An impression of home: player nostalgia and the impulse to explore game worlds

This is the accepted version of the paper following peer review.

„Moja osobista przestrzeń” – prywatne wirtualne kolekcje sztuki

The phenomenon analyzed in the essay My Personal Space – The Private Virtual Collections of Art is the possibility of visiting the world’s museums by means of the Internet – visiting indirect, nevertheless enabling peaceful, profound, multiple and free contemplation of art. The function of Mon espace personnel (My Personal Space) of French museums of Louvre and Orsay that reveals some radical modifications in the perception, understanding and reception of art, is an illustration of this phenomenon. Using Mon espace personnel means traversing the virtual Louvre or Orsay and choosing works of art, their descriptions, analyses, publications etc. and then adding them to the internaut’s personal thematic albums. The phenomenon described is a starting point to the reflection on the significance of the space in which art exists (called, according to Golka, the form of art’s presence) with its ontology as well as its functions and the character of its reception. The identification of what this space is, in the context of the hybridization of the form and the content and the emergence of the computer culture (Manovich) as well as in the context of the popularization of the reality (Krajewski) and the decentralization of the world of art (Wójtowicz), is an important part of this essay. These phenomena are also inscribed in a wider context of the changes of the character, mission and role of the museum in the time of the digital revolution.

Rationing Antiretroviral Therapy for HIV/AIDS in Africa: Efficiency, Equity, and Reality

Background: Rationing of access to antiretroviral therapy already exists in sub-Saharan Africa and will intensify as national treatment programs develop. The number of people who are medically eligible for therapy will far exceed the human, infrastructural, and financial resources available, making rationing of public treatment services inevitable. Methods: We identified 15 criteria by which antiretroviral therapy could be rationed in African countries and analyzed the resulting rationing systems across 5 domains: clinical effectiveness, implementation feasibility, cost, economic efficiency, and social equity. Findings: Rationing can be explicit or implicit. Access to treatment can be explicitly targeted to priority subpopulations such as mothers of newborns, skilled workers, students, or poor people. Explicit conditions can also be set that cause differential access, such as residence in a designated geographic area, co-payment, access to testing, or a demonstrated commitment to adhere to therapy. Implicit rationing on the basis of first-come, first-served or queuing will arise when no explicit system is enforced; implicit systems almost always allow a high degree of queue-jumping by the elite. There is a direct tradeoff between economic efficiency and social equity. Interpretation: Rationing is inevitable in most countries for some period of time. Without deliberate social policy decisions, implicit rationing systems that are neither efficient nor equitable will prevail. Governments that make deliberate choices, and then explain and defend those choices to their constituencies, are more likely to achieve a socially desirable outcome from the large investments now being made than are those that allow queuing and queue-jumping to dominate.

Treatment of HIV/AIDS at South Africa's Largest Employers: Myth and Reality

Background: In the past three years, many large employers in South Africa have announced publicly their intention of making antiretroviral treatment (ART) available to employees. Reports of the scope and success of these programs have been mostly anecdotal. This study surveyed the largest private sector employers in South Africa to determine the proportion of employees with access to ART through employer-sponsored HIV/AIDS treatment programs. Methods: All 64 private sector and parastatal employers in South Africa with more than 6,000 employees were identified and contacted. Those that agreed to participate were interviewed by telephone using a structured questionnaire. Results: 52 companies agreed to participate. Among these companies, 63% of employees had access to employer-sponsored care and treatment for HIV/AIDS. Access varied widely by sector, however. Approximately 27% of suspected HIV-positive employees were enrolled in HIV/AIDS disease management programs, or 4.4% of the workforce overall. Fewer than 4,000 employees in the entire sample were receiving antiretroviral therapy. In-house (employer) disease management programs and independent disease management programs achieved higher uptake of services than did medical aid schemes. Conclusions: Publicity by large employers about their treatment programs should be interpreted cautiously. While there is a high level of access to treatment, uptake of services is low and only a small fraction of employees medically eligible for antiretroviral therapy are receiving it.

Effectiveness of Loss labeling in Improving TCP Performance in Wired/Wireless Networks

The current congestion-oriented design of TCP hinders its ability to perform well in hybrid wireless/wired networks. We propose a new improvement on TCP NewReno (NewReno-FF) using a new loss labeling technique to discriminate wireless from congestion losses. The proposed technique is based on the estimation of average and variance of the round trip time using a filter cal led Flip Flop filter that is augmented with history information. We show the comparative performance of TCP NewReno, NewReno-FF, and TCP Westwood through extensive simulations. We study the fundamental gains and limits using TCP NewReno with varying Loss Labeling accuracy (NewReno-LL) as a benchmark. Lastly our investigation opens up important research directions. First, there is a need for a finer grained classification of losses (even within congestion and wireless losses) for TCP in heterogeneous networks. Second, it is essential to develop an appropriate control strategy for recovery after the correct classification of a packet loss.

The CLARITY modular ambient health and wellness measurement platform

Emerging healthcare applications can benefit enormously from recent advances in pervasive technology and computing. This paper introduces the CLARITY Modular Ambient Health and Wellness Measurement Platform:, which is a heterogeneous and robust pervasive healthcare solution currently under development at the CLARITY Center for Sensor Web Technologies. This intelligent and context-aware platform comprises the Tyndall Wireless Sensor Network prototyping system, augmented with an agent-based middleware and frontend computing architecture. The key contribution of this work is to highlight how interoperability, expandability, reusability and robustness can be manifested in the modular design of the constituent nodes and the inherently distributed nature of the controlling software architecture.Emerging healthcare applications can benefit enormously from recent advances in pervasive technology and computing. This paper introduces the CLARITY Modular Ambient Health and Wellness Measurement Platform:, which is a heterogeneous and robust pervasive healthcare solution currently under development at the CLARITY Center for Sensor Web Technologies. This intelligent and context-aware platform comprises the Tyndall Wireless Sensor Network prototyping system, augmented with an agent-based middleware and frontend computing architecture. The key contribution of this work is to highlight how interoperability, expandability, reusability and robustness can be manifested in the modular design of the constituent nodes and the inherently distributed nature of the controlling software architecture.

An investigation of innovation and knowledge creation in virtual worlds

The Internet and World Wide Web have had, and continue to have, an incredible impact on our civilization. These technologies have radically influenced the way that society is organised and the manner in which people around the world communicate and interact. The structure and function of individual, social, organisational, economic and political life begin to resemble the digital network architectures upon which they are increasingly reliant. It is increasingly difficult to imagine how our ‘offline’ world would look or function without the ‘online’ world; it is becoming less meaningful to distinguish between the ‘actual’ and the ‘virtual’. Thus, the major architectural project of the twenty-first century is to “imagine, build, and enhance an interactive and ever changing cyberspace” (Lévy, 1997, p. 10). Virtual worlds are at the forefront of this evolving digital landscape. Virtual worlds have “critical implications for business, education, social sciences, and our society at large” (Messinger et al., 2009, p. 204). This study focuses on the possibilities of virtual worlds in terms of communication, collaboration, innovation and creativity. The concept of knowledge creation is at the core of this research. The study shows that scholars increasingly recognise that knowledge creation, as a socially enacted process, goes to the very heart of innovation. However, efforts to build upon these insights have struggled to escape the influence of the information processing paradigm of old and have failed to move beyond the persistent but problematic conceptualisation of knowledge creation in terms of tacit and explicit knowledge. Based on these insights, the study leverages extant research to develop the conceptual apparatus necessary to carry out an investigation of innovation and knowledge creation in virtual worlds. The study derives and articulates a set of definitions (of virtual worlds, innovation, knowledge and knowledge creation) to guide research. The study also leverages a number of extant theories in order to develop a preliminary framework to model knowledge creation in virtual worlds. Using a combination of participant observation and six case studies of innovative educational projects in Second Life, the study yields a range of insights into the process of knowledge creation in virtual worlds and into the factors that affect it. The study’s contributions to theory are expressed as a series of propositions and findings and are represented as a revised and empirically grounded theoretical framework of knowledge creation in virtual worlds. These findings highlight the importance of prior related knowledge and intrinsic motivation in terms of shaping and stimulating knowledge creation in virtual worlds. At the same time, they highlight the importance of meta-knowledge (knowledge about knowledge) in terms of guiding the knowledge creation process whilst revealing the diversity of behavioural approaches actually used to create knowledge in virtual worlds and. This theoretical framework is itself one of the chief contributions of the study and the analysis explores how it can be used to guide further research in virtual worlds and on knowledge creation. The study’s contributions to practice are presented as actionable guide to simulate knowledge creation in virtual worlds. This guide utilises a theoretically based classification of four knowledge-creator archetypes (the sage, the lore master, the artisan, and the apprentice) and derives an actionable set of behavioural prescriptions for each archetype. The study concludes with a discussion of the study’s implications in terms of future research.

P-glycoprotein inhibition as a strategy to increase drug delivery across the blood-brain barrier: focus on antidepressants

Depression is among the leading causes of disability worldwide. Currently available antidepressant drugs have unsatisfactory efficacy, with up to 60% of depressed patients failing to respond adequately to treatment. Emerging evidence has highlighted a potential role for the efflux transporter P-glycoprotein (P-gp), expressed at the blood-brain barrier (BBB), in the aetiology of treatment-resistant depression. In this thesis, the potential of P-gp inhibition as a strategy to enhance the brain distribution and pharmacodynamic effects of antidepressant drugs was investigated. Pharmacokinetic studies demonstrated that administration of the P-gp inhibitors verapamil or cyclosporin A (CsA) enhanced the BBB transport of the antidepressants imipramine and escitalopram in vivo. Furthermore, both imipramine and escitalopram were identified as transported substrates of human P-gp in vitro. Contrastingly, human P-gp exerted no effect on the transport of four other antidepressants (amitriptyline, duloxetine, fluoxetine and mirtazapine) in vitro. Pharmacodynamic studies revealed that pre-treatment with verapamil augmented the behavioural effects of escitalopram in the tail suspension test (TST) of antidepressant-like activity in mice. Moreover, pre-treatment with CsA exacerbated the behavioural manifestation of an escitalopram-induced mouse model of serotonin syndrome, a serious adverse reaction associated with serotonergic drugs. This finding highlights the potential for unwanted side-effects which may occur due to increasing brain levels of antidepressants by P-gp inhibition, although further studies are needed to fully elucidate the mechanism(s) at play. Taken together, the research outlined in this thesis indicates that P-gp may restrict brain concentrations of escitalopram and imipramine in patients. Moreover, we show that increasing the brain distribution of an antidepressant by P-gp inhibition can result in an augmentation of antidepressant-like activity in vivo. These findings raise the possibility that P-gp inhibition may represent a potentially beneficial strategy to augment antidepressant treatment in clinical practice. Further studies are now warranted to evaluate the safety and efficacy of this approach.

The quality of deliberation in Northern Ireland's district policing partnerships

This study uses theoretical based deliberative democratic dimensions to measure the deliberative quality of Northern Ireland’s District Policing Partnership (DPP) meetings in public. The study combines Habermasian, and Young’s deliberative concepts to create an Augmented Discourse Quality Index. This Augmented DQI is employed by this research as am empirical instrument to establish the true deliberative nature of these DPP meetings in public. The overall goal of this study is two-fold. First; to gain an in-depth understanding of Northern Ireland’s DPPs in relation to deliberative democratic theory, specifically regarding how these policing/public partnerships stand up under a deliberative democratic lens. The second goal is to provide a possible framework by which deliberative quality can be more accurately measured. In that frameworks which are designed to measure deliberative quality should include not only the dimensions for rational participation, but also include broader terms of communication such as greeting, rhetoric and story-telling.

Between the worlds: otherworld women as intermediaries in early Irish literature

This thesis examines the ways in which Otherworldly women acted as intermediaries between the Otherworld and mortal world in early Irish literature. First it establishes the position of women in early Ireland so that appropriate comparisons can be made between mortal and Otherworld women throughout the thesis. Also, it defines what is meant by the ‘Otherworld’ and its relevence to the early Irish. It then goes on to discuss the differing goals of various intermediaries in early Irish texts, and in what manner they interact with mortals. It briefly looks at how Otherworld male intermediaries are treated differently in the literature, and why early authors might have used women in these roles as often as they did.

Towards enhanced divine-human-earth relations: a Christian-Buddhist contribution

The central claim of the dissertation is that lesser known and somewhat neglected, yet influential thinkers, within classical religious traditions have something worthwhile to contribute to the kind of ethos we should adopt in the face of the world’s various environmental crises. Moreover an exploration of such perspectives is best done in dialogue, particularly between Eastern and Western thought. I examine this claim primarily through a dialogue between the Christian philosopher John Scottus Eriugena and the Japanese Buddhist philosopher Kūkai (Kōbō Daishi). This dialogue, framed by the triad of divine-human-earth relations, primarily emphasises the oneness of all reality, and it finds expression in Eriugena’s concept of natura or phusis and Kūkai’s central teaching that the phenomenal world is the cosmic Buddha Dainichi. By highlighting this focus, I contribute to the existing academic field of ecology and religion on the subject of holism. However, I go beyond the materialist focus that generally marks such ecological holism within that field, offering instead a more metaphysical approach. This is indicated through my use of the concept of ‘immanental transcendence’ to describe Eriugena’s and Kūkai’s dynamic, numinous and mysterious notion of reality, as well as my exploration of Eriugena’s concept of theophany and Kūkai’s notion of kaji. I further explore how both philosophers highlight the human role in the process of reaching enlightenment—understood as attaining union with the whole. In that regard, I note significant differences in their positions: in particular, I note that Kūkai’s emphasis on bodily practices contrasts with Eriugena’s more conceptual approach. Finally to bolster my claim, I examine some ecologically oriented understandings of contemporary phenomenological approaches found particularly in the work of Jean-Luc Marion and to a lesser extent Merleau-Ponty, arguing that these reflect notions of reality and of the human role similar to those of the medieval philosophers.

The multiple reality: A critical study on Alfred Schutz’s sociology of the finite provinces of meaning

This work is a critical introduction to Alfred Schutz’s sociology of the multiple reality and an enterprise that seeks to reassess and reconstruct the Schutzian project. In the first part of the study, I inquire into Schutz’s biographical context that surrounds the germination of this conception and I analyse the main texts of Schutz where he has dealt directly with ‘finite provinces of meaning.’ On the basis of this analysis, I suggest and discuss, in Part II, several solutions to the shortcomings of the theoretical system that Schutz drew upon the sociological problem of multiple reality. Specifically, I discuss problems related to the structure, the dynamics, and the interrelationing of finite provinces of meaning as well as the way they relate to the questions of narrativity, experience, space, time, and identity.

Characterisation of the role of Fas in intestinal inflammation and cancer

Background: The role of Fas (CD95) and its ligand, Fas ligand (FasL/CD95L), is poorly understood in the intestine. Whilst Fas is best studies in terms of its function in apoptosis, recent studies suggest that Fas ligation may mediate additional, non-apoptotic functions such as inflammation. Toll like Receptors (TLRs) play an important role in mediating inflammation and homeostasis in the intestine. Recent studies have shown that a level of crosstalk exists between the Fas and TLR signalling pathways but this has not yet been investigated in the intestine. Aim: The aim of this study was to evaluate potential cross-talk between TLRs and Fas/FasL system in intestinal cancer cells. Results: Treatment with TLR4 and TLR5 ligands, but not ligands for TLR2 and TLR9 increased the expression of Fas and FasL in intestinal cancer cells in vitro. Consistent with this, expression of Fas and FasL was reduced in the distal colon tissue from germ-free (GF), TLR4 and TLR5 knock-out (KO) mice but was unchanged in TLR2KO tissue, suggesting that intestinal cancer cells display a degree of specificity in their ability to upregulate Fas and FasL expression in response to TLR ligation. Expression of both Fas and FasL was significantly reduced in TRIF KO tissue, indicating that signalling via TRIF by TLR4 and TLR5 agonists may be responsible for the induction of Fas and FasL expression in intestinal cancer cells. In addition, modulating Fas signalling using agonistic anti-Fas augmented TLR4 and TLR5-mediated tumour necrosis factor alpha (TNFα) and interleukin 8 (IL)-8 production by intestinal cancer cells, suggesting crosstalk occurs between these receptors in these cells. Furthermore, suppression of Fas in intestinal cancer cells reduced the ability of the intestinal pathogens, Salmonella typhimurium and Listeria monocytogenes to induce the expression of IL-8, suggesting that Fas signalling may play a role in intestinal host defence against pathogens. Inflammation is known to be important in colon tumourigenesis and Fas signalling on intestinal cancer cells has been shown to result in the production of inflammatory mediators. Fas-mediated signalling may therefore play a role in colon cancer development. Suppression of tumour-derived Fas by 85% led to a reduction in the tumour volume and changes in tumour infiltrating macrophages and neutrophils. TLR4 signalling has been shown to play a role in colon cancer via the recruitment and activation of alternatively activated immune cells. Given the crosstalk seen between Fas and TLR4 signalling in intestinal cancer cells in vitro, suppressing Fas signalling may enhance the efficacy of TLR4 antagonism in vivo. TLR4 antagonism resulted in smaller tumours with fewer infiltrating neutrophils. Whilst Fas downregulation did not significantly augment the ability of TLR4 antagonism to reduce the final tumour volume, Fas suppression may augment the anti-tumour effects of TLR4 antagonism as neutrophil infiltration was further reduced upon combinatorial treatment. Conclusion: Together, this study demonstrates evidence of a new role for Fas in the intestinal immune response and that manipulating Fas signalling has potential anti-tumour benefit.

Investigating the role of Fas (CD95) signalling in the modification of innate immune induced inflammation

Background/Aim: It has been demonstrated that a number of pathologies occur as a result of dysregulation of the immune system. Whilst classically associated with apoptosis, the Fas (CD95) signalling pathway plays a role in inflammation. Studies have demonstrated that Fas activation augments TLR4-mediated MyD88-dependent cytokine production. Studies have also shown that the Fas adapter protein FADD is required for RIG-I-induced IFNβ production. As a similar signalling pathway exists between RIG-I, TLR3 and the MyD88- independent of TLR4, we hypothesised that Fas activation may modulate both TLR3- and TLR4-induced cytokine production. Results: Fas activation reduced poly I:C-induced IFNβ, IL-8, IL-10 and TNFα production whilst augmenting poly I:C-, poly A:U- and Sendai virus-induced IP-10 production. TLR3-, RIG-I- and MDA5-induced IP-10 luciferase activation were inhibited by the Fas adapter protein FADD using overexpression studies. Poly I:C-induced phosphorylation of p-38 and JNK MAPK were reduced by Fas activation. Overexpression of FADD induced AP-1 luciferase activation. Point mutations in the AP-1 binding site enhanced poly I:C-induced IP- 10 production. LPS-induced IL-10, IL-12, IL-8 and TNFα production were enhanced by Fas activation, whilst reducing LPS-induced IFNβ production. Absence of FADD using FADD-/- MEFs resulted in impaired IFNβ production. Overexpression studies using FADD augmented TLR4-, MyD88- and TRIF-induced IFNβ luciferase activation. Overexpression studies also suggested that enhanced TLR4-induced IFNβ production was independent of NFκB activation. Conclusion: Viral-induced IP-10 production is augmented by Fas activation by reducing the phosphorylation of p-38 and JNK MAPKs, modulating AP-1 activation. The Fas adapterprotein FADD is required for TLR4-induced IFNβ production. Studies presented here demonstrate that the Fas signalling pathway can therefore modulate the immune response. Our data demonstrates that this modulatory effect is mediated by its adapter protein FADD, tailoring the immune response by acting as a molecular switch. This ensures the appropriate immune response is mounted, thus preventing an exacerbated immune response.

Polymorphisms in the ACE and ADRB2 genes and risks of aging-associated phenotypes: the case of myocardial infarction.

Multiple functions of the beta2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) genes warrant studies of their associations with aging-related phenotypes. We focus on multimarker analyses and analyses of the effects of compound genotypes of two polymorphisms in the ADRB2 gene, rs1042713 and rs1042714, and 11 polymorphisms of the ACE gene, on the risk of such an aging-associated phenotype as myocardial infarction (MI). We used the data from a genotyped sample of the Framingham Heart Study Offspring (FHSO) cohort (n = 1500) followed for about 36 years with six examinations. The ADRB2 rs1042714 (C-->G) polymorphism and two moderately correlated (r(2) = 0.77) ACE polymorphisms, rs4363 (A-->G) and rs12449782 (A-->G), were significantly associated with risks of MI in this aging cohort in multimarker models. Predominantly linked ACE genotypes exhibited opposite effects on MI risks, e.g., the AA (rs12449782) genotype had a detrimental effect, whereas the predominantly linked AA (rs4363) genotype exhibited a protective effect. This trade-off occurs as a result of the opposite effects of rare compound genotypes of the ACE polymorphisms with a single dose of the AG heterozygote. This genetic trade-off is further augmented by the selective modulating effect of the rs1042714 ADRB2 polymorphism. The associations were not altered by adjustment for common MI risk factors. The results suggest that effects of single specific genetic variants of the ADRB2 and ACE genes on MI can be readily altered by gene-gene or/and gene-environmental interactions, especially in large heterogeneous samples. Multimarker genetic analyses should benefit studies of complex aging-associated phenotypes.