896 resultados para reservation targets


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There is an urgent need to develop safe, effective, dual-purpose contraceptive agents that combine the prevention of pregnancy with protection against sexually transmitted diseases. Here we report the identification of a group of compounds that on contact with human spermatozoa induce a state of “spermostasis,” characterized by the extremely rapid inhibition of sperm movement without compromising cell viability. These spermostatic agents were more active and significantly less toxic than the reagent in current clinical use, nonoxynol 9, giving therapeutic indices (ratio of spermostatic to cytotoxic activity) that were orders of magnitude greater than this traditional spermicide. Although certain compounds could trigger reactive oxygen species generation by spermatozoa, this activity was not correlated with spermostasis. Rather, the latter was associated with alkylation of two major sperm tail proteins that were identified as A Kinase-Anchoring Proteins (AKAP3 and AKAP4) by mass spectrometry. As a consequence of disrupted AKAP function, the abilities of cAMP to drive protein kinase A-dependent activities in the sperm tail, such as the activation of SRC and the consequent stimulation of tyrosine phosphorylation, were suppressed. Furthermore, analysis of microbicidal activity using Chlamydia muridarum revealed powerful inhibitory effects at the same low micromolar doses that suppressed sperm movement. In this case, the microbicidal action was associated with alkylation of Major Outer Membrane Protein (MOMP), a major chlamydial membrane protein. Taken together, these results have identified for the first time a novel set of cellular targets and chemical principles capable of providing simultaneous defense against both fertility and the spread of sexually transmitted disease.

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We examined properties of culture-level personality traits in ratings of targets (N=5,109) ages 12 to 17 in 24 cultures. Aggregate scores were generalizable across gender, age, and relationship groups and showed convergence with culture-level scores from previous studies of self-reports and observer ratings of adults, but they were unrelated to national character stereotypes. Trait profiles also showed cross-study agreement within most cultures, 8 of which had not previously been studied. Multidimensional scaling showed that Western and non-Western cultures clustered along a dimension related to Extraversion. A culture-level factor analysis replicated earlier findings of a broad Extraversion factor but generally resembled the factor structure found in individuals. Continued analysis of aggregate personality scores is warranted.

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Background Chlamydia pneumoniae is a widespread pathogen causing upper and lower respiratory tract infections in addition to a range of other diseases in humans and animals. Previous whole genome analyses have focused on four essentially clonal (> 99% identity) C. pneumoniae human genomes (AR39, CWL029, J138 and TW183), providing relatively little insight into strain diversity and evolution of this species. Results We performed individual gene-by-gene comparisons of the recently sequenced C. pneumoniae koala genome and four C. pneumoniae human genomes to identify species-specific genes, and more importantly, to gain an insight into the genetic diversity and evolution of the species. We selected genes dispersed throughout the chromosome, representing genes that were specific to C. pneumoniae, genes with a demonstrated role in chlamydial biology and/or pathogenicity (n = 49), genes encoding nucleotide salvage or amino acid biosynthesis proteins (n = 6), and extrachromosomal elements (9 plasmid and 2 bacteriophage genes). Conclusions We have identified strain-specific differences and targets for detection of C. pneumoniae isolates from both human and animal origin. Such characterisation is necessary for an improved understanding of disease transmission and intervention.

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The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.

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Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

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In Australia, trials conducted as 'electronic trials' have ordinarily run with the assistance of commercial service providers, with the associated costs being borne by the parties. However, an innovative approach has been taken by the courts in Queensland. In October 2007 Queensland became the first Australian jurisdiction to develop its own court-provided technology, to facilitate the conduct of an electronic trial. This technology was first used in the conduct of civil trials. The use of the technology in the civil sphere highlighted its benefits and, more significantly, demonstrated the potential to achieve much greater efficiencies. The Queensland courts have now gone further, using the court-provided technology in the high proffle criminal trial of R v Hargraves, Hargraves and Stoten, in which the three accused were tried for conspiracy to defraud the Commonwealth of Australia of about $3.7 million in tax. This paper explains the technology employed in this case and reports on the perspectives of all of the participants in the process. The representatives for all parties involved in this trial acknowledged, without reservation, that the use of the technology at trial produced considerable overall efficiencies and costs savings. The experience in this trial also demonstrates that the benefits of trial technology for the criminal justice process are greater than those for civil litigation. It shows that, when skilfully employed, trial technology presents opportunities to enhance the fairness of trials for accused persons. The paper urges governments, courts and the judiciary in all jurisdictions to continue their efforts to promote change, and to introduce mechanisms to facilitate more broadly a shift from the entrenched paper-based approach to both criminal and civil procedure to one which embraces more broadly the enormous benefits trial technology has to offer.

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Quality, as well as project success, in construction projects should be capable of being regarded as the fulfillment of expectation of those contributors and stakeholders involved in such projects. Although a significant amount of quality practices have been introduced within the industry, establishment and attainment of reasonable levels of quality internationally in construction projects continues to be an ongoing problem. To date, some investigation into the introduction and improvement of quality practices and stakeholder management in the construction industry has been accomplished independently, but so far no major studies have been completed that examine comprehensively how quality management practices that particularly concentrate on the stakeholders’ perspective of quality can be used to contribute to final project quality outcomes. This paper aims to examine the process for development of a framework for better involvement of stakeholders in quality planning and practices and subsequently to contribute to higher quality outcomes within construction projects. Through extensive literature review it highlights various perceptions of quality, categorizes quality issues with particular focus on benefits and shortcomings and also examines stakeholders’ viewpoint of project quality in order to promote the improvement of outcomes throughout a project’s lifecycle. It proposes a set of arranged information as a basis for development of prospective framework which ultimately aims to improve project quality outcomes. The subsequent framework that will be developed from this research will provide project managers and owners with the required information and strategic direction to achieve their own and their stakeholders’ targets for implementation of quality practices and achievement of high quality outcomes on their future projects.

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The assumption that mesenchymal stromal cell (MSC)-based therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo significant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading. Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5’-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identified as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration. These results suggest that MSC migration is controlled by CD73 CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfil their regenerative functions.

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In an Australian context, the term hooning refers to risky driving behaviours such as illegal street racing and speed trials, as well as behaviours that involve unnecessary noise and smoke, which include burn outs, donuts, fish tails, drifting and other skids. Hooning receives considerable negative media attention in Australia, and since the 1990s all Australian jurisdictions have implemented vehicle impoundment programs to deal with the problem. However, there is limited objective evidence of the road safety risk associated with hooning behaviours. Attempts to estimate the risk associated with hooning are limited by official data collection and storage practices, and the willingness of drivers to admit to their illegal behaviour in the event of a crash. International evidence suggests that illegal street racing is associated with only a small proportion of fatal crashes; however, hooning in an Australian context encompasses a broader group of driving behaviours than illegal street racing alone, and it is possible that the road safety risks will differ with these behaviours. There is evidence from North American jurisdictions that vehicle impoundment programs are effective for managing drink driving offenders, and drivers who continue to drive while disqualified or suspended both during and post-impoundment. However, these programs used impoundment periods of 30 – 180 days (depending on the number of previous offences). In Queensland the penalty for a first hooning offence is 48 hours, while the vehicle can be impounded for up to 3 months for a second offence, or permanently for a third or subsequent offence within three years. Thus, it remains unclear whether similar effects will be seen for hooning offenders in Australia, as no evaluations of vehicle impoundment programs for hooning have been published. To address these research needs, this program of research consisted of three complementary studies designed to: (1) investigate the road safety implications of hooning behaviours in terms of the risks associated with the specific behaviours, and the drivers who engage in these behaviours; and (2) assess the effectiveness of current approaches to dealing with the problem; in order to (3) inform policy and practice in the area of hooning behaviour. Study 1 involved qualitative (N = 22) and quantitative (N = 290) research with drivers who admitted engaging in hooning behaviours on Queensland roads. Study 2 involved a systematic profile of a large sample of drivers (N = 834) detected and punished for a hooning offence in Queensland, and a comparison of their driving and crash histories with a randomly sampled group of Queensland drivers with the same gender and age distribution. Study 3 examined the post-impoundment driving behaviour of hooning offenders (N = 610) to examine the effects of vehicle impoundment on driving behaviour. The theoretical framework used to guide the research incorporated expanded deterrence theory, social learning theory, and driver thrill-seeking perspectives. This framework was used to explore factors contributing to hooning behaviours, and interpret the results of the aspects of the research designed to explore the effectiveness of vehicle impoundment as a countermeasure for hooning. Variables from each of the perspectives were related to hooning measures, highlighting the complexity of the behaviour. This research found that the road safety risk of hooning behaviours appears low, as only a small proportion of the hooning offences in Study 2 resulted in a crash. However, Study 1 found that hooning-related crashes are less likely to be reported than general crashes, particularly when they do not involve an injury, and that higher frequencies of hooning behaviours are associated with hooning-related crash involvement. Further, approximately one fifth of drivers in Study 1 reported being involved in a hooning-related crash in the previous three years, which is comparable to general crash involvement among the general population of drivers in Queensland. Given that hooning-related crashes represented only a sub-set of crash involvement for this sample, this suggests that there are risks associated with hooning behaviour that are not apparent in official data sources. Further, the main evidence of risk associated with the behaviour appears to relate to the hooning driver, as Study 2 found that these drivers are likely to engage in other risky driving behaviours (particularly speeding and driving vehicles with defects or illegal modifications), and have significantly more traffic infringements, licence sanctions and crashes than drivers of a similar (i.e., young) age. Self-report data from the Study 1 samples indicated that Queensland’s vehicle impoundment and forfeiture laws are perceived as severe, and that many drivers have reduced their hooning behaviour to avoid detection. However, it appears that it is more common for drivers to have simply changed the location of their hooning behaviour to avoid detection. When the post-impoundment driving behaviour of the sample of hooning offenders was compared to their pre-impoundment behaviour to examine the effectiveness of vehicle impoundment in Study 3, it was found that there was a small but significant reduction in hooning offences, and also for other traffic infringements generally. As Study 3 was observational, it was not possible to control for extraneous variables, and is, therefore, possible that some of this reduction was due to other factors, such as a reduction in driving exposure, the effects of changes to Queensland’s Graduated Driver Licensing scheme that were implemented during the study period and affected many drivers in the offender sample due to their age, or the extension of vehicle impoundment to other types of offences in Queensland during the post-impoundment period. However, there was a protective effect observed, in that hooning offenders did not show the increase in traffic infringements in the post period that occurred within the comparison sample. This suggests that there may be some effect of vehicle impoundment on the driving behaviour of hooning offenders, and that this effect is not limited to their hooning driving behaviour. To be more confident in these results, it is necessary to measure driving exposure during the post periods to control for issues such as offenders being denied access to vehicles. While it was not the primary aim of this program of research to compare the utility of different theoretical perspectives, the findings of the research have a number of theoretical implications. For example, it was found that only some of the deterrence variables were related to hooning behaviours, and sometimes in the opposite direction to predictions. Further, social learning theory variables had stronger associations with hooning. These results suggest that a purely legal approach to understanding hooning behaviours, and designing and implementing countermeasures designed to reduce these behaviours, are unlikely to be successful. This research also had implications for policy and practice, and a number of recommendations were made throughout the thesis to improve the quality of relevant data collection practices. Some of these changes have already occurred since the expansion of the application of vehicle impoundment programs to other offences in Queensland. It was also recommended that the operational and resource costs of these laws should be compared to the road safety benefits in ongoing evaluations of effectiveness to ensure that finite traffic policing resources are allocated in a way that produces maximum road safety benefits. However, as the evidence of risk associated with the hooning driver is more compelling than that associated with hooning behaviour, it was argued that the hooning driver may represent the better target for intervention. Suggestions for future research include ongoing evaluations of the effectiveness of vehicle impoundment programs for hooning and other high-risk driving behaviours, and the exploration of additional potential targets for intervention to reduce hooning behaviour. As the body of knowledge regarding the factors contributing to hooning increases, along with the identification of potential barriers to the effectiveness of current countermeasures, recommendations for changes in policy and practice for hooning behaviours can be made.

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In a similar fashion to many western countries, the political context of Japan has been transformed since the 1975 UN World Conference on Women, which eventually led to the establishment of the Basic Law for a Gender-equal Society in Japan in 1999. The Basic Law sets out a series of general guidelines across every field of society, including education. This trajectory policy research study targets gender issues in Japanese higher education and follows the development of the Basic Law and, in particular, how it has been interpreted by bureaucrats and implemented within the field of higher education. This feminist policy research study examines Japanese power relationships within the field of gender and identifies gender discourses embedded within Japanese gender equity policy documents. The study documents the experiences of, and strategies used by, Japanese feminists in relation to gender equity policies in education. Drawing on critical feminist theory and feminist critical discourse theory, the study explores the relationship between gender discourses and social practices and analyses how unequal gender relations have been sustained through the implementation of Japanese gender equity policy. Feminist critical policy analysis and feminist critical discourse analysis have been used to examine data collected through interviews with key players, including policy makers and policy administrators from the national government and higher education institutions offering teacher education courses. The study also scrutinises the minutes of government meetings, and other relevant policy documents. The study highlights the struggles between policy makers in the government and bureaucracy, and feminist educators working for change. Following an anti-feminist backlash, feminist discourses in the original policy documents were weakened or marginalised in revisions, ultimately weakening the impact of the Basic Law in the higher education institutions. The following four key findings are presented within the research: 1) tracking of the original feminist teachers’ movement that existed just prior to the development of the Basic Law in 1999; 2) the formation of the Basic Law, and how the policy resulted in a weakening of the main tenets of women’s policy from a feminist perspective; 3) the problematic manner in which the Basic Law was interpreted at the bureaucratic level; and 4) the limited impact of the Basic Law on higher education and the strategies and struggles of feminist scholars in reaction to this law.

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The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g., sleeve gastrectomy and Roux en-Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise-induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying which we hypothesise will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g., diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.

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This paper discusses the counterproductive behaviour of ‘workplace mobbing’ where gossip, rumour, innuendo, and malicious accusations are reported to unfairly target and discredit targeted workers. The discussion is based on an Australian study of reports from public sector employees who self identified as targets of workplace mobbing. The behaviours are typically covert and are sometimes instigated and perpetuated by management. In focusing on three themes that emerged from the interview study, the paper discusses the sometimes toxic nature of public sector culture, mobbing behaviours and workplace expulsion. It also discusses some recommended regulatory and organizational responses that could potentially reduce the occurrence of such behaviours.

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This paper introduces the concept of workplace mobbing as a destructive organizational behaviour of psychological assaults perpetrated against the target causing them harm and loss of employment. The discussion is drawn from a three year Australian study of 212 self identified targets of workplace mobbing behaviours. The behaviours are typically covert with informal networks and friendship loyalties providing effective mechanisms for emotional abuse, including those arising from human resource management practices. This paper discusses the manipulation of informal sources of power, with the use of gossip, rumour, hearsay, and innuendo to discredit and demonise those targeted. The study explores some of the systemic reasons for these behaviours and identifies some of the contributing risk factors and suggests management practices that can minimise the harm caused.

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A forced landing is an unscheduled event in flight requiring an emergency landing, and is most commonly attributed to engine failure, failure of avionics or adverse weather. Since the ability to conduct a successful forced landing is the primary indicator for safety in the aviation industry, automating this capability for unmanned aerial vehicles (UAVs) will help facilitate their integration into, and subsequent routine operations over civilian airspace. Currently, there is no commercial system available to perform this task; however, a team at the Australian Research Centre for Aerospace Automation (ARCAA) is working towards developing such an automated forced landing system. This system, codenamed Flight Guardian, will operate onboard the aircraft and use machine vision for site identification, artificial intelligence for data assessment and evaluation, and path planning, guidance and control techniques to actualize the landing. This thesis focuses on research specific to the third category, and presents the design, testing and evaluation of a Trajectory Generation and Guidance System (TGGS) that navigates the aircraft to land at a chosen site, following an engine failure. Firstly, two algorithms are developed that adapts manned aircraft forced landing techniques to suit the UAV planning problem. Algorithm 1 allows the UAV to select a route (from a library) based on a fixed glide range and the ambient wind conditions, while Algorithm 2 uses a series of adjustable waypoints to cater for changing winds. A comparison of both algorithms in over 200 simulated forced landings found that using Algorithm 2, twice as many landings were within the designated area, with an average lateral miss distance of 200 m at the aimpoint. These results present a baseline for further refinements to the planning algorithms. A significant contribution is seen in the design of the 3-D Dubins Curves planning algorithm, which extends the elementary concepts underlying 2-D Dubins paths to account for powerless flight in three dimensions. This has also resulted in the development of new methods in testing for path traversability, in losing excess altitude, and in the actual path formation to ensure aircraft stability. Simulations using this algorithm have demonstrated lateral and vertical miss distances of under 20 m at the approach point, in wind speeds of up to 9 m/s. This is greater than a tenfold improvement on Algorithm 2 and emulates the performance of manned, powered aircraft. The lateral guidance algorithm originally developed by Park, Deyst, and How (2007) is enhanced to include wind information in the guidance logic. A simple assumption is also made that reduces the complexity of the algorithm in following a circular path, yet without sacrificing performance. Finally, a specific method of supplying the correct turning direction is also used. Simulations have shown that this new algorithm, named the Enhanced Nonlinear Guidance (ENG) algorithm, performs much better in changing winds, with cross-track errors at the approach point within 2 m, compared to over 10 m using Park's algorithm. A fourth contribution is made in designing the Flight Path Following Guidance (FPFG) algorithm, which uses path angle calculations and the MacCready theory to determine the optimal speed to fly in winds. This algorithm also uses proportional integral- derivative (PID) gain schedules to finely tune the tracking accuracies, and has demonstrated in simulation vertical miss distances of under 2 m in changing winds. A fifth contribution is made in designing the Modified Proportional Navigation (MPN) algorithm, which uses principles from proportional navigation and the ENG algorithm, as well as methods specifically its own, to calculate the required pitch to fly. This algorithm is robust to wind changes, and is easily adaptable to any aircraft type. Tracking accuracies obtained with this algorithm are also comparable to those obtained using the FPFG algorithm. For all three preceding guidance algorithms, a novel method utilising the geometric and time relationship between aircraft and path is also employed to ensure that the aircraft is still able to track the desired path to completion in strong winds, while remaining stabilised. Finally, a derived contribution is made in modifying the 3-D Dubins Curves algorithm to suit helicopter flight dynamics. This modification allows a helicopter to autonomously track both stationary and moving targets in flight, and is highly advantageous for applications such as traffic surveillance, police pursuit, security or payload delivery. Each of these achievements serves to enhance the on-board autonomy and safety of a UAV, which in turn will help facilitate the integration of UAVs into civilian airspace for a wider appreciation of the good that they can provide. The automated UAV forced landing planning and guidance strategies presented in this thesis will allow the progression of this technology from the design and developmental stages, through to a prototype system that can demonstrate its effectiveness to the UAV research and operations community.

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The reduction of CO2 emissions and social exclusion are two key elements of UK transport strategy. Despite intensive research on each theme, little effort has so far been made linking the relationship between emissions and social exclusion. In addition, current knowledge on each theme is limited to urban areas; little research is available on these themes for rural areas. This research contributes to this gap in the literature by analysing 157 weekly activity-travel diary data collected from three case study areas with differential levels of area accessibility and area mobility options, located in rural Northern Ireland. Individual weekly CO2 emission levels from personal travel diaries (both hot exhaust emission and cold-start emission) were calculated using average speed models for different modes of transport. The socio-spatial patterns associated with CO2 emissions were identified using a general linear model whereas binary logistic regression analyses were conducted to identify mode choice behaviour and activity patterns. This research found groups that emitted a significantly lower level of CO2 included individuals living in an area with a higher level of accessibility and mobility, non-car, non-working, and low-income older people. However, evidence in this research also shows that although certain groups (e.g. those working, and residing in an area with a lower level of accessibility) emitted higher levels of CO2, their rate of participation in activities was however found to be significantly lower compared to their counterparts. Based on the study findings, this research highlights the need for both soft (e.g. teleworking) and physical (e.g. accessibility planning) policy measures in rural areas in order to meet government’s stated CO2 reduction targets while at the same time enhancing social inclusion.