Long terminal repeats act as androgen-responsive enhancers for the PSA-Kallikrein locus

The androgen receptor (AR) signaling pathway is a common therapeutic target for prostate cancer, because it is critical for the survival of both hormone-responsive and castrate-resistant tumor cells. Most of the detailed understanding that we have of AR transcriptional activation has been gained by studying classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate-specific antigen) has been used as a prototypical AR target gene, because it is highly androgen responsive in prostate cancer cells. Three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation. Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes at the centromeric end of the kallikrein locus with enhancers that evolved from the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand-dependent recruitment of the AR to individual LTR-derived enhancers results in concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP prostate cancer cells. At the molecular level, a kallikrein-specific duplication within the LTR is required for maximal androgen responsiveness. Therefore, KLK3 represents a subset of target genes regulated by repetitive elements but is not typical of the whole spectrum of androgen-responsive transcripts. These data provide a novel and more detailed understanding of AR transcriptional activation and emphasize the importance of repetitive elements as functional regulatory units

Effect of cold water immersion after exercise in the heat on muscle function, body temperatures, and vessel diameter

Cold water immersion (CWI) is a popular recovery modality, but actual physiological responses to CWI after exercise in the heat have not been well documented. The purpose of this study was to examine effects of 20-min CWI (14 degrees C) on neuromuscular function, rectal (T(re)) and skin temperature (T(sk)), and femoral venous diameter after exercise in the heat. Ten well-trained male cyclists completed two bouts of exercise consisting of 90-min cycling at a constant power output (216+/-12W) followed by a 16.1km time trial (TT) in the heat (32 degrees C). Twenty-five minutes post-TT, participants were assigned to either CWI or control (CON) recovery conditions in a counterbalanced order. T(re) and T(sk) were recorded continuously, and maximal voluntary isometric contraction torque of the knee extensors (MVIC), MVIC with superimposed electrical stimulation (SMVIC), and femoral venous diameters were measured prior to exercise, 0, 45, and 90min post-TT. T(re) was significantly lower in CWI beginning 50min post-TT compared with CON, and T(sk) was significantly lower in CWI beginning 25min post-TT compared with CON. Decreases in MVIC, and SMVIC torque after the TT were significantly greater for CWI compared with CON; differences persisted 90min post-TT. Femoral vein diameter was approximately 9% smaller for CWI compared with CON at 45min post-TT. These results suggest that CWI decreases T(re), but has a negative effect on neuromuscular function.

The effect of overnight sleep deprivation after competitive rugby league matches on postmatch physiological and perceptual recovery

PURPOSE: This study examined the effects of overnight sleep deprivation on recovery following competitive rugby league matches. METHODS: Eleven male, amateur rugby league players performed two competitive matches, followed by either a normal night's sleep (~8h; CONT) or a sleep deprived night (~0h; SDEP) in a randomised fashion. Testing was conducted the morning of the match, and immediately post-match, 2h post and the next morning (16h post-match). Measures included counter-movement jump (CMJ) distance, knee extensor maximal voluntary contraction (MVC), voluntary activation (VA), venous blood creatine kinase (CK) and C-reactive protein (CRP), perceived muscle soreness and a word-colour recognition cognitive function test. Percent change between post- and 16h post-match was reported to determine the effect of the intervention the next morning. RESULTS: Large effects indicated a greater post- to 16h post-match percentage decline in CMJ distance following SDEP compared to CONT (P=0.10-0.16; d=0.95-1.05). Similarly, the percentage decline in incongruent word-colour reaction times were increased in SDEP trials (P=0.007; d=1.75). Measures of MVC did not differ between conditions (P=0.40-0.75; d=0.13-0.33), though trends for larger percentage decline in VA were detected in SDEP (P=0.19; d=0.84). Further, large effects indicated higher CK and CRP responses 16h post-match during SDEP compared to CONT (P=0.11-0.87; d=0.80-0.88). CONCLUSIONS: Sleep deprivation negatively affected recovery following a rugby league match, specifically impairing CMJ distance and cognitive function. Practitioners should promote adequate post-match sleep patterns or adjust training demands the next day to accommodate the altered physical and cognitive state following sleep deprivation.

ECMO : the clinician’s view

Background: Extra corporeal membrane oxygenation (ECMO) is a complex rescue therapy used to provide cardiac and/or respiratory support for critically ill patients who have failed maximal conventional medical management. ECMO is based on a modified cardiopulmonary bypass (CPB) circuit, and can provide cardiopulmonary support for up-to several months. It can be used in a veno venous configuration for isolated respiratory failure, (VV-ECMO), or in a veno arterial configuration (VA-ECMO) where support is necessary for cardiac +/- respiratory failure. The ECMO circuit consists of five main components: large bore cannulae (access cannulae) for drainage of the venous system, and return cannulae to either the venous (in VV-ECMO) or arterial (in VA ECMO) system. An oxygenator, with a vast surface area of hollow filaments, allows addition of oxygen and removal of carbon dioxide; a centrifugal blood pump allows propulsion of blood through the circuit at upto 10 L/minute; a control module and a thermoregulatory unit, which allows for exact temperature control of the extra corporeal blood. Methods: The first successful use of ECMO for ARDS in adults occurred in 1972, and its use has become more commonplace over the last 30 years, supported by the improvement in design and biocompatibility of the equipment, which has reduced the morbidity associated with this modality. Whilst the use of ECMO in neonatal population has been supported by numerous studies, the evidence upon which ECMO was integrated into adult practice was substantially less robust. Results: Recent data, including the CESAR study (Conventional Ventilatory Support versus Extra corporeal membrane oxygenation for Severe Respiratory failure) has added a degree of evidence to the role of ECMO in such a patient population. The CESAR study analysed 180 patients, and confirmed that ECMO was associated with an improved rate of survival. More recently, ECMO has been utilized in numerous situations within the critical care area, including support in high-risk percutaneous interventions in cardiac catheter lab; the operating room, emergency department, as well in specialized inter-hospital retrieval services. The increased understanding of the risk:benefit profile of ECMO, along with a reduction in morbidity associated with its use will doubtless lead to a substantial rise in the utilisation of this modality. As with all extra-corporeal circuits, ECMO opposes the basic premises of the mammalian inflammation and coagulation cascade where blood comes into foreign circulation, both these cascades are activated. Anti-coagulation is readily dealt with through use of agents such as heparin, but the inflammatory excess, whilst less macroscopically obvious, continues un-abated. Platelet consumption and neutrophil activation occur rapidly, and the clinician is faced with balancing the need of anticoagulation for the circuit, against haemostasis in an acutely bleeding patient. Alterations in pharmacokinetics may result in inadequate levels of disease modifying therapeutics, such as antibiotics, hence paradoxically delaying recovery from conditions such as pneumonia. Key elements of nutrition and the innate immune system maysimilarly be affected. Summary: This presentation will discuss the basic features of ECMO to the nonspecialist, and review the clinical conundrum faced by the team treating these most complex cases.

Developing intercultural competence in pre-service teachers from Australia and Malaysia : insights from the “Patches” programme

Developing intercultural competence in pre-service teachers from Australia and Malaysia: Insights from a Patches program. Innovative pedagogies can offer pre-service teachers the opportunity to develop their intercultural competence and take up more globalised viewpoints. One such innovation is the Patches program which brought together Malaysian and Australian pre-service teachers who were studying at the same university in Brisbane, Australia, to actively explore issues of cultural and linguistic difference. The participants were 14 Australian fourth-year pre-service teachers who were enrolled in a program on inclusive education, and 58 Malaysian pre-service teachers who had recently arrived at the university in Brisbane to commence their second year of an international education program. In peer groupings, these domestic and international pre-service teachers engaged in a series of interactive tasks and reflective writing workshops exploring intercultural experiences, over a period of ten weeks. Each element or ‘patch’ in the program was designed to build up into a mosaic of intercultural learning. The flexible structuring of the Patches Program provided a supportive framework for participant interaction whilst allowing the groups to decide for themselves the nature and extent of their involvement in a series of community-related tasks. The process of negotiating and implementing these activities formed the basis for establishing meaningful relationships between the participants. The development of the participants’ intercultural competence is traced through their reflective narratives and focus group discussions, drawing on Byram’s concept of the five savoirs. Explaining aspects of Australian culture to their newly arrived Malaysian peers, allowed the Australian pre-service teachers to take a perspective of outsideness towards their own familiar social practices. In addition, being unusually positioned as the linguistic other amongst a group of Bahasa Melayu speakers, highlighted for the Australian pre-service teachers the importance of being inclusive. For the Malaysian pre-service teachers, participation in the Patches program helped to extend intercultural understandings, establish social networks with local students, and build a sense of community in their new learning environment. Both groups of pre-service teachers noted the power of “learning directly by interacting rather than through books”. In addition to interacting interculturally, the process of reflecting on these intercultural experiences is seen as integral to the development of intercultural competence.

Experimental and computer simulation validation of ultrasound phase interference created by lateral inhomogeneity of transit time in replica bone marrow composite models

Purpose: The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone for the assessment of osteoporosis follows a parabolic-type dependence with bone volume fraction; having minima values corresponding to both entire bone and entire marrow. Langton has recently proposed that the primary BUA mechanism may be significant phase interference due to variations in propagation transit time through the test sample as detected over the phase-sensitive surface of the receive ultrasound transducer. This fundamentally simple concept assumes that the propagation of ultrasound through a complex solid : liquid composite sample such as cancellous bone may be considered by an array of parallel ‘sonic rays’. The transit time of each ray is defined by the proportion of bone and marrow propagated, being a minimum (tmin) solely through bone and a maximum (tmax) solely through marrow. A Transit Time Spectrum (TTS), ranging from tmin to tmax, may be defined describing the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit time over the surface of the receive ultrasound transducer. Phase interference may result from interaction of ‘sonic rays’ of differing transit times. The aim of this study was to test the hypothesis that there is a dependence of phase interference upon the lateral inhomogenity of transit time by comparing experimental measurements and computer simulation predictions of ultrasound propagation through a range of relatively simplistic solid:liquid models exhibiting a range of lateral inhomogeneities. Methods: A range of test models was manufactured using acrylic and water as surrogates for bone and marrow respectively. The models varied in thickness in one dimension normal to the direction of propagation, hence exhibiting a range of transit time lateral inhomogeneities, ranging from minimal (single transit time) to maximal (wedge; ultimately the limiting case where each sonic ray has a unique transit time). For the experimental component of the study, two unfocused 1 MHz ¾” broadband diameter transducers were utilized in transmission mode; ultrasound signals were recorded for each of the models. The computer simulation was performed with Matlab, where the transit time and relative amplitude of each sonic ray was calculated. The transit time for each sonic ray was defined as the sum of transit times through acrylic and water components. The relative amplitude considered the reception area for each sonic ray along with absorption in the acrylic. To replicate phase-sensitive detection, all sonic rays were summed and the output signal plotted in comparison with the experimentally derived output signal. Results: From qualtitative and quantitative comparison of the experimental and computer simulation results, there is an extremely high degree of agreement of 94.2% to 99.0% between the two approaches, supporting the concept that propagation of an ultrasound wave, for the models considered, may be approximated by a parallel sonic ray model where the transit time of each ray is defined by the proportion of ‘bone’ and ‘marrow’. Conclusions: This combined experimental and computer simulation study has successfully demonstrated that lateral inhomogeneity of transit time has significant potential for phase interference to occur if a phase-sensitive ultrasound receive transducer is implemented as in most commercial ultrasound bone analysis devices.

The structured phase of concurrency

This extended abstract summarizes the state-of-the-art solution to the structuring problem for models that describe existing real world or envisioned processes. Special attention is devoted to models that allow for the true concurrency semantics. Given a model of a process, the structuring problem deals with answering the question of whether there exists another model that describes the process and is solely composed of structured patterns, such as sequence, selection, option for simultaneous execution, and iteration. Methods and techniques for structuring developed by academia as well as products and standards proposed by industry are discussed. Expectations and recommendations on the future advancements of the structuring problem are suggested.

Carbohydrate supplementation and alterations in neutrophils, and plasma cortisol and myoglobin concentration after intense exercise

The present study examined the effect of carbohydrate supplementation on changes in neutrophil counts, and the plasma concentrations of cortisol and myoglobin after intense exercise. Eight well-trained male runners ran on a treadmill for 1 h at 85% maximal oxygen uptake on two separate occasions. In a double-blind cross-over design, subjects consumed either 750 ml of a 10% carbohydrate (CHO) drink or a placebo drink on each occasion. The order of the trials was counter-balanced. Blood was drawn immediately before and after exercise, and 1 h after exercise. Immediately after exercise, neutrophil counts (CHO, 49%; placebo, 65%; P<0.05), plasma concentrations of glucose (CHO, 43%; P<0.05), lactate (CHO, 130%; placebo, 130%; P<0.01), cortisol (CHO, 100%; placebo, 161%; P<0.01), myoglobin (CHO, 194%; placebo, 342%; P<0.01) all increased significantly. One hour post-exercise, plasma myoglobin concentration (CHO, 331%; placebo, 482%; P<0.01) and neutrophil count (CHO, 151%; placebo, 230% P<0.01) both increased further above baseline. CHO significantly attenuated plasma myoglobin concentration and the neutrophil count after exercise (P<0.01), but did not affect plasma cortisol concentration. The effects of CHO on plasma myoglobin concentration may be due to alterations in cytokine synthesis, insulin responses or myoglobin clearance rates from the bloodstream during exercise. Plasma cortisol responses to CHO during exercise may depend on the intensity of exercise, or the amount of CHO consumed. Lastly, cortisol appears to play a minor role in the mobilisation of neutrophils after intense exercise.

Changes in neutrophil surface receptor expression, degranulation, and respiratory burst activity after moderate- and high-intensity exercise

Intense exercise stimulates the systemic release of a variety of factors that alter neutrophil surface receptor expression and functional activity. These alterations may influence resistance to infection after intense exercise. The aim of this study was to examine the influence of exercise intensity on neutrophil receptor expression, degranulation (measured by plasma and intracellular myeloperoxidase concentrations), and respiratory burst activity. Ten well-trained male runners ran on a treadmill for 60 min at 60% [moderate-intensity exercise (MI)] and 85% maximal oxygen consumption [high-intensity exercise (HI)]. Blood was drawn immediately before and after exercise and at 1 h postexercise. Immediately after HI, the expression of the neutrophil receptor CD16 was significantly below preexercise values (P < 0.01), whereas MI significantly reduced CD35 expression below preexercise values (P < 0.05). One hour after exercise at both intensities, there was a significant decline in CD11b expression (P < 0.05) and a further decrease in CD16 expression compared with preexercise values (P < 0.01). CD16 expression was lower 1 h after HI than 1 h after MI (P < 0.01). Immediately after HI, intracellular myeloperoxidase concentration was less than preexercise values (P < 0.01), whereas plasma myeloperoxidase concentration was greater (P < 0.01), indicating that HI stimulated neutrophil degranulation. Plasma myeloperoxidase concentration was higher immediately after HI than after MI (P < 0.01). Neutrophil respiratory burst activity increased after HI (P < 0.01). In summary, both MI and HI reduced neutrophil surface receptor expression. Although CD16 expression was reduced to a greater extent after HI, this reduction did not impair neutrophil degranulation and respiratory burst activity.

Changes in Knee Biomechanics After a Hip-Abductor Strengthening Protocol for Runners With Patellofemoral Pain Syndrome

Context: Very few authors have investigated the relationship between hip-abductor muscle strength and frontal-plane knee mechanics during running. Objective: To investigate this relationship using a 3-week hip-abductor muscle-strengthening program to identify changes in strength, pain, and biomechanics in runners with patellofemoral pain syndrome (PFPS). Design: Cohort study. Setting: University-based clinical research laboratory. Patients or Other Participants: Fifteen individuals (5 men, 10 women) with PFPS and 10 individuals without PFPS (4 men, 6 women) participated. Intervention(s): The patients with PFPS completed a 3-week hip-abductor strengthening protocol; control participants did not. Main Outcome Measure(s): The dependent variables of interest were maximal isometric hip-abductor muscle strength, 2-dimensional peak knee genu valgum angle, and stride-to-stride knee-joint variability. All measures were recorded at baseline and 3 weeks later. Between-groups differences were compared using repeated-measures analyses of variance. Results: At baseline, the PFPS group exhibited reduced strength, no difference in peak genu valgum angle, and increased stride-to-stride knee-joint variability compared with the control group. After the 3-week protocol, the PFPS group demonstrated increased strength, less pain, no change in peak genu valgum angle, and reduced stride-to-stride knee-joint variability compared with baseline. Conclusions: A 3-week hip-abductor muscle-strengthening protocol was effective in increasing muscle strength and decreasing pain and stride-to-stride knee-joint variability in individuals with PFPS. However, concomitant changes in peak knee genu valgum angle were not observed.

The relationship between hip-abductor strength and the magnitude of pelvic drop in patients with low back pain

Context: It has been theorized that a positive Trendelenburg test (TT) indicates weakness of the stance hip-abductor (HABD) musculature, results in contralateral pelvic drop, and represents impaired load transfer, which may contribute to low back pain. Few studies have tested whether weakness of the HABDs is directly related to the magnitude of pelvic drop (MPD). Objective: To examine the relationship between HABD strength and MPD during the static TT and during walking for patients with nonspecific low back pain (NSLBP) and healthy controls (CON). A secondary purpose was to examine this relationship in NSLBP after a 3-wk HABD-strengthening program. Design: Quasi-experimental. Setting: Clinical research laboratory. Participants: 20 (10 NSLBP and 10 CON). Intervention: HABD strengthening. Main Outcome Measures: Normalized HABD strength, MPD during TT, and maximal pelvic frontal-plane excursion during walking. Results: At baseline, the NSLBP subjects were significantly weaker (31%; P = .03) than CON. No differences in maximal pelvic frontal-plane excursion (P = .72), right MPD (P = 1.00), or left MPD (P = .40) were measured between groups. During the static TT, nonsignificant correlations were found between left HABD strength and right MPD for NSLBP (r = -.32, P = .36) and CON (r = -.24, P = .48) and between right HABD strength and left MPD for NSLBP (r = -.24, P = .50) and CON (r = -.41, P = .22). Nonsignificant correlations were found between HABD strength and maximal pelvic frontal-plane excursion for NSLBP (r = -.04, P = .90) and CON (r = -.14, P = .68). After strengthening, NSLBP demonstrated significant increases in HABD strength (12%; P = .02), 48% reduction in pain, and no differences in MPD during static TT and maximal pelvic frontal-plane excursion compared with baseline. Conclusions: HABD strength was poorly correlated to MPD during the static TT and during walking in CON and NSLBP. The results suggest that HABD strength may not be the only contributing factor in controlling pelvic stability, and the static TT has limited use as a measure of HABD function.

The relationship between hip abductor muscle strength and magnitude of pelvic drop following a 3 week strengthening protocol in non-specific low back pain patients.

Purpose: To examine the relationship between hip abductor muscle (HABD) strength and the magnitude of pelvic drop (MPD) for patients with non-specific low back pain (NSLBP) and controls (CON) prior to and following a 3-week HABD strengthening protocol. At baseline, we hypothesized that NSLBP patients would exhibit reduced HABD strength and greater MPD compared to CON. Following the protocol, we hypothesized that strength would increase and MPD would decrease. Relevance: The Trendelenburg test (TT) is a common clinical test used to examine the ability of the HABD to maintain horizontal pelvic position during single limb stance. However, no study has specifically tested this theory. Moreover, no study has investigated the relationship between HABD strength and pelvic motion during walking or tested whether increased HABD strength would reduce the MPD. Methods: Quasi-experimental with 3-week exercise intervention. Fifteen NSLBP patients (32.5yrs,range 21-51yrs; VAS baseline: 5.3cm) and 10 CON (29.5yrs,range 22-47yrs) were recruited. Isometric HABD strength was measured using a force dynamometer and the average of three maximal voluntary contractions were normalized to body mass (N/kg). Two-dimensional MPD (degrees) was measured using a 60 Hz camera and was derived from two retroreflective-markers placed on the posterior superior iliac spines. MPD was measured while performing the static TT and while walking and averaged over 10 consecutive footfalls. NSLBP patients completed a 3-week HABD strengthening protocol consisting of 2 open-kinetic-chain exercises then all measures were repeated. Non-parametric analysis was used for group comparisons and correlation analysis. Results: At baseline, the NSLBP patients demonstrated 31% reduced HABD strength (mean=6.6 N/kg) compared to CON (mean=9.5 N/kg: p=0.03) and no significant differences in maximal pelvic frontal plane excursion while walking (NSLBP:mean=8.1°, CON:mean=7.1°: p=0.72). No significant correlations were measured between left HABD strength and right MPD (r=-0.37, p=0.11), or between right HABD strength and left MPD (r=-0.04, p=0.84) while performing the static TT. Following the 3-week strengthening protocol, NSLBP patients demonstrated a 12% improvement in strength (Post:mean=7.4 N/kg: p=0.02), a reduction in pain (VAS followup: 2.8cm), but no significant decreases in MPD while walking (p=0.92). Conclusions: NSLBP patients demonstrated reduced HABD strength at baseline and were able to increase strength and reduce pain in a 3-week period. However, despite increases in HABD strength, the NSLBP group exhibited similar MPD motion during the static TT and while walking compared to baseline and controls. Implications: The results suggest that the HABD alone may not be primarily responsible for controlling a horizontal pelvic position during static and dynamic conditions. Increasing the strength of the hip abductors resulted in a reduction of pain in NSLBP patients providing evidence for further research to identify specific musculature responsible for controlling pelvic motion.

How to achieve maximum charge carrier loading on heteroatom-substituted graphene nanoribbon edges: density functional theory study

The practical number of charge carriers loaded is crucial to the evaluation of the capacity performance of carbon-based electrodes in service, and cannot be easily addressed experimentally. In this paper, we report a density functional theory study of charge carrier adsorption onto zigzag edge-shaped graphene nanoribbons (ZGNRs), both pristine and incorporating edge substitution with boron, nitrogen or oxygen atoms. All edge substitutions are found to be energetically favorable, especially in oxidized environments. The maximal loading of protons onto the substituted ZGNR edges obeys a rule of [8-n-1], where n is the number of valence electrons of the edge-site atom constituting the adsorption site. Hence, a maximum charge loading is achieved with boron substitution. This result correlates in a transparent manner with the electronic structure characteristics of the edge atom. The boron edge atom, characterized by the most empty p band, facilitates more than the other substitutional cases the accommodation of valence electrons transferred from the ribbon, induced by adsorption of protons. This result not only further confirms the possibility of enhancing charge storage performance of carbon-based electrochemical devices through chemical functionalization but also, more importantly, provides the physical rationale for further design strategies.

Coordinated probabilistic optimal decision-making model for multi-area ATC with risk control

In the decision-making of multi-area ATC (Available Transfer Capacity) in electricity market environment, the existing resources of transmission network should be optimally dispatched and coordinately employed on the premise that the secure system operation is maintained and risk associated is controllable. The non-sequential Monte Carlo simulation is used to determine the ATC probability density distribution of specified areas under the influence of several uncertainty factors, based on which, a coordinated probabilistic optimal decision-making model with the maximal risk benefit as its objective is developed for multi-area ATC. The NSGA-II is applied to calculate the ATC of each area, which considers the risk cost caused by relevant uncertainty factors and the synchronous coordination among areas. The essential characteristics of the developed model and the employed algorithm are illustrated by the example of IEEE 118-bus test system. Simulative result shows that, the risk of multi-area ATC decision-making is influenced by the uncertainties in power system operation and the relative importance degrees of different areas.

Identification and evaluation of service bundles for governmental one-stop portals

Recent advances in the area of ‘Transformational Government’ position the citizen at the centre of focus. This paradigm shift from a department-centric to a citizen-centric focus requires governments to re-think their approach to service delivery, thereby decreasing costs and increasing citizen satisfaction. The introduction of franchises as a virtual business layer between the departments and their citizens is intended to provide a solution. Franchises are structured to address the needs of citizens independent of internal departmental structures. For delivering services online, governments pursue the development of a One-Stop Portal, which structures information and services through those franchises. Thus, each franchise can be mapped to a specific service bundle, which groups together services that are deemed to be of relevance to a specific citizen need. This study focuses on the development and evaluation of these service bundles. In particular, two research questions guide the line of investigation of this study: Research Question 1): What methods can be used by governments to identify service bundles as part of governmental One-Stop Portals? Research Question 2): How can the quality of service bundles in governmental One-Stop Portals be evaluated? The first research question asks about the identification of suitable service bundle identification methods. A literature review was conducted, to, initially, conceptualise the service bundling task, in general. As a consequence, a 4-layer model of service bundling and a morphological box were created, detailing characteristics that are of relevance when identifying service bundles. Furthermore, a literature review of Decision-Support Systems was conducted to identify approaches of relevance in different bundling scenarios. These initial findings were complemented by targeted studies of multiple leading governments in the e-government domain, as well as with a local expert in the field. Here, the aim was to identify the current status of online service delivery and service bundling in practice. These findings led to the conceptualising of two service bundle identification methods, applicable in the context of Queensland Government: On the one hand, a provider-driven approach, based on service description languages, attributes, and relationships between services was conceptualised. As well, a citizen-driven approach, based on analysing the outcomes from content identification and grouping workshops with citizens, was also conceptualised. Both methods were then applied and evaluated in practice. The conceptualisation of the provider-driven method for service bundling required the initial specification of relevant attributes that could be used to identify similarities between services called relationships; these relationships then formed the basis for the identification of service bundles. This study conceptualised and defined seven relationships, namely ‘Co-location’, ‘Resource’, ‘Co-occurrence’, ‘Event’, ‘Consumer’, ‘Provider’, and ‘Type’. The relationships, and the bundling method itself, were applied and refined as part of six Action Research cycles in collaboration with the Queensland Government. The findings show that attributes and relationships can be used effectively as a means for bundle identification, if distinct decision rules are in place to prescribe how services are to be identified. For the conceptualisation of the citizen-driven method, insights from the case studies led to the decision to involve citizens, through card sorting activities. Based on an initial list of services, relevant for a certain franchise, participating citizens grouped services according to their liking. The card sorting activity, as well as the required analysis and aggregation of the individual card sorting results, was analysed in depth as part of this study. A framework was developed that can be used as a decision-support tool to assist with the decision of what card sorting analysis method should be utilised in a given scenario. The characteristic features associated with card sorting in a government context led to the decision to utilise statistical analysis approaches, such as cluster analysis and factor analysis, to aggregate card sorting results. The second research question asks how the quality of service bundles can be assessed. An extensive literature review was conducted focussing on bundle, portal, and e-service quality. It was found that different studies use different constructs, terminology, and units of analysis, which makes comparing these models a difficult task. As a direct result, a framework was conceptualised, that can be used to position past and future studies in this research domain. Complementing the literature review, interviews conducted as part of the case studies with leaders in e-government, indicated that, typically, satisfaction is evaluated for the overall portal once the portal is online, but quality tests are not conducted during the development phase. Consequently, a research model which appropriately defines perceived service bundle quality would need to be developed from scratch. Based on existing theory, such as Theory of Reasoned Action, Expectation Confirmation Theory, and Theory of Affordances, perceived service bundle quality was defined as an inferential belief. Perceived service bundle quality was positioned within the nomological net of services. Based on the literature analysis on quality, and on the subsequent work of a focus group, the hypothesised antecedents (descriptive beliefs) of the construct and the associated question items were defined and the research model conceptualised. The model was then tested, refined, and finally validated during six Action Research cycles. Results show no significant difference in higher quality or higher satisfaction among users for either the provider-driven method or for the citizen-driven method. The decision on which method to choose, it was found, should be based on contextual factors, such as objectives, resources, and the need for visibility. The constructs of the bundle quality model were examined. While the quality of bundles identified through the citizen-centric approach could be explained through the constructs ‘Navigation’, ‘Ease of Understanding’, and ‘Organisation’, bundles identified through the provider-driven approach could be explained solely through the constructs ‘Navigation’ and ‘Ease of Understanding’. An active labelling style for bundles, as part of the provider-driven Information Architecture, had a larger impact on ‘Quality’ than the topical labelling style used in the citizen-centric Information Architecture. However, ‘Organisation’, reflecting the internal, logical structure of the Information Architecture, was a significant factor impacting on ‘Quality’ only in the citizen-driven Information Architecture. Hence, it was concluded that active labelling can compensate for a lack of logical structure. Further studies are needed to further test this conjecture. Such studies may involve building alternative models and conducting additional empirical research (e.g. use of an active labelling style for the citizen-driven Information Architecture). This thesis contributes to the body of knowledge in several ways. Firstly, it presents an empirically validated model of the factors explaining and predicting a citizen’s perception of service bundle quality. Secondly, it provides two alternative methods that can be used by governments to identify service bundles in structuring the content of a One-Stop Portal. Thirdly, this thesis provides a detailed narrative to suggest how the recent paradigm shift in the public domain, towards a citizen-centric focus, can be pursued by governments; the research methodology followed by this study can serve as an exemplar for governments seeking to achieve a citizen-centric approach to service delivery.