Functional evaluation of genetic variants associated with endometriosis near GREB1

STUDY QUESTION: Do DNA variants in the growth regulation by estrogen in breast cancer 1 (GREB1) region regulate endometrial GREB1 expression and increase the risk of developing endometriosis in women? SUMMARY ANSWER: We identified new single nucleotide polymorphisms (SNPs) with strong association with endometriosis at the GREB1 locus although we did not detect altered GREB1 expression in endometriosis patients with defined genotypes. WHAT IS ALREADY KNOWN: Genome-wide association studies have identified the GREB1 region on chromosome 2p25.1 for increasing endometriosis risk. The differential expression of GREB1 has also been reported by others in association with endometriosis disease phenotype. STUDY DESIGN, SIZE, DURATION: Fine mapping studies comprehensively evaluated SNPs within the GREB1 region in a large-scale data set (>2500 cases and >4000 controls). Publicly available bioinformatics tools were employed to functionally annotate SNPs showing the strongest association signal with endometriosis risk. Endometrial GREB1 mRNA and protein expression was studied with respect to phases of the menstrual cycle (n = 2-45 per cycle stage) and expression quantitative trait loci (eQTL) analysis for significant SNPs were undertaken for GREB1 [mRNA (n = 94) and protein (n = 44) in endometrium]. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants in this study are females who provided blood and/or endometrial tissue samples in a hospital setting. The key SNPs were genotyped using Sequenom MassARRAY. The functional roles and regulatory annotations for identified SNPs are predicted by various publicly available bioinformatics tools. Endometrial GREB1 expression work employed qRT-PCR, western blotting and immunohistochemistry studies. MAIN RESULTS AND THE ROLE OF CHANCE: Fine mapping results identified a number of SNPs showing stronger association (0.004 < P < 0.032) with endometriosis risk than the original GWAS SNP (rs13394619) (P = 0.034). Some of these SNPs were predicted to have functional roles, for example, interaction with transcription factor motifs. The haplotype (a combination of alleles) formed by the risk alleles from two common SNPs showed significant association (P = 0.026) with endometriosis and epistasis analysis showed no evidence for interaction between the two SNPs, suggesting an additive effect of SNPs on endometriosis risk. In normal human endometrium, GREB1 protein expression was altered depending on the cycle stage (significantly different in late proliferative versus late secretory, P < 0.05) and cell type (glandular epithelium, not stromal cells). However, GREB1 expression in endometriosis cases versus controls and eQTL analyses did not reveal any significant changes. LIMITATIONS, REASONS FOR CAUTION: In silico prediction tools are generally based on cell lines different to our tissue and disease of interest. Functional annotations drawn from these analyses should be considered with this limitation in mind. We identified cell-specific and hormone-specific changes in GREB1 protein expression. The lack of a significant difference observed following our GREB1 expression studies may be the result of moderate power on mixed cell populations in the endometrial tissue samples. WIDER IMPLICATIONS OF THE FINDINGS: This study further implicates the GREB1 region on chromosome 2p25.1 and the GREB1 gene with involvement in endometriosis risk. More detailed functional studies are required to determine the role of the novel GREB1 transcripts in endometriosis pathophysiology. STUDY FUNDING/COMPETING INTERESTS: Funding for this work was provided by NHMRC Project Grants APP1012245, APP1026033, APP1049472 and APP1046880. There are no competing interests.

No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis

STUDY QUESTION Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk? SUMMARY ANSWER We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN ALREADY The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE OF CHANCE There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk. LIMITATIONS AND REASONS FOR CAUTION The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE FINDINGS The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

What does “futility” mean? An empirical study of doctors’ perceptions

Objective(s) To describe how doctors define and use the terms “futility” and “futile treatment” in end-of-life care. Design, Setting, Participants A qualitative study using semi-structured interviews with 96 doctors across a range of specialties who treat adults at the end of life. Doctors were recruited from three large Australian teaching hospitals and were interviewed from May to July 2013. Results Doctors’ conceptions of futility focused on the quality and chance of patient benefit. Aspects of benefit included physiological effect, weighing benefits and burdens, and quantity and quality of life. Quality and length of life were linked, but many doctors discussed instances when benefit was determined by quality of life alone. Most doctors described the assessment of chance of success in achieving patient benefit as a subjective exercise. Despite a broad conceptual consensus about what futility means, doctors noted variability in how the concept was applied in clinical decision-making. Over half the doctors also identified treatment that is futile but nevertheless justified, such as short-term treatment as part of supporting the family of a dying person. Conclusions There is an overwhelming preference for a qualitative approach to assessing futility, which brings with it variation in clinical decision-making. “Patient benefit” is at the heart of doctors’ definitions of futility. Determining patient benefit requires discussions with patients and families about their values and goals as well as the burdens and benefits of further treatment.

Playing Games on Sets and Models

The most prominent objective of the thesis is the development of the generalized descriptive set theory, as we call it. There, we study the space of all functions from a fixed uncountable cardinal to itself, or to a finite set of size two. These correspond to generalized notions of the universal Baire space (functions from natural numbers to themselves with the product topology) and the Cantor space (functions from natural numbers to the {0,1}-set) respectively. We generalize the notion of Borel sets in three different ways and study the corresponding Borel structures with the aims of generalizing classical theorems of descriptive set theory or providing counter examples. In particular we are interested in equivalence relations on these spaces and their Borel reducibility to each other. The last chapter shows, using game-theoretic techniques, that the order of Borel equivalence relations under Borel reduciblity has very high complexity. The techniques in the above described set theoretical side of the thesis include forcing, general topological notions such as meager sets and combinatorial games of infinite length. By coding uncountable models to functions, we are able to apply the understanding of the generalized descriptive set theory to the model theory of uncountable models. The links between the theorems of model theory (including Shelah's classification theory) and the theorems in pure set theory are provided using game theoretic techniques from Ehrenfeucht-Fraïssé games in model theory to cub-games in set theory. The bottom line of the research declairs that the descriptive (set theoretic) complexity of an isomorphism relation of a first-order definable model class goes in synch with the stability theoretical complexity of the corresponding first-order theory. The first chapter of the thesis has slightly different focus and is purely concerned with a certain modification of the well known Ehrenfeucht-Fraïssé games. There we (me and my supervisor Tapani Hyttinen) answer some natural questions about that game mainly concerning determinacy and its relation to the standard EF-game

Birth of the European individual : Outline of a theory of legal practice

The modern subject is what we can call a self-subjecting individual. This is someone in whose inner reality has been implanted a more permanent governability, a governability that works inside the agent. Michel Foucault s genealogy of the modern subject is the history of its constitution by power practices. By a flight of imagination, suppose that this history is not an evolving social structure or cultural phenomenon, but one of those insects (moth) whose life cycle consists of three stages or moments: crawling larva, encapsulated pupa, and flying adult. Foucault s history of power-practices presents the same kind of miracle of total metamorphosis. The main forces in the general field of power can be apprehended through a generalisation of three rationalities functioning side-by-side in the plurality of different practices of power: domination, normalisation and the law. Domination is a force functioning by the rationality of reason of state: the state s essence is power, power is firm domination over people, and people are the state s resource by which the state s strength is measured. Normalisation is a force that takes hold on people from the inside of society: it imposes society s own reality its empirical verity as a norm on people through silently working jurisdictional operations that exclude pathological individuals too far from the average of the population as a whole. The law is a counterforce to both domination and normalisation. Accounting for elements of legal practice as omnihistorical is not possible without a view of the general field of power. Without this view, and only in terms of the operations and tactical manoeuvres of the practice of law, nothing of the kind can be seen: the only thing that practice manifests is constant change itself. However, the backdrop of law s tacit dimension that is, the power-relations between law, domination and normalisation allows one to see more. In the general field of power, the function of law is exactly to maintain the constant possibility of change. Whereas domination and normalisation would stabilise society, the law makes it move. The European individual has a reality as a problem. What is a problem? A problem is something that allows entry into the field of thought, said Foucault. To be a problem, it is necessary for certain number of factors to have made it uncertain, to have made it lose familiarity, or to have provoked a certain number of difficulties around it . Entering the field of thought through problematisations of the European individual human forms, power and knowledge one is able to glimpse the historical backgrounds of our present being. These were produced, and then again buried, in intersections between practices of power and games of truth. In the problem of the European individual one has suitable circumstances that bring to light forces that have passed through the individual through centuries.

The pursuit-evasion problem of two aircraft in a horizontal plane

The pursuit-evasion problem of two aircraft in a horizontal plane is modelled as a zerosum differential game with capture time as payoff. The aircraft are modelled as point masses with thrust and bank angle controls. The games of kind and degree for this differential game are solved.

Wet and dry spell characteristics of global tropical rainfall

In this study, we analyze satellite-based daily rainfall observations to compare and contrast the wet and dry spell characteristics of tropical rainfall. Defining a wet (dry) spell as the number of consecutive rainy (nonrainy) days, we find that the distributions of wet spells appear to exhibit universality in the following sense. While both ocean and land regions with high seasonal rainfall accumulation (humid regions; e. g., India, Amazon, Pacific Ocean) show a predominance of 2-4 day wet spells, those regions with low seasonal rainfall accumulation (arid regions; e. g., South Atlantic, South Australia) exhibit a wet spell duration distribution that is essentially exponential in nature, with a peak at 1 day. The behavior that we observed for wet spells is reversed for the dry spell characteristics. In other words, the main contribution to the dry part of the season, in terms of the number of nonrainy days, appears to come from 3-4 day dry spells in the arid regions, as opposed to 1 day dry spells in the humid regions. The total rainfall accumulated in each wet spell has also been analyzed, and we find that the major contribution to seasonal rainfall for arid regions comes from 1-5 day wet spells; however, for humid regions, this contribution comes from wet spells of duration as long as 30 days. We also explore the role of chance as well as the influence of organized convection in determining some of the observed features.

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

Wykorzystanie gier decyzyjnych/symulacyjnych w naukach społecznych. Wybrane problemy

Treścią publikacji jest przedstawienie wybranych problemów prognozowania w naukach społecznych. W artykule skoncentrowano się na metodzie gier decyzyjnych/symulacyjnych, które – zwłaszcza wraz z rozwojem teorii gier oraz komputerów – są coraz częściej wykorzystywane w wielu dziedzinach. Na wybranych przykładach gier decyzyjnych/symulacyjnych – Poznań International Model United Nations 2013/POZiMUN; S.E.N.S.E. a także gry sieciowej EVE Online – wskazano jak ważne są takie ćwiczenia, by móc precyzyjniej przewidywać przyszłość. Zwrócono także szczególną uwagę na kwestię przypadku oraz czynników zakłócających, które mogą destabilizować proces przewidywania. Poruszono ponadto problem podejmowania decyzji w aspekcie klasycznej oraz kwantowej logiki.

[Book review] Chance encounters: a first course in data analysis and inference

Book review of: Chance Encounters: A First Course in Data Analysis and Inference by Christopher J. Wild and George A.F. Seber 2000, John Wiley & Sons Inc. Hard-bound, xviii + 612 pp ISBN 0-471-32936-3

Cosmological Constraints from Measurements of Type Ia Supernovae Discovered During the First 1.5 Yr of the Pan-STARRS1 Survey

We present griz_P1 light curves of 146 spectroscopically confirmed Type Ia supernovae (SNe Ia; 0.03 < z < 0.65) discovered during the first 1.5 yr of the Pan-STARRS1 Medium Deep Survey. The Pan-STARRS1 natural photometric system is determined by a combination of on-site measurements of the instrument response function and observations of spectrophotometric standard stars. We find that the systematic uncertainties in the photometric system are currently 1.2% without accounting for the uncertainty in the Hubble Space Telescope Calspec definition of the AB system. A Hubble diagram is constructed with a subset of 113 out of 146 SNe Ia that pass our light curve quality cuts. The cosmological fit to 310 SNe Ia (113 PS1 SNe Ia + 222 light curves from 197 low-z SNe Ia), using only supernovae (SNe) and assuming a constant dark energy equation of state and flatness, yields w = -1.120^+0.360_-0.206(Stat)^+0.269_0.291(Sys). When combined with BAO+CMB(Planck)+H₀, the analysis yields Ω_M = 0.280^+0.013_0.012 and w = -1.166^+0.072_-0.069 including all identified systematics. The value of w is inconsistent with the cosmological constant value of -1 at the 2.3σ level. Tension endures after removing either the baryon acoustic oscillation (BAO) or the H₀ constraint, though it is strongest when including the H₀ constraint. If we include WMAP9 cosmic microwave background (CMB) constraints instead of those from Planck, we find w = -1.124^+0.083_-0.065, which diminishes the discord to <2σ. We cannot conclude whether the tension with flat ΛCDM is a feature of dark energy, new physics, or a combination of chance and systematic errors. The full Pan-STARRS1 SN sample with ∼three times as many SNe should provide more conclusive results.

Nietzsche's eternal recurrence of the same : the effect of logic abridgement, contradictions and inconsistencies

I will argue that the doctrine of eternal recurrence of the same no better interprets cosmology than pink elephants interpret zoology. I will also argue that the eternal-reiurn-of-the-same doctrine as what Magnus calls "existential imperative" is without possibility of application and thus futile. To facilitate those arguments, the validity of the doctrine of the eternal recurrence of the same will be tested under distinct rubrics. Although each rubric will stand alone, one per chapter, as an evaluation of some specific aspect of eternal recurrence, the rubric sequence has been selected to accommodate the identification of what I shall be calling logic abridgments. The conclusions to be extracted from each rubric are grouped under the heading CONCLUSION and appear immediately following rubric ten. Then, or if, at the end of a rubric a reader is inclined to wonder which rubric or topic is next, and why, the answer can be found at the top of the following page. The question is usually answered in the very first sentence, but always answered in the first paragraph. The first rubric has been placed in order by chronological entitlement in that it deals with the evolution of the idea of eternal recurrence from the time of the ancient Greeks to Nietzsche's August, 1881 inspiration. This much-recommended technique is also known as starting at the beginning. Rubric 1 also deals with 20th. Century philosophers' assessments of the relationship between Nietzsche and ancient Greek thought. The only experience of E-R, Zarathustra's mountain vision, is second only because it sets the scene alluded to in following rubrics. The third rubric explores .ii?.ih T jc,i -I'w Nietzsche's evaluation of rationality so that his thought processes will be understood appropriately. The actual mechanism of E-R is tested in rubric four...The scientific proof Nietzsche assembled in support of E-R is assessed by contemporary philosophers in rubric five. E-R's function as an ethical imperative is debated in rubrics six and seven.. .The extent to which E-R fulfills its purpose in overcoming nihilism is measured against the comfort assured by major world religions in rubric eight. Whether E-R also serves as a redemption for revenge is questioned in rubric nine. Rubric ten assures that E-R refers to return of the identically same and not merely the similar. In addition to assemblage and evaluation of all ten rubrics, at the end of each rubric a brief recapitulation of its principal points concludes the chapter. In this essay I will assess the theoretical conditions under which the doctrine cannot be applicable and will show what contradictions and inconsistencies follow if the doctrine is taken to be operable. Harold Alderman in his book Nietzsche's Gift wrote, the "doctrine of eternal recurrence gives us a problem not in Platonic cosmology, but in Socratic selfreflection." ^ I will illustrate that the recurrence doctrine's cosmogony is unworkable and that if it were workable, it would negate self-reflection on the grounds that selfreflection cannot find its cause in eternal recurrence of the same. Thus, when the cosmology is shown to be impossible, any expected ensuing results or benefits will be rendered also impossible. The so-called "heaviest burden" will be exposed as complex, engrossing "what if speculations deserving no linkings to reality. To identify ^Alderman p. 84 abridgments of logic, contradictions and inconsistencies in Nietzsche's doctrine of eternal recurrence of the same, I. will examine the subject under the following schedule. In Chapter 1 the ancient origins of recurrence theories will be introduced. ..This chapter is intended to establish the boundaries within which the subsequent chapters, except Chapter 10, will be confined. Chapter 2, Zarathustra's vision of E-R, assesses the sections of Thus Spoke Zarathustra in which the phenomenon of recurrence of the same is reported. ..Nihilism as a psychological difficulty is introduced in this rubric, but that subject will be studied in detail in Chapter 8. In Chapter 2 the symbols of eternal recurrence of the same will be considered. Whether the recurrence image should be of a closed ring or as a coil will be of significance in many sections of my essay. I will argue that neither symbolic configuration can accommodate Nietzsche's supposed intention. Chapter 3 defends the description of E-R given by Zarathustra. Chapter 4, the cosmological mechanics of E-R, speculates on the seriousness with which Nietzsche might have intended the doctrine of eternal recurrence to be taken. My essay reports, and then assesses, the argument of those who suppose the doctrine to have been merely exploratory musings by Nietzsche on cosmological hypotheses...The cosmogony of E-R is examined. In Chapter 5, cosmological proofs tested, the proofs for Nietzsche's doctrine of return of the same are evaluated. This chapter features the position taken by Martin ' Heidegger. My essay suggests that while Heidegger's argument that recurrence of the same is a genuine cosmic agenda is admirable, it is not at all persuasive. Chapter 6, E-R is an ethical imperative, is in essence the reporting of a debate between two scholars regarding the possibility of an imperative in the doctrine of recurrence. Their debate polarizes the arguments I intend to develop. Chapter 7, does E-R of the same preclude alteration of attitudes, is a continuation of the debate presented in Chapter 6 with the focus shifted to the psychological from the cosmological aspects of eternal recurrence of the same. Chapter 8, Can E-R Overcome Nihilism?, is divided into two parts. In the first, nihilism as it applies to Nietzsche's theory is discussed. ..In part 2, the broader consequences, sources and definitions of nihilism are outlined. My essay argues that Nietzsche's doctrine is more nihilistic than are the world's major religions. Chapter 9, Is E-R a redemption for revenge?, examines the suggestion extracted from Thus Spoke Zarathustra that the doctrine of eternal recurrence is intended, among other purposes, as a redemption for mankind from the destructiveness of revenge. Chapter 10, E-R of the similar refuted, analyses a position that an element of chance can influence the doctrine of recurrence. This view appears to allow, not for recurrence of the same, but recurrence of the similar. A summary will recount briefly the various significant logic abridgments, contradictions, and inconsistencies associated with Nietzsche's doctrine of eternal recurrence of the same. In the 'conclusion' section of my essay my own opinions and observations will be assembled from the body of the essay.

Education, sport and myth in the community of Glengarry, Ontario : the athletic career of Roderick R. McLennan. 260 St. Catharines, Ont. : Faculty of Education, Brock University ;

This study examined how the athletic career of Roderick R. McLennan contributed to the popularization and subsequent development of Caledonian games in Ontario during the latter nineteenth century. Initially, the development of Caledonian games during the 1800s was examined to provide a contextual framework for McLennan's career. This investigation revealed that the games emerged from rural athletic events at pioneer working bees in the first quarter of the nineteenth century to regional sporting events by the mid-1800s, and finally into annual federated Caledonian games in 1870. Noteworthy primary source material for this chapter included the John MacGillivray Papers at the National Archives of Canada, the Scottish American Journal (NY) and the files retained by the Glengarry Sport Hall of Fame in Maxville, Ontario. Following the investigation of Caledonian games, McLennan's early athletic career was studied. Analysis of the Roderick and Farquhar McLennan Papers at the Archives of Ontario and the newspapers from the period revealed that McLennan rose to popularity in 1865 through a "Championship of the World" hammer throwing match in Cornwall and two "Starring Tours". The next chapter examined the height of McLennan's career through an investigation of the Roderick McLennan versus Donald Dinnie rivalry of the early .. n 1870s. It was detennined that the rivalry between McLennan and Dinnie, the champion athlete of Highland games in Scotland, was a popular attraction and had an impact on the Toronto and Montreal games of 1870 and the Toronto games of 1872. Finally, the athletic records established by McLennan during the 1860s and 1870s were investigated. These records were examined through the context of a media controversy over McLennan's feats that developed in the early 1880s between two newspapers. This controversy erupted between the Toronto Mail and the Spirit of the Times. Caledonian games in Canada have only been briefly examined and a thorough examination of prominent Canadian figures in this context has yet to be undertaken. This study unearths a prominent Canadian athlete of Scottish decent and details his involvement in the Caledonian games of nineteenth century Ontario.

The effects of computer assisted interactive fiction on the development of reading comprehension in grade five students

This study was undertaken in order to determine the effects of playing computer based text adventure games on the reading comprehension gains of students. Forty-five grade five students from one elementary school were randomly assigned to experimental and control groups, and were tested with regard to ability, achievement and reading skills. An experimental treatment, consisting of playing computer based interactive fiction games of the student's choice for fifteen minutes each day over an eight-week period, was administered. A comparison treatment engaged the control group in sustained silent reading of materials of the student's choice for an equal period of time. Following the experimental period all students were post-tested with an alternate form of the pre-test in reading skills, and gain scores were analysed. It was found that there were no significant differences in the gain scores of the experimental and control groups for overall reading comprehenSion, but the experimental group showed greater gains than the control group in the structural analysis reading sub-skill. Extreme variance in the data made generalization very difficult, but the findings indicated a potential for computer based interactive fiction as a useful tool for developing reading sl

The Poetics of Game Narratives

In this final week we will look at the tensions between ludology and narratology in games design, in effect how the agency of games has been reconciled with the dramatic requirements (and lack of agency) in narrative. I will argue that there are two broad approaches, the mainstream method of concentrating in the Fabula, and a method pioneered by many indie games of fusing narrative and play. We will look in more detail at what this might mean in terms of thematic cohesion, diegetic choices, and mechanics and metaphor. Finally we look at Spec Ops: The Line, as a rare example of a AAA title that takes this fusion approach. Looking at how the game uses many of the techniques we have explored.