during incremental exercise up to the anaerobic threshold (AT) and up to volitional exhaustion (V'O2 max) in 12 subjects. Resting high frequency heart rate variability (HFNU), determined using spectral analysis of ECG traces, was correlated with the V'E vs. V'CO2 slope calculated from data up to the AT, where a negative linear relation between the V'E vs. V'CO2 slope and HFNU was recorded (R2=0.69). Also, resting HFNU was correlated with the V'E vs. V'CO2 slope, when the data used for slope calculation included all V'E vs. V'CO2 data up to V'O2 max (R2=0.56). However, there was no evidence of association between the minimum V'E:V'CO2 and resting HFNU (R2=0.08). Negative relations between V'E vs. V'CO2 slope and resting HFNU suggest that HFNU plays a role in matching blood flow in the lung to alveolar ventilation throughout the ventilatory cycle.

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  • Age-associated changes in VO2 and power output - A cross-sectional study of endurance trained New Zealand cyclists

    Brown, SJ; Ryan, HJ; Brown, Julie (2007-12)

    Journal article
    The University of Auckland Library

    Age-associated changes in power and maximal oxygen consumption (VO2max) were studied in a cross section of endurance trained cyclists. Subjects (n = 56) performed incremental cycling exercise, during which capillary blood lactate [La-] was measured. Power output increased by 30 Watts during each 5 minutes stage, with initial power output based on individual ability. When [La-] was >4.5 mmol??L-1, subjects were given a 10 min recovery at a power output approximately 50% below estimated power at [La-]4mmol. Subjects then performed an incremental test (1 minute stages) to VO2max. Decline in VO2max was 0.65 ml??kg-1??min-1??year-1 (r = -0.72, p < 0.01) for males, and 0.39 ml??kg-1??min-1??year-1 (r = -0.54, p < 0.05) for females. Power at VO2max decreased by 0.048 W kg-1??year-1 (r = -0.72, p < 0.01) in males. Power at [La-]4mmol decreased by 0.044 W kg-1??year-1 (r = -0.76, p < 0.01) in males, and by 0.019 W kg-1??year-1 (r = -0.53, p < 0.05) in females. Heart rate at VO2max (HRmax) showed a weaker correlation with age in males (r = -0.36, p < 0.05). The age-associated changes in maximum aerobic power and sub-maximal power were gender- specific, thus suggesting different age-related effects on the systems which support exercise in males and females.

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  • Cardiac vagal control and respiratory sinus arrhythmia during hypercapnia in humans

    Brown, SJ; Mundel, T; Brown, Julie (2007-12)

    Journal article
    The University of Auckland Library

    Normoxic hypercapnia may increase high-frequency (HF) power in heart rate variability (HRV) and also increase respiratory sinus arrhythmia (RSA). Low-frequency (LF) power may remain unchanged. In this study, 5-min ECG recordings (N = 10) were analyzed in time and frequency domains while human subjects breathed normoxic 5% CO2 (5%CO2) or room air (RA). Tidal volume (VT), inhalatory (TI), and exhalatory (TE) times of breaths in the final minute were measured. ECG time domain measures were unaffected by CO2 inhalation (P > 0.05). Following natural logarithmic transformation (LN), LFLN was unaltered (RA: 7.14 ?? 0.95 vs. 5%CO2: 7.35 ?? 1.12, P > 0.05), and HFLN increased (RA: 7.65 ?? 1.37 vs. 5%CO2: 8.58 ?? 1.11, P < 0.05) with CO2 inhalation. When changes in total power (NU) were corrected, LFNU decreased (RA: 34.4 ?? 22.9 vs. 5%CO2: 23.8 ?? 23.1, P < 0.01), and HFNU increased (RA: 56.5 ?? 22.3 vs. 5%CO2: 66.8 ?? 22.9, P < 0.01) with CO2 inhalation. TI (RA: 2.0 ?? 1.0 vs. 5%CO2: 1.9 ?? 0.8 s) and TE (RA: 2.5 ?? 1.1 vs. 5%CO2: 2.4 ?? 0.9 s) remained unchanged, but VT increased with CO2 inhalation (RA: 1.1 ?? 0.3 vs. 5%CO2: 2.0 ?? 0.8 L, P < 0.001). Heart rates during inhalation (RA: 35.2 ?? 4.4, 5%CO2: 34.5 ?? 4.8 beats min???1) were different from heart rates during exhalation (RA: 28.8 ?? 4.4, 5%CO2: 29.1 ?? 3.1 beats min???1). Hypercapnia did not increase the clustering of heart beats during inhalation, and we suggest that the HF component may not adequately reflect RSA.

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  • Age-related decline in mitochondrial DNA copy number in isolated human pancreatic islets.

    Cree, Lynsey; Patel, SK; Pyle, A; Lynn, S; Turnbull, DM; Chinnery, PF; Walker, M (2008-08)

    Journal article
    The University of Auckland Library

    Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta cells, which might in turn contribute to the age-related decline in insulin secretory capacity.

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  • Normal levels of wild-type mitochondrial DNA maintain cytochrome c oxidase activity for two pathogenic mitochondrial DNA mutations but not for m.3243A-->G.

    Durham, SE; Samuels, DC; Cree, Lynsey; Chinnery, PF (2007-07)

    Journal article
    The University of Auckland Library

    Mitochondrial DNA (mtDNA) mutations are a common cause of human disease and accumulate as part of normal ageing and in common neurodegenerative disorders. Cells express a biochemical defect only when the proportion of mutated mtDNA exceeds a critical threshold, but it is not clear whether the actual cause of this defect is a loss of wild-type mtDNA, an excess of mutated mtDNA, or a combination of the two. Here, we show that segments of human skeletal muscle fibers harboring two pathogenic mtDNA mutations retain normal cytochrome c oxidase (COX) activity by maintaining a minimum amount of wild-type mtDNA. For these mutations, direct measurements of mutated and wild-type mtDNA molecules within the same skeletal muscle fiber are consistent with the "maintenance of wild type" hypothesis, which predicts that there is nonselective proliferation of mutated and wild-type mtDNA in response to the molecular defect. However, for the m.3243A-->G mutation, a superabundance of wild-type mtDNA was found in many muscle-fiber sections with negligible COX activity, indicating that the pathogenic mechanism for this particular mutation involves interference with the function of the wild-type mtDNA or wild-type gene products.

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  • Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease.

    Craven, L; Tuppen, HA; Greggains, GD; Harbottle, SJ; Murphy, JL; Cree, Lynsey; Murdoch, AP; Chinnery, PF; Taylor, RW; Lightowlers, RN; Herbert, M; Turnbull, DM (2010-05-06)

    Journal article
    The University of Auckland Library

    Mutations in mitochondrial DNA (mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births and at least 1 in 10,000 adults in the UK are affected by mtDNA disease. Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease. Here we show that transfer of pronuclei between abnormally fertilized human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure we found the average level of carry-over after transfer of two pronuclei is less than 2.0%, with many of the embryos containing no detectable donor mtDNA. We believe that pronuclear transfer between zygotes, as well as the recently described metaphase II spindle transfer, has the potential to prevent the transmission of mtDNA disease in humans.

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