92,971 results

  • The chaperone proteins HSP70, HSP40/DnaJ and GRP78/BiP supress misfolding and formation of beta-sheet-containing aggregates by human amylin: apotential role for defective chaperone biology in Type 2 diabetes.

    Brittain, Tom; Chien, V; Aitken, Jacqueline; Zhang, S; Buchanan, Christina; Hickey, Anthony; Cooper, Garth; Loomes, Kerry (2010)

    Journal article
    The University of Auckland Library

    Misfolding of the islet ??-cell peptide hA (human amylin) into ??-sheet-containing oligomers is linked to ??-cell apoptosis and the pathogenesis of T2DM (Type 2 diabetes mellitus). In the present study, we have investigated the possible effects on hA misfolding of the chaperones HSP (heat-shock protein) 70, GRP78/BiP (glucose-regulated protein of 78 kDa/immunoglobulin heavy-chain-binding protein) and HSP40/DnaJ. We demonstrate that hA underwent spontaneous time-dependent ??-sheet formation and aggregation by thioflavin-T fluorescence in solution, whereas rA (rat amylin) did not. HSP70, GRP78/BiP and HSP40/DnaJ each independently suppressed hA misfolding. Maximal molar protein/hA ratios at which chaperone activity was detected were 1:200 (HSP70, HSP40/DnaJ and GRP78/BiP). By contrast, none of the chaperones modified the secondary structure of rA. hA, but not rA, was co-precipitated independently with HSP70 and GRP78/BiP by anti-amylin antibodies. As these effects occur at molar ratios consistent with chaperone binding to relatively rare misfolded hA species, we conclude that HSP70 and GRP78/BiP can detect and bind misfolded hA oligomers, thereby effectively protecting hA against bulk misfolding and irreversible aggregation. Defective ??-cell chaperone biology could contribute to hA misfolding and initiation of apoptosis in T2DM.

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  • 3D structure of the Yersinia entomophaga toxin complex and implications for insecticidal activity

    Landsberg, MJ; Jones, SA; Rothnagel, R; Busby, Jason; Marshall, SDG; Simpson, RM; Lott, Jeremy; Hankamer, B; Hurst, MRH (2011)

    Journal article
    The University of Auckland Library

    Toxin complex (Tc) proteins are a class of bacterial protein toxins that form large, multisubunit complexes. Comprising TcA, B, and C components, they are of great interest because many exhibit potent insecticidal activity. Here we report the structure of a novel Tc, Yen-Tc, isolated from the bacterium Yersinia entomophaga MH96, which differs from the majority of bacterially derived Tcs in that it exhibits oral activity toward a broad range of insect pests, including the diamondback moth (Plutella xylostella). We have determined the structure of the Yen-Tc using single particle electron microscopy and studied its mechanism of toxicity by comparative analyses of two variants of the complex exhibiting different toxicity profiles. We show that the A subunits form the basis of a fivefold symmetric assembly that differs substantially in structure and subunit arrangement from its most well characterized homologue, the Xenorhabdus nematophila toxin XptA1. Histopathological and quantitative dose response analyses identify the B and C subunits, which map to a single, surface-accessible region of the structure, as the sole determinants of toxicity. Finally, we show that the assembled Yen-Tc has endochitinase activity and attribute this to putative chitinase subunits that decorate the surface of the TcA scaffold, an observation that may explain the oral toxicity associated with the complex.

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  • Connections between survey calibration estimators and semiparametric models for incomplete data

    Lumley, Thomas; Shaw, PA; Dai, JY (2011)

    Journal article
    The University of Auckland Library

    Survey calibration (or generalized raking) estimators are a standard approach to the use of auxiliary information in survey sampling, improving on the simple Horvitz???Thompson estimator. In this paper we relate the survey calibration estimators to the semiparametric incomplete-data estimators of Robins and coworkers, and to adjustment for baseline variables in a randomized trial. The development based on calibration estimators explains the ???estimated weights??? paradox and provides useful heuristics for constructing practical estimators. We present some examples of using calibration to gain precision without making additional modelling assumptions in a variety of regression models.

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  • Fault growth at a nascent slow-spreading ridge: 2005 Dabbahu rifting episode, Afar

    Rowland, Julie; Baker, E; Ebinger, C; Keir, D; Kidane, T; Biggs, J; Hayward, N; Wright, TJ (2007)

    Journal article
    The University of Auckland Library

    We present a preliminary account of the near-field surface strain associated with a major magmatic rifting episode at a nascent slow spreading ridge in the Afar depression. Between 2005 September 14 and October 4, a volcanic eruption and 163 earthquakes (mb > 3.9), including seismic tremor, occurred within the ???60-km-long Dabbahu magmatic segment. Results of the early response team demonstrated that ground deformation, derived from satellite radar data (InSAR), together with seismicity, is consistent with dyke-induced deformation along the entire length of the segment.We document the distribution of brittle strain associated with the early part of this rifting cycle to verify the predicted pattern of deformation and constrain a conceptual model for normal fault growth in Afar, with general application to other slow spreading divergent margins. Our field investigations concentrate on the northern half of the segment, which ruptured through to the surface over a length of >30 km and a width of ???5 km, consistent with the pattern of microseismicity recorded using a network deployed ???1 month after the initial onset of the rifting episode on September 14. Severe ground shaking during the event was more widespread; fresh rock fall is common across the entire magmatic segment, particularly at the intersections between faults. Recent ground breaks, in the form of reactivated or newly initiated normal faults and fissures, opened with horizontal displacements up to 3 m and vertical displacements locally up to 5 m, but commonly ???2 m. These structures are generally subvertical and open along pre-existing cooling joints. Fault offset is greater than expected given the magnitude of earthquakes during the episode. The axial relief that developed consequent on fault and fissure initiation and reactivation during the 2005 Dabbahu episode is consistent with that of the entire magmatic segment.We therefore suggest that melt delivery is sufficiently frequent that favourable stress conditions for faulting are primarily achieved during dyke events.

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  • Design and analysis of two-phase experiments for gene expression microarray experiments

    Jarrett, RG; Ruggiero, Katya (2008)

    Journal article
    The University of Auckland Library

    Gene expression microarrayexp eriments are intrinsicallyt wo-phase experiments. Messenger RNA (mRNA), required for the microarrayexp eriment, must first be derived from plants or animals that are exposed to a set of treatments in a previous experiment (Phase 1). The mRNA is then used in the subsequent laboratory-based microarray experiment (Phase 2) from which gene expression is measured and ultimatelyanaly zed. We show that obtaining a valid test for the effects of treatments on gene expression depends on the design of both the Phase 1 and Phase 2 experiments. Examples show that the multiple dyeswap design at Phase 2 is more robust than the alternating loop design in the absence of prior knowledge of the relative size of variation in the Phase 1 and Phase 2 experiments.

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  • Pathway Activity Profiling (PAPi): from the metabolite profile to the metabolic pathway activity

    Aggio, Raphael; Ruggiero, Katya; Villas-Boas, Silas (2010-12)

    Journal article
    The University of Auckland Library

    Motivation: Metabolomics is one of the most recent omicstechnologies and uses robust analytical techniques to screen low molecular mass metabolites in biological samples. It has evolved very quickly during the last decade. However, metabolomics datasets are considered highly complex when used to relate metabolite levels to metabolic pathway activity. Despite recent developments in bioinformatics, which have improved the quality of metabolomics data, there is still no straightforward method capable of correlating metabolite level to the activity of different metabolic pathways operating within the cells. Thus, this kind of analysis still depends on extremely laborious and time-consuming processes. Results: Here, we present a new algorithm Pathway Activity Profiling (PAPi) with which we are able to compare metabolic pathway activities from metabolite profiles. The applicability and potential of PAPi was demonstrated using a previously published data from the yeast Saccharomyces cerevisiae. PAPi was able to support the biological interpretations of the previously published observations and, in addition, generated new hypotheses in a straightforward manner. However, PAPi is time consuming to perform manually. Thus, we also present here a new R-software package (PAPi) which implements the PAPi algorithm and facilitates its usage to quickly compare metabolic pathways activities between different experimental conditions. Using the identified metabolites and their respective abundances as input, the PAPi package calculates pathways??? Activity Scores, which represents the potential metabolic pathways activities and allows their comparison between conditions. PAPi also performs principal components analysis and analysis of variance or t-test to investigate differences in activity level between experimental conditions. In addition, PAPi generates comparative graphs highlighting up- and down-regulated pathway activity. Availability: These datasets are available in http://www.4shared. com/file/hTWyndYU/extra.html and http://www.4shared.com/file/ VbQIIDeu/intra.html. PAPi package is available in: http://www. 4shared.com/file/s0uIYWIg/PAPi_10.html Contact: s.villas-boas@auckland.ac.nz Supplementary information: Supplementary data are available at Bioinformatics online.

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  • Determining the subjective effects of TFMPP in human males

    Jan, Reem; Lin, Joanne; Lee, Hee; Sheridan, Jane; Kydd, Robert; Kirk, Ian; Russell, Bruce (2010)

    Journal article
    The University of Auckland Library

    Rationale Trifluoromethylphenyl piperazine (TFMPP) is an active constituent of a relatively new group of recreational drugs known as ???party pills???. TFMPP has been anecdotally reported to induce mild psychedelic effects similar to lysergic acid diethylamide and psilocybin. There has been no research about the subjective effects of TFMPP in humans. Objectives This study aimed to investigate the subjective effects of TFMPP in human males. Methods A randomised, double-blind, placebo-controlled trial design was used to investigate the subjective effects of TFMPP in 30 healthy, non-smoking male volunteers (mean age 24??4 years). Participants were randomised into two groups and given either TFMPP 60 mg (n=15) or placebo (n=15). Each participant completed three rating scales, the Addiction Research Centre Inventory (ARCI), the Profile of Mood States (POMS) and the Visual Analogue Scales (VAS), both before and 120 min after drug administration. Results Results from the ARCI indicated that TFMPP produced increases in ???dysphoria??? and ???dexamphetaminelike effects???. TFMPP also increased ratings of ???tension/ anxiety??? and ???confusion/bewilderment??? as rated on the POMS. Results from the VAS indicated increases in ???drug liking???, ???high??? and ???stimulated??? ratings relevant to placebo. Conclusions Increased ratings of ???dexamphetamine-like effects???, ???tension/anxiety???, ???stimulated??? and ???high??? following TFMPP administration resemble the subjective effects of common amphetamine-type stimulants. However, increases in ???dysphoria??? and ???confusion/bewilderment??? ratings following TFMPP are more commonly associated with drugs that have greater effects on serotonin release, binding and reuptake such as 1-[3-chlorophenyl]-piperazine, fenfluramine and lysergic acid diethylamide.

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  • Explicit and Implicit Catalysts of Consumer Resistance: The Effects of Animosity, Cultural Salience and Country of Origin on Subsequent Choice

    Russell, D; Russell, Cristel (2006)

    Journal article
    The University of Auckland Library

    This paper identifies conditions that activate animosity feelings and in turn affect global consumers' choices. Three experiments conducted in two countries test the effects of a movie's country-of-origin and consumers' levels of animosity on subsequent movie choices. Two catalysts of animosity are explored: an explicit scenario and an implicit cultural salience prompt. Cultural resistance emerges in the form of increased preference for domestic movies when animosity is activated and consumers are exposed to related country-of-origin information about a first movie. A similar pattern of cultural resistance appears when, instead of consciously activating animosity, cultural identity is made salient.

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  • Modelling wave propagation in two-dimensional structures using finite element analysis

    Mace, Brian; Manconi, E (2008)

    Journal article
    The University of Auckland Library

    A method is described by which the dispersion relations for a two-dimensional structural component can be predicted from a finite element (FE) model. The structure is homogeneous in two dimensions but the properties might vary through the thickness. This wave/finite element (WFE) method involves post-processing the mass and stiffness matrices, found using conventional FE methods, of a segment of the structure. This is typically a 4-noded, rectangular segment, although other elements can be used. Periodicity conditions are applied to relate the nodal degrees of freedom and forces. The wavenumbers???real, imaginary or complex???and the frequencies then follow from various resulting eigenproblems. The form of the eigenproblem depends on the nature of the solution sought and may be a linear, quadratic, polynomial or transcendental eigenproblem. Numerical issues are discussed. Examples of a thin plate, an asymmetric laminated plate and a laminated foam-cored sandwich panel are presented. For the last two examples, developing an analytical model is a formidable task at best. The method is seen to give accurate predictions at very little computational cost. Furthermore, since the element matrices are typically found using a commercial FE package, the meshing capabilities and the wealth of existing element libraries can be exploited.

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  • Finite element analysis of the vibrations of waveguides and periodic structures

    Duhamel, D; Mace, Brian; Brennan, MJ (2006)

    Journal article
    The University of Auckland Library

    Many structural components can be regarded as waveguides. They are uniform in one direction so that the cross section of the waveguide has the same physical and geometric properties at all points along the axis of the waveguide. In this paper a method is presented to calculate the forced response of such a structure using a combination of wave and finite element (FE) approaches. The method involves post-processing a conventional, but low order, FE model in which the mass and stiffness matrices are typically found using a conventional FE package. A section of the waveguide is meshed and the eigenvalues and eigenvectors of the resulting transfer matrix found. The eigenvectors form a set of basis functions for the analysis of the structure as a whole, allowing the global dynamic stiffness matrix to be built easily and then the forced response to be calculated very efficiently. The main advantage of the approach over the alternative waveguide/FE approach often termed the spectral FE method, is that conventional FE packages can be used to form the stiffness and mass matrices so that structures with complex geometries or material distributions can be analysed with relative ease. To demonstrate the efficacy of the method examples of the forced response for a finite beam and plate-strip are presented.

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  • What does care mean? Perceptions of people approaching the end of life

    Janssen, AL; MacLeod, Roderick (2010)

    Journal article
    The University of Auckland Library

    Objective: This project sought to better understand the nature of medical care from the perspective of people approaching the end of life. Method:We asked 13 people who were dying (and a family member for each) to describe their care and the ways in which doctors??? behavior fosters or inhibits the feeling that they were cared for as individuals. Interviews took a phenomenological approach. Data analysis was thematic. Results: Examples used by participants as evidence of care varied widely and showed the potentially complex nature of quality care. Participants??? descriptions reflect the many ways people can impart and experience care as unique individuals in the medical context. They also provide clear examples of what uncaring behaviour looks and feels like. Significance of results: The importance of care was clearly illustrated through descriptions of the benefits of caring behavior and the negative consequences of uncaring behavior. In order to demonstrate the empathy and compassion expected and assumed of medical graduates and engender a feeling of being cared for among their patients, doctors need to invite and develop a relationship with those they are caring for. There needs to be a focus on each member of the caring relationship primarily as individual human beings.

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  • Body composition, physical fitness, functional performance, quality of life, and fatigue benefits of exercise for prostate cancer patients: a systematic review.

    Keogh, JW; MacLeod, Roderick (2012-01)

    Journal article
    The University of Auckland Library

    Prostate cancer patients, especially those on androgen deprivation therapy (ADT), experience many symptoms that make it difficult to maintain their independence and quality of life. Because ADT acts by means of reducing testosterone production, exercise may offset many of the ADT side effects and those of the cancer itself.

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  • Design and validation of a comprehensive faecal incontinence questionnaire

    Macmillan, Alexandra; Merrie, Arend; Marshall, Roger; Parry, Bryan (2008)

    Journal article
    The University of Auckland Library

    PURPOSE: Fecal incontinence can have a profound effect on quality of life. Its prevalence remains uncertain because of stigma, lack of consistent definition, and dearth of validated measures. This study was designed to develop a valid clinical and epidemiologic questionnaire, building on current literature and expertise. METHODS: Patients and experts undertook face validity testing. Construct validity, criterion validity, and test-retest reliability was undertaken. Construct validity comprised factor analysis and internal consistency of the quality of life scale. The validity of known groups was tested against 77 control subjects by using regression models. Questionnaire results were compared with a stool diary for criterion validity. Test-retest reliability was calculated from repeated questionnaire completion. RESULTS: The questionnaire achieved good face validity. It was completed by 104 patients. The quality of life scale had four underlying traits (factor analysis) and high internal consistency (overall Cronbach alpha=0.97). Patients and control subjects answered the questionnaire significantly differently (P<0.01) in known-groups validity testing. Criterion validity assessment found mean differences close to zero. Median reliability for the whole questionnaire was 0.79 (range, 0.35???1). CONCLUSIONS: This questionnaire compares favorably with other available instruments, although the interpretation of stool consistency requires further research. Its sensitivity to treatment still needs to be investigated.

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  • A screening method for prioritizing non-target invertebrates for improved biosafety testing of transgenic crops

    Todd, JH; Ramankutty, P; Barraclough, EI; Malone, Louise (2008)

    Journal article
    The University of Auckland Library

    We have developed a screening method that can be used during the problem formulation phase of risk assessment to identify and prioritize non-target invertebrates for risk analysis with any transgenic plant. In previously published protocols for this task, five criteria predominated. These criteria have been combined by our method in a simple model which assesses: (1) the possible level of risk presented by the plant to each invertebrate species (through measurements of potential hazard and exposure, the two principal criteria); (2) the hypothetical environmental impact of this risk (determined by the currently known status of the species' population in the ecosystem and its potential resilience to environmental perturbations); (3) the estimated economic, social and cultural value of each species; and (4) the assessed ability to conduct tests with the species. The screening method uses information on each of these criteria entered into a specially designed database that was developed using Microsoft Access 2003. The database holds biological and ecological information for each non-target species, as well as information about the transgenic plant that is the subject of the risk assessment procedure. Each piece of information is then ranked on the basis of the value of the information to each criterion being measured. This ranking system is flexible, allowing the method to be easily adapted for use in any agro-ecosystem and with any plant modification. A model is then used to produce a Priority Ranking of Non-Target Invertebrates (PRONTI) score for each species, which in turn allows the species to be prioritized for risk assessment. As an example, the method was used to prioritize non-target invertebrates for risk assessment of a hypothetical introduction of Bacillus thuringiensis (Bt) Cry1Ac-expressing Pinus radiata trees into New Zealand.

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  • Is genetic information relevantly different from other kinds of non-genetic information in the life insurance context?

    Malpas, Phillipa (2008)

    Journal article
    The University of Auckland Library

    Within the medical, legal and bioethical literature, there has been an increasing concern that the information derived from genetic tests may be used to unfairly discriminate against individuals seeking various kinds of insurance; particularly health and life insurance. Consumer groups, the general public and those with genetic conditions have also expressed these concerns, specifically in the context of life insurance. While it is true that all insurance companies may have an interest in the information obtained from genetic tests, life insurers potentially have a very strong incentive to (want to) use genetic information to rate applicants, as individuals generally purchase their own cover and may want to take out very large policies. This paper critically focuses on genetic information in the context of life insurance. We consider whether genetic information differs in any relevant way from other kinds of non-genetic information required by and disclosed to life insurance companies by potential clients. We will argue that genetic information should not be treated any differently from other types of health information already collected from those wishing to purchase life insurance cover.

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  • Predictive genetic testing of children for adult-onset diseases and psychological harm

    Malpas, Phillipa (2008)

    Journal article
    The University of Auckland Library

    One of the central arguments given to resist testing currently healthy, asymptomatic children for adult-onset diseases is that they may be psychologically harmed by the knowledge gained from such tests. In this discussion I examine two of the most serious arguments: children who are tested may face limited futures, and that testing may result in damage to the child's self esteem (where the test result returns a positive diagnosis). I claim that these arguments do not stand up to critical evaluation. In conclusion, whilst I do not suggest that all at-risk children should be tested for adult-onset diseases we ought to listen carefully to some parental requests for such testing because the putative psychological harms may not be as significant or likely as initially thought. This is because parents generally have the best interests of their children at heart and if they are properly supported and educated about predictive genetic testing and the possible consequences, then the risk of psychological harms occurring may be ameliorated.

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  • Efficiency and productivity growth in the banking industry of Central and Eastern Europe

    Koutsomanoli-Filippaki, A; Margaritis, Dimitrios; Staikouras, C (2009)

    Journal article
    The University of Auckland Library

    We employ the directional technology distance function and provide estimates of bank efficiency and productivity change across Central and Eastern European (CEE) countries and across banks with different ownership status for the period 1998???2003. Our results demonstrate the strong links of competition and concentration with bank efficiency. They also show that productivity for the whole region initially declined but has improved more recently with further progress on institutional and structural reforms. Input-biased technical change has been consistently positive throughout the entire period suggesting that the reforms have induced favorable changes in relative input prices and input mix. However we find evidence of diverging trends in productivity growth patterns across banking industries and that foreign banks outperform domestic private and state-owned banks both in terms of efficiency and productivity gains. Overall, we find that productivity change in CEE is driven by technological change rather than efficiency change.

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  • Does young adult suicide cluster geographically in Scotland?

    Exeter, Daniel; Boyle, PJ (2007)

    Journal article
    The University of Auckland Library

    Background: Suicide rose dramatically among young adults in Scotland between 1980-1982 and 1999-2001, especially among those living in deprived areas. Objective: To determine whether there are statistically significant geographical clusters of suicide and undetermined deaths among those aged 15 to 44 years in Scotland, and whether these persist through time. Methods: Deaths from suicide and undetermined causes by young adults in Scotland for three periods-1980 to 1982, 1990 to 1992, and 1999 to 2001-were aggregated into 10 058 small areas for Scotland. Tests for significant (p<0.05) geographical clustering of suicide were carried out for each period separately. Methods of suicide inside the identified clusters were compared with those in the rest of Scotland. Results: A significant geographical cluster of suicide among young adults was identified in east Glasgow in all three time periods (involving 92, 159, and 245 cases). Compared with the rest of Scotland, significantly more deaths in these clusters were caused by poisoning from liquids or solids over the entire period, but this was not the case in the most recent period (1999 to 2001). All three clusters could be explained by the concentration of socioeconomic deprivation in this part of Scotland. Conclusions: One interpretation of this large, persistent, and statistically significant cluster of suicides among young adults in east Glasgow is that suicide is geographically contagious, but the present results suggest that it is explained by the concentration of deprivation in this area. Suicide prevention strategies targeting at-risk populations living in east Glasgow are necessary to reduce the suicide burden in Scotland.

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  • Antidepressant Dispensing Trends in New Zealand, 2004-2007

    Exeter, Daniel; Robinson, Elizabeth; Wheeler, Amanda (2009)

    Journal article
    The University of Auckland Library

    The aim of the present study was to explore antidepressant dispensing trends in New Zealand over a 3 year period (2004-2007) with a focus on trends by age, gender, ethnicity, District Health Board and type of antidepressant. Prevalence of antidepressant agents dispensed in the years ending June 2004-2005, 2005-2006 and 2006-2007 was calculated separately for the population aged 15-24, 24-44, 45-64 and 65-100 years, (>=65) by gender. The 12 month prevalence of antidepressant dispensing among the total population aged 15-100 years increased from 7.36% in 2004-2005 to 8.21% in 2005-2006 and to 9.39% in 2006-2007 Selective serotonin re-uptake inhibitor (SSRI) and tricyclic antidepres-sants (TCA) accounted for >90% of all antidepressants dispensed each year. SSRIs were more frequently prescribed to young adults (15-24 years) than TCAs, although this relation changed with increasing age. In women aged >=65, TCAs were more commonly dispensed than SSRIs, while among men in the same age group, dispensing patterns were similar for both agents. Age-specific dispensing rates were higher among female than male subjects, and the NZEO combined populations were dispensed signif cantly more antidepressant agents than Mori or Pacific peoples. Considerable regional variations in antidepressant dispensing were found by ethnicity and gender. There are considerable variations in antidepressant dispensing in NZ, and the rate of dispensing has increased over the 3 years of the present study. Further work is required to investigate the different rates of antidepressant dispensing found between ethnic groups. Depression is strongly associated with suicide and the trend of increased dispensing of antidepressants found in the present study should continue to have a positive effect on suicide rates in NZ.

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  • Impact of service failure: The protective layer of customer relationships

    Sajtos, Laszlo; Brodie, Roderick; Whittome, JR (2010)

    Journal article
    The University of Auckland Library

    Although there has been considerable research about service failure in the last 15 years, scholars have only recently started to examine its impact on relational constructs. This study proposes a holistic model that jointly investigates the role of company image and trust in response to service failures and their impact on the customer value-loyalty process across routine and service failure scenarios. Using survey data of a sample of 552 airline customers, the empirical results find evidence of a relational protective layer for the firm. This layer protects the customer value-loyalty process from the negative impact of service failure by exerting a halo effect on customer value and loyalty, which is concurrently magnified by this negative impact. Further analysis also indicates the diverse roles of company image and company trust in service failures, which reveals the coexistence of the buffering and magnifying effects. The findings underline that company image is the most versatile asset of the firm, and it can serve as an indicator of how service failures will affect the company. Company trust, as opposed to its passive role in routine situations, acts like a safety net in service failures by enhancing the customer???s value perception.

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