(-)-CGP12177 increases contractile force through beta1l-adrenoceptors but not through beta3-adrenoceptors in human right atrial myocardium

(-)-CGP12177 is a non-conventional partial agonist that causes modest and transient increases of contractile force in human atrial trabeculae (Kaumann and Molenaar, 2008). These effects are markedly increased and maintained by inhibition of phosphodiesterase PDE3. As verified with recombinant receptors, the cardiostimulant effect of (-)-CGP12177 is mediated through a site at the beta1-adrenoceptor with lower affinity (beta1LAR) compared to the site through which (-)-CGP12177 antagonizes the effects of catecholamines (beta1HAR). However, in a recent report it was proposed that the positive inotropic effects of CGP12177 are mediated through beta3-adrenoceptors (Skeberdis et al 2008). We therefore investigated whether the effects of (-)-CGP12177 on human atrial trabeculae are antagonized by the beta3-adrenoceptor-selective antagonist L-748,337 (1 microM). (-)-CGP12177 (200 nM) caused a stable increase in force which was significantly reduced by the addition of (-)-bupranolol (1 microM), P = 0.002, (basal 4.45 ± 0.78 mN, IBMX (PDE inhibitor) 5.47 ± 1.01 mN, (-)-CGP12177 9.34 ± 1.33 mN, (-)-bupranolol 5.79 ± 1.08 mN, n = 6) but not affected by the addition of L-748,337 (1 microM), P = 0.12, (basal 4.48 ± 1.32 mN, IBMX 7.15 ± 2.28 mN, (-)-CGP12177 12.51 ± 3.71 mN, L-748,337 10.90 ± 3.49 mN, n = 6). Cumulative concentration-effect curves for (-)-CGP12177 were not shifted to the right by L-748,337 (1 microM). The –logEC50M values of (-)-CGP12177 in the absence and presence of L-748,337 were 7.21±0.09 and 7.41±0.13, respectively (data from 25 trabeculae from 8 patients, P=0.2) The positive inotropic effects of (-)-CGP12177 (IBMX present) were not antagonized by L-748,337 but were blunted by (-)-bupranolol (1 microM). The results rule out an involvement of beta3-adrenoceptors in the positive inotropic effects (-)-CGP12177 in human right atrial myocardium and are consistent with mediation through beta1LAR. Kaumann A and Molenaar P (2008) Pharmacol Ther 118, 303-336 Skeberdis VA et al (2008) J Clin Invest, 118, 3219-3227

A decision support system for sustainable urban development : the integrated land use and transportation indexing model

The broad definition of sustainable development at the early stage of its introduction has caused confusion and hesitation among local authorities and planning professionals. The main difficulties are experience in employing loosely-defined principles of sustainable development in setting policies and goals. The question of how this theory/rhetoric-practice gap could be filled will be the theme of this study. One of the widely employed sustainability accounting approaches by governmental organisations, triple bottom line, and applicability of this approach to sustainable urban development policies will be examined. When incorporating triple bottom line considerations with the environmental impact assessment techniques, the framework of GIS-based decision support system that helps decision-makers in selecting policy option according to the economic, environmental and social impacts will be introduced. In order to embrace sustainable urban development policy considerations, the relationship between urban form, travel pattern and socio-economic attributes should be clarified. This clarification associated with other input decision support systems will picture the holistic state of the urban settings in terms of sustainability. In this study, grid-based indexing methodology will be employed to visualise the degree of compatibility of selected scenarios with the designated sustainable urban future. In addition, this tool will provide valuable knowledge about the spatial dimension of the sustainable development. It will also give fine details about the possible impacts of urban development proposals by employing disaggregated spatial data analysis (e.g. land-use, transportation, urban services, population density, pollution, etc.). The visualisation capacity of this tool will help decision makers and other stakeholders compare and select alternative of future urban developments.

Beneficial effects of exercise : shifting the focus from body weight to other markers of health

Background: Exercise is widely promoted as a method of weight management, while the other health benefits are often ignored. The purpose of this study was to examine whether exercise-induced improvements in health are influenced by changes in body weight. Methods: Fifty-eight sedentary overweight/obese men and women (BMI 31.8 (SD 4.5) kg/m2) participated in a 12-week supervised aerobic exercise intervention (70% heart rate max, five times a week, 500 kcal per session). Body composition, anthropometric parameters, aerobic capacity, blood pressure and acute psychological response to exercise were measured at weeks 0 and 12. Results: The mean reduction in body weight was −3.3 (3.63) kg (p<0.01). However, 26 of the 58 participants failed to attain the predicted weight loss estimated from individuals’ exercise-induced energy expenditure. Their mean weight loss was only −0.9 (1.8) kg (p<0.01). Despite attaining a lower-than-predicted weight reduction, these individuals experienced significant increases in aerobic capacity (6.3 (6.0) ml/kg/min; p<0.01), and a decreased systolic (−6.00 (11.5) mm Hg; p<0.05) and diastolic blood pressure (−3.9 (5.8) mm Hg; p<0.01), waist circumference (−3.7 (2.7) cm; p<0.01) and resting heart rate (−4.8 (8.9) bpm, p<0.001). In addition, these individuals experienced an acute exercise-induced increase in positive mood. Conclusions: These data demonstrate that significant and meaningful health benefits can be achieved even in the presence of lower-than-expected exercise-induced weight loss. A less successful reduction in body weight does not undermine the beneficial effects of aerobic exercise. From a public health perspective, exercise should be encouraged and the emphasis on weight loss reduced.

Sunglasses, traffic signals, and color vision deficiencies

Purpose: To determine (a) the effect of different sunglass tint colorations on traffic signal detection and recognition for color normal and color deficient observers, and (b) the adequacy of coloration requirements in current sunglass standards. Methods: Twenty color-normals and 49 color-deficient males performed a tracking task while wearing sunglasses of different colorations (clear, gray, green, yellow-green, yellow-brown, red-brown). At random intervals, simulated traffic light signals were presented against a white background at 5° to the right or left and observers were instructed to identify signal color (red/yellow/green) by pressing a response button as quickly as possible; response times and response errors were recorded. Results: Signal color and sunglass tint had significant effects on response times and error rates (p < 0.05), with significant between-color group differences and interaction effects. Response times for color deficient people were considerably slower than color normals for both red and yellow signals for all sunglass tints, but for green signals they were only noticeably slower with the green and yellow-green lenses. For most of the color deficient groups, there were recognition errors for yellow signals combined with the yellow-green and green tints. In addition, deuteranopes had problems for red signals combined with red-brown and yellow-brown tints, and protanopes had problems for green signals combined with the green tint and for red signals combined with the red-brown tint. Conclusions: Many sunglass tints currently permitted for drivers and riders cause a measurable decrement in the ability of color deficient observers to detect and recognize traffic signals. In general, combinations of signals and sunglasses of similar colors are of particular concern. This is prima facie evidence of a risk in the use of these tints for driving and cautions against the relaxation of coloration limits in sunglasses beyond those represented in the study.

Influence of presbyopic corrections on driving-related eye and head movements

Purpose: To investigate whether wearing different presbyopic vision corrections alters the pattern of eye and head movements when viewing and responding to driving-related traffic scenes. Methods: Participants included 20 presbyopes (mean age: 56.1 ± 5.7 years) who had no experience of wearing presbyopic vision corrections, apart from single vision (SV) reading spectacles. Each participant wore five different vision corrections: distance SV lenses, progressive addition spectacle lenses (PAL), bifocal spectacle lenses (BIF), monovision (MV) and multifocal contact lenses (MTF CL). For each visual condition, participants were required to view videotape recordings of traffic scenes, track a reference vehicle, and identify a series of peripherally presented targets. Digital numerical display panels were also included as near visual stimuli (simulating the visual displays of a vehicle speedometer and radio). Eye and head movements were measured, and the accuracy of target recognition was also recorded. Results: The path length of eye movements while viewing and responding to driving-related traffic scenes was significantly longer when wearing BIF and PAL than MV and MTF CL (both p ≤ 0.013). The path length of head movements was greater with SV, BIF, and PAL than MV and MTF CL (all p < 0.001). Target recognition and brake response times were not significantly affected by vision correction, whereas target recognition was less accurate when the near stimulus was located at eccentricities inferiorly and to the left, rather than directly below the primary position of gaze (p = 0.008), regardless of vision correction. Conclusions: Different presbyopic vision corrections alter eye and head movement patterns. The longer path length of eye and head movements and greater number of saccades associated with the spectacle presbyopic corrections may affect some aspects of driving performance.

Synthesis and characterization of sodalite–polyimide nanocomposite membranes

Nanocomposite membranes are fabricated from sodalite nanocrystals (Sod-N) dispersed in BTDA-MDA polyimide matrices and then characterized structurally and for gas separation. No voids are found upon investigation of the interfacial contact between the inorganic and organic phases, even at a Sod-N loading of up to 35 wt.%. This is due to the functionalization of the zeolite nanocrystals with amino groups (==Si_(CH3)(CH2)3NH2), which covalently link the particles to the polyimide chains in the matrices. The addition of Sod-N increases the hydrogen-gas permeability of the membranes, while nitrogen permeability decreases. Overall, these nanocomposite membranes display substantial selectivity improvements. The sodalite–polyimide membrane containing 35 wt.% Sod-N has a hydrogen permeability of 8.0 Barrers and a H2/N2 ideal selectivity of 281 at 25 C whereas the plain polyimide membrane exhibits a hydrogen permeability of 7.0 Barrers and a H2/N2 ideal selectivity of 198 at the same testing temperature.

Metal oxide nanofibres membranes assembled by spin-coating method

Ceramic membranes are of particular interest in many industrial processes due to their ability to function under extreme conditions while maintaining their chemical and thermal stability. Major structural deficiencies under conventional fabrication approach are pin-holes and cracks, and the dramatic losses of flux when pore sizes are reduced to enhance selectivity. We overcome these structural deficiencies by constructing hierarchically structured separation layer on a porous substrate using larger titanate nanofibres and smaller boehmite nanofibres. This yields a radical change in membrane texture. The differences in the porous supports have no substantial influences on the texture of resulting membranes. The membranes with top layer of nanofibres coated on different porous supports by spin-coating method have similar size of the filtration pores, which is in a range of 10–100 nm. These membranes are able to effectively filter out species larger than 60 nm at flow rates orders of magnitude greater than conventional membranes. The retention can attain more than 95%, while maintaining a high flux rate about 900 L m-2 h. The calcination after spin-coating creates solid linkages between the fibres and between fibres and substrate, in addition to convert boehmite into -alumina nanofibres. This reveals a new direction in membrane fabrication.

Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Clinical efficacy and safety of zoledronic acid in osteoporosis and Paget's disease

Osteoporosis and Paget’s bone disease are the most common diseases of the bone. In addition to glucocorticoid treatment, there are many other secondary causes of osteoporosis. Bisphosphonates are used to treat these bone conditions. Zoledronic acid is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least 1 year following a single intravenous administration. The efficacy and safety of zoledronic acid in the treatment of osteoporosis and Paget’s bone disease are reviewed. This article also covers the studies of the effects of zoledronic acid in the bone loss associated with the secondary osteoporosis.

Early outcomes of patella resurfacing in total knee arthroplasty

Background Patella resurfacing in total knee arthroplasty is a contentious issue. The literature suggests that resurfacing of the patella is based on surgeon preference, and little is known about the role and timing of resurfacing and how this affects outcomes. Methods We analyzed 134,799 total knee arthroplasties using data from the Australian Orthopaedic Association National Joint Replacement Registry. Hazards ratios (HRs) were used to compare rates of early revision between patella resurfacing at the primary procedure (the resurfacing group, R) and primary arthroplasty without resurfacing (no-resurfacing group, NR). We also analyzed the outcomes of NR that were revised for isolated patella addition. Results At 5 years, the R group showed a lower revision rate than the NR group: cumulative per cent revision (CPR) 3.1% and 4.0%, respectively (HR = 0.75, p < 0.001). Revisions for patellofemoral pain were more common in the NR group (17%) than in the R group (1%), and “patella only” revisions were more common in the NR group (29%) than in the R group (6%). Non-resurfaced knees revised for isolated patella addition had a higher revision rate than patella resurfacing at the primary procedure, with a 4-year CPR of 15% and 2.8%, respectively (HR = 4.1, p < 0.001). Interpretation Rates of early revision of primary total knees were higher when the patella was not resurfaced, and suggest that surgeons may be inclined to resurface later if there is patellofemoral pain. However, 15% of non-resurfaced knees revised for patella addition are re-revised by 4 years. Our results suggest an early beneficial outcome for patella resurfacing at primary arthroplasty based on revision rates up to 5 years.

Bifocal lens control of myopia progression in children

This research investigated underlying issues that were critical to the success of the bifocal trial and comprised of three studies. The first study evaluated if Chinese-Canadian children were suitable subjects for the bifocal trial. The high prevalence of myopia in Chinese children suggests that genetic input plays a role in myopia development, but the rapid increase in prevalence over the last few decades indicates environmental factors are also important. Since this bifocal trial was conducted in Canada, this work aimed to determine whether Chinese children who had migrated to Canada would still have high myopia prevalence and a high rate of myopia progression. The second study determined the optimal bifocal lens power for myopia treatment and the effect of incorporating base-in prism into the bifocal. In the majority of published myopia control studies, the power of the prescribed near addition was usually predetermined in the belief that the near addition would always help to improve the near focus. In fact, the effect of near addition on the accommodative error might be quite different even for individuals in which the same magnitude of accommodation lag had been measured. Therefore, this work was necessary to guide the selection of bifocal and prism powers most suitable for the subsequent bifocal trial. The third study, the ultimate goal of this research, was to conduct a longitudinal clinical trial to determine if bifocals and prismatic bifocals could control myopia progression in children.

Action learning of online marketing via a global contest

Introduction: The Google Online Marketing Challenge is a global competition in which student teams run advertising campaigns for small and medium-sized businesses (SMEs) using AdWords, Google’s text-based advertisements. In 2008, its inaugural year, over 8,000 students and 300 instructors from 47 countries representing over 200 schools participated. The Challenge ran in undergraduate and graduate classes in disciplines such as marketing, tourism, advertising, communication and information systems. Combining advertising and education, the Challenge gives student hands-on experience in the increasingly important field of online marketing, engages them with local businesses and motivates them through the thrill of a global competition. Student teams receive US$200 in AdWords credits, Google’s premier advertising product that offers cost-per-click advertisements. The teams then recruit and work with a local business to devise an effective online marketing campaign. Students first outline a strategy, run a series of campaigns, and provide their business with recommendations to improve their online marketing. Teams submit two written reports for judging by 14 academics in eight countries. In addition, Google AdWords experts judge teams on their campaign statistics such as success metrics and account management. Rather than a marketing simulation against a computer or hypothetical marketing plans for hypothetical businesses, the Challenges has student teams develop and manage real online advertising campaigns for their clients and compete against peers globally.

Determining the psychosocial predictors of living, living-related, and posthumous organ donation

The worldwide organ shortage occurs despite people’s positive organ donation attitudes. The discrepancy between attitudes and behaviour is evident in Australia particularly, with widespread public support for organ donation but low donation and communication rates. This problem is compounded further by the paucity of theoretically based research to improve our understanding of people’s organ donation decisions. This program of research contributes to our knowledge of individual decision making processes for three aspects of organ donation: (1) posthumous (upon death) donation, (2) living donation (to a known and unknown recipient), and (3) providing consent for donation by communicating donation wishes on an organ donor consent register (registering) and discussing the donation decision with significant others (discussing). The research program used extended versions of the Theory of Planned Behaviour (TPB) and the Prototype/Willingness Model (PWM), incorporating additional influences (moral norm, self-identity, organ recipient prototypes), to explicate the relationship between people’s positive attitudes and low rates of organ donation behaviours. Adopting the TPB and PWM (and their extensions) as a theoretical basis overcomes several key limitations of the extant organ donation literature including the often atheoretical nature of organ donation research, thefocus on individual difference factors to construct organ donor profiles and the omission of important psychosocial influences (e.g., control perceptions, moral values) that may impact on people’s decision-making in this context. In addition, the use of the TPB and PWM adds further to our understanding of the decision making process for communicating organ donation wishes. Specifically, the extent to which people’s registering and discussing decisions may be explained by a reasoned and/or a reactive decision making pathway is examined (Stage 3) with the novel application of the TPB augmented with the social reaction pathway in the PWM. This program of research was conducted in three discrete stages: a qualitative stage (Stage 1), a quantitative stage with extended models (Stage 2), and a quantitative stage with augmented models (Stage 3). The findings of the research program are reported in nine papers which are presented according to the three aspects of organ donation examined (posthumous donation, living donation, and providing consent for donation by registering or discussing the donation preference). Stage One of the research program comprised qualitative focus groups/interviews with university students and community members (N = 54) (Papers 1 and 2). Drawing broadly on the TPB framework (Paper 1), content analysed responses revealed people’s commonly held beliefs about the advantages and disadvantages (e.g., prolonging/saving life), important people or groups (e.g., family), and barriers and motivators (e.g., a family’s objection to donation), related to living and posthumous organ donation. Guided by a PWM perspective, Paper Two identified people’s commonly held perceptions of organ donors (e.g., altruistic and giving), non-donors (e.g., self-absorbed and unaware), and transplant recipients (e.g., unfortunate, and in some cases responsible/blameworthy for their predicament). Stage Two encompassed quantitative examinations of people’s decision makingfor living (Papers 3 and 4) and posthumous (Paper 5) organ donation, and for registering and discussing donation wishes (Papers 6 to 8) to test extensions to both the TPB and PWM. Comparisons of health students’ (N = 487) motivations and willingness for living related and anonymous donation (Paper 3) revealed that a person’s donor identity, attitude, past blood donation, and knowing a posthumous donor were four common determinants of willingness, with the results highlighting students’ identification as a living donor as an important motive. An extended PWM is presented in Papers Four and Five. University students’ (N = 284) willingness for living related and anonymous donation was tested in Paper Four with attitude, subjective norm, donor prototype similarity, and moral norm (but not donor prototype favourability) predicting students’ willingness to donate organs in both living situations. Students’ and community members’ (N = 471) posthumous organ donation willingness was assessed in Paper Five with attitude, subjective norm, past behaviour, moral norm, self-identity, and prior blood donation all significantly directly predicting posthumous donation willingness, with only an indirect role for organ donor prototype evaluations. The results of two studies examining people’s decisions to register and/or discuss their organ donation wishes are reported in Paper Six. People’s (N = 24) commonly held beliefs about communicating their organ donation wishes were explored initially in a TPB based qualitative elicitation study. The TPB belief determinants of intentions to register and discuss the donation preference were then assessed for people who had not previously communicated their donation wishes (N = 123). Behavioural and normative beliefs were important determinants of registering and discussing intentions; however, control beliefs influenced people’s registering intentions only. Paper Seven represented the first empirical test of the role of organ transplant recipient prototypes (i.e., perceptions of organ transplant recipients) in people’s (N = 465) decisions to register consent for organ donation. Two factors, Substance Use and Responsibility, were identified and Responsibility predicted people’s organ donor registration status. Results demonstrated that unregistered respondents were the most likely to evaluate transplant recipients negatively. Paper Eight established the role of organ donor prototype evaluations, within an extended TPB model, in predicting students’ and community members’ registering (n = 359) and discussing (n = 282) decisions. Results supported the utility of an extended TPB and suggested a role for donor prototype evaluations in predicting people’s discussing intentions only. Strong intentions to discuss donation wishes increased the likelihood that respondents reported discussing their decision 1-month later. Stage Three of the research program comprised an examination of augmented models (Paper 9). A test of the TPB augmented with elements from the social reaction pathway in the PWM, and extensions to these models was conducted to explore whether people’s registering (N = 339) and discussing (N = 315) decisions are explained via a reasoned (intention) and/or social reaction (willingness) pathway. Results suggested that people’s decisions to communicate their organ donation wishes may be better explained via the reasoned pathway, particularly for registering consent; however, discussing also involves reactive elements. Overall, the current research program represents an important step toward clarifying the relationship between people’s positive organ donation attitudes but low rates of organ donation and communication behaviours. Support has been demonstrated for the use of extensions to two complementary theories, the TPB and PWM, which can inform future research aiming to explicate further the organ donation attitude-behaviour relationship. The focus on a range of organ donation behaviours enables the identification of key targets for future interventions encouraging people’s posthumous and living donation decisions, and communication of their organ donation preference.

Same-sex intimate partner violence : exploring the parameters

Intimate partner violence (IPV) is not only a problem for heterosexual couples. Although research in the area is beset by methodological and definitional problems, studies generally demonstrate that IPV also affects those who identify as non-heterosexual; that is, those sexualities that are typically categorized as lesbian, gay, bisexual, transgender, or intersex (LGBTI). IPV appears to be at least as prevalent in LGBTI relationships as it is in heterosexual couples, and follows similar patterns (e.g. Australian Research Centre on Sex, Health and Society 2006; Donovan et al. 2006; Chan 2005; Craft and Serovich 2005; Burke et al. 2002; Jeffries and Ball 2008; Kelly and Warshafsky 1987; Letellier 1994; Turrell 2000; Ristock 2003; Vickers 1996). There is, however, little in the way of specific community or social services support available to either victims or perpetrators of violence in same-sex relationships (see Vickers 1996). In addition, there are important differences in the experience of IPV between LGBTI and non-LGBTI victims, and even among LGBTI individuals; for example, among transgender populations (Chan 2005), and those who are HIV sero-positive (Craft and Serovich 2005). These different experiences of IPV include the use of HIV and the threat of “outing” a partner as tools of control, as just two examples (Jeffries and Ball 2008; Salyer 1999; WA Government 2008b). Such differences impact on how LGBTI victims respond to the violence, including whether or not and how they seek help, what services they are able to avail themselves of, and how likely they are to remain with, or return to, their violent partners (Burke et al. 2002). This chapter explores the prevalent heteronormative discourses that surround IPV, both within the academic literature, and in general social and government discourses. It seeks to understand how same-sex IPV remains largely invisible, and suggests that these dominant discourses play a major role in maintaining this invisibility. In many respects, it builds on work by a number of scholars who have begun to interrogate the criminal justice and social discourses surrounding violent crime, primarily sexual violence, and who problematize these discourses (see for example Carmody 2003; Carmody and Carrington 2000; Marcus 1992). It will begin by outlining these dominant discourses, and then problematize these by identifying some of the important differences between LGBTI IPV and IPV in heterosexual relationships. In doing so, this chapter will suggest some possible reasons for the silence regarding IPV in LGBTI relationships, and the effects that this can have on victims. Although an equally important area of research, and another point at which the limitations of dominant social discourses surrounding IPV can be brought to light, this chapter will not examine violence experienced by heterosexual men at the hands of their intimate female partners. Instead, it will restrict itself to IPV perpetrated within same-sex relationships.

A role mining inspired approach to representing user behaviour in ERP systems

Despite all attempts to prevent fraud, it continues to be a major threat to industry and government. Traditionally, organizations have focused on fraud prevention rather than detection, to combat fraud. In this paper we present a role mining inspired approach to represent user behaviour in Enterprise Resource Planning (ERP) systems, primarily aimed at detecting opportunities to commit fraud or potentially suspicious activities. We have adapted an approach which uses set theory to create transaction profiles based on analysis of user activity records. Based on these transaction profiles, we propose a set of (1) anomaly types to detect potentially suspicious user behaviour and (2) scenarios to identify inadequate segregation of duties in an ERP environment. In addition, we present two algorithms to construct a directed acyclic graph to represent relationships between transaction profiles. Experiments were conducted using a real dataset obtained from a teaching environment and a demonstration dataset, both using SAP R/3, presently the most predominant ERP system. The results of this empirical research demonstrate the effectiveness of the proposed approach.