Pathway analysis of genome-wide association study data in primary biliary cirrhosisa

Genome-wide association studies (GWAS) have successfully identified several genetic loci associated with inherited predisposition to primary biliary cirrhosis (PBC), the most common autoimmune disease of the liver. Pathway-based tests constitute a novel paradigm for GWAS analysis. By evaluating genetic variation across a biological pathway (gene set), these tests have the potential to determine the collective impact of variants with subtle effects that are individually too weak to be detected in traditional single variant GWAS analysis. To identify biological pathways associated with the risk of development of PBC, GWAS of PBC from Italy (449 cases and 940 controls) and Canada (530 cases and 398 controls) were independently analyzed. The linear combination test (LCT), a recently developed pathway-level statistical method was used for this analysis. For additional validation, pathways that were replicated at the P <0.05 level of significance in both GWAS on LCT analysis were also tested for association with PBC in each dataset using two complementary GWAS pathway approaches. The complementary approaches included a modification of the gene set enrichment analysis algorithm (i-GSEA4GWAS) and Fisher's exact test for pathway enrichment ratios. Twenty-five pathways were associated with PBC risk on LCT analysis in the Italian dataset at P<0.05, of which eight had an FDR<0.25. The top pathway in the Italian dataset was the TNF/stress related signaling pathway (p=7.38×10 -4, FDR=0.18). Twenty-six pathways were associated with PBC at the P<0.05 level using the LCT in the Canadian dataset with the regulation and function of ChREBP in liver pathway (p=5.68×10-4, FDR=0.285) emerging as the most significant pathway. Two pathways, phosphatidylinositol signaling system (Italian: p=0.016, FDR=0.436; Canadian: p=0.034, FDR=0.693) and hedgehog signaling (Italian: p=0.044, FDR=0.636; Canadian: p=0.041, FDR=0.693), were replicated at LCT P<0.05 in both datasets. Statistically significant association of both pathways with PBC genetic susceptibility was confirmed in the Italian dataset on i-GSEA4GWAS. Results for the phosphatidylinositol signaling system were also significant in both datasets on applying Fisher's exact test for pathway enrichment ratios. This study identified a combination of known and novel pathway-level associations with PBC risk. If functionally validated, the findings may yield fresh insights into the etiology of this complex autoimmune disease with possible preventive and therapeutic application.^

The history of technology in education. A comparative study and forecast

Area, launched in 1999 with the Bologna Declaration, has bestowed such a magnitude and unprecedented agility to the transformation process undertaken by European universities. However, the change has been more profound and drastic with regards to the use of new technologies both inside and outside the classroom. This article focuses on the study and analysis of the technology’s history within the university education and its impact on teachers, students and teaching methods. All the elements that have been significant and innovative throughout the history inside the teaching process have been analyzed, from the use of blackboard and chalk during lectures, the use of slide projectors and transparent slides, to the use of electronic whiteboards and Internet nowadays. The study is complemented with two types of surveys that have been performed among teachers and students during the school years 1999 - 2011 in the School of Civil Engineering at the Polytechnic University of Madrid. The pros and cons of each of the techniques and methodologies used in the learning process over the last decades are described, unfolding how they have affected the teacher, who has evolved from writing on a whiteboard to project onto a screen, the student, who has evolved from taking handwritten notes to download information or search the Internet, and the educational process, that has evolved from the lecture to acollaborative learning and project-based learning. It is unknown how the process of learning will evolve in the future, but we do know the consequences that some of the multimedia technologies are having on teachers, students and the learning process. It is our goal as teachers to keep ourselves up to date, in order to offer the student adequate technical content, while providing proper motivation through the use of new technologies. The study provides a forecast in the evolution of multimedia within the classroom and the renewal of the education process, which in our view, will set the basis for future learning process within the context of this new interactive era.

The Influence of Space Layout, Technology and Teaching Approach on Student Learning: An Architectural Technology Perspective

Some would argue that there is a need for the traditional lecture format to be rethought in favour of a more active approach. However, this must form part of a bipartite strategy, considered in conjunction with the layout of any new space to facilitate alternative learning and teaching methods. With this in mind, this paper begins to examine the impact of the learning environment on the student learning experience, specifically focusing on students studying on the Architectural Technology and Management programme at Ulster University. The aim of this study is two-fold: to increase understanding of the impact of learning space layout, by taking a student centered approach; and to gain an appreciation of how technology can impact upon the learning space. The study forms part of a wider project being undertaken at Ulster University known as the Learning Landscape Transition Project, exploring the relationship between learning, teaching and space layout. Data collection was both qualitative and quantitative, with use of a case study supported by a questionnaire based on attitudinal scaling. A focus group was also used to further analyse the key trends resulting from the questionnaire. The initial results suggest that the learning environment, and the technology within it, can not only play an important part in the overall learning experience of the student, but also assist with preparation for the working environment to be experienced in professional life.

Mathematical notebook, and commonplace book, circa 1689-1769

Manuscript notebook, possibly kept by Harvard students, containing 17th century English transcriptions of arithmetic and geometry texts, one of which is dated 1689-1690; 18th century transcriptions from John Ward’s “The Young Mathematician’s Guide”; and notes on physics lectures delivered by John Winthrop, the Hollis Professor of Mathematics and Natural Philosophy at Harvard from 1738 to 1779. The notebook also contains 18th century reading notes on Henry VIII, Tudor succession, and English history from Daniel Neal’s “The History of the Puritans” and David Hume’s “History of England,” and notes on Ancient history, taken mainly from Charles Rollin’s “The Ancient History of the Egyptians, Carthaginians, Assyrians, Babylonians, Medes and Persians, Macedonians and Grecians.” Additionally included are an excerpt from Plutarch’s “Lives” and transcriptions of three articles from “The Gentleman’s Magazine, and Historical Chronicle,” published in 1769: “A Critique on the Works of Ovid”; a book review of “A New Voyage to the West-Indies”; and “Genuine Anecdotes of Celebrated Writers, &.” The flyleaf contains the inscription “Semper boni aliquid operis facito ut diabolus te semper inveniat occupatum,” a variation on a quote of Saint Jerome that translates approximately as “Always good to do some work so that the devil may always find you occupied.” In the seventeenth and eighteenth centuries, Harvard College undergraduates often copied academic texts and lecture notes into personal notebooks in place of printed textbooks. Winthrop used Ward’s textbook in his class, while the books of Hume, Neal, and Rollin were used in history courses taught at Harvard in the 18th century.

Guide to the study and use of reference books; a manual for librarians, teachers and students,

"Limited to those of a strictly reference character, and to the most useful works in the English language, with some exceptions in other languages."

Guide to the study and use of reference books,

Accompanied by "Supplement 1911-1913, by Isadore Gilbert Mudge." (48 p. 24 cm.) Published: Chicago, Ill., American library association publishing board, 1914.

Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis

Objectives: To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. Methods: We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC(0-8)) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). Results: All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC(0-8) indinavir decreased by 4.4% (90% CI, -27.5% to -26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, -37.3% to +9%, P=0.25) in phase III. Control group mean AUC(0-8) decreased by 21.5% (90% CI, -43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle-oindinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle-indinavir trials revealed a non-significant pooled mean difference of 1% in AUC(0-8) (95% CI, -53% to 55%, P=0.97). Conclusions: Indinavir levels were not reduced significantly in the presence of milk thistle.

Effect of Al2O3 and Cr2O3 on loquidus temperatures in the cristobalite and tridymite primary phase fields of the MgO-"FeO"-SiO2 ststem in equilibrium with metallic iron

The effects of alumina and chromite impurities on the liquidus temperatures in the cristobalite/tridymite (SiO2) primary phase fields in the MgO-FeO-SiO, system in equilibrium with metallic iron have been investigated experimentally. Using high temperature equilibration and quenching followed by electron probe X-ray microanalysis (EPMA), liquiclus isotherms have been determined in the temperatures range 1 673 to 1 898 K. The results are presented in the form of pseudo-ternary sections of the MgO-FeO-SiO, system at 2, 3 and 5 wt% Al2O3, 2 wt% Cr2O3, and 2 wt% Cr2O3+2 wt% Al2O3. The study enables the liquidus to be described for a range of SiO2/MgO and MgO/FeO ratios. It was found that liquiclus temperatures in the cristobalite and tridymite primary phase fields, decrease significantly with the addition of Al2O3 and Cr2O3.

Good practice guide in learning and teaching

Once again this publication is produced to celebrate and promote good teaching and learning support and to offer encouragement to those imaginative and innovative staff who continue to wish to challenge students to learn to maximum effect. It is hoped that others will pick up some good ideas from the articles contained in this volume. We have again changed our approach for this 2007/08 edition (our fifth) of the Aston Business School Good Practice Guide. As before, some contributions were selected from those identifying interesting best practice on their Annual Module Reflection Forms in 2006/2007. Brookes? contribution this year is directly from her annual reflection. Other contributors received HELM (Research Centre in Higher Education Learning and Management) small research grants in 2006/2007. Part of the conditions were for them to write an article for this publication. We have also been less tight on the length of the articles this year. Some contributions are, therefore, on the way to being journal articles. HELM will be working with these authors to help develop these for publication. Looking back over the last five years it is brilliant to see how many different people have contributed over the years and, therefore, how much innovative learning and teaching work has been taking place in ABS over this time. In the first edition we were just pleased for people to write a few pages on their teaching. Now things have changed dramatically. The majority of the articles are grounded in empirical research (some funded by HELM small research grants) and Palmer?s article was produced as part of the University?s Postgraduate Certificate in Learning and Teaching. Most encouraging of all, four of this year?s articles have since been developed further and submitted to refereed journals. We await news of publication as we go to press. It is not surprising that how to manage large groups still remains a central theme of the articles, ABS has a large and still growing student body. Essex and Simpson have looked at trying to encourage students to attend taught sessions, on the basis that there is a strong correlation between attendance and higher performance. Their findings are forming the platform of a further study currently being carried out in the Undergraduate Programme. A number of the other articles concentrate on trying to encourage students to engage with study in an innovative way. This is particularly obvious in Shaw?s work. Everyone who has been around campus lately has had evidence that the students on Duncan?s modules have clearly been inspired. I found myself, for example, playing golf in the student dining room as part of this initiative! The articles by Jarzabkowski & Guilietti and Ho involved much larger surveys. This is another first for the Good Practice Guide and marks the first step on what will clearly be larger research efforts for these authors in this area. We look forward to the journal publications which will result from this work. The last articles are the result of HELM?s hosting of the national conference of the Higher Education Academy?s Business, Management, Accounting and Finance (BMAF) Subject Centre Conference in May 2007. Belal and Foster have written about their impressions of the Conference and Andrews has included the paper she gave. The papers on employability and widening participation are the centre of HELM?s current work. In the second volume we mentioned the launch of the School?s Research Centre in Higher Education Learning and Management (HELM). Since then HELM has stimulated a lot of activity across the School (and University) particularly linking research and teaching. A list of the HELM seminars for 2007/2008 is listed as Appendix 1 of this publication. Further details can be obtained from Catherine Foster (c.s.foster@aston.ac.uk), who coordinates the HELM seminars. We have also been working on a list of target journals to guide ABS staff who wish to publish in this area. These are included as Appendix 2 of this publication. May I thank the contributors for taking time out of their busy schedules to write the articles and to Julie Green, the Quality Manager, for putting the varying diverse approaches into a coherent and publishable form and for agreeing to fund the printing of this volume.

Developments in assessment and teaching methodologies in modern languages in England and France in response to educational reform (1975-1985)

This comparative study considers the main causative factors for change in recent years in the teaching of modern languages in England and France and seeks to contribute, in a general sense, to the understanding of change in comparable institutions. In England by 1975 the teaching of modern languages in the comprehensive schools was seen to be inappropriate to the needs of children of the whole ability-range. A combination of the external factor of the Council of Europe initiative in devising a needs-based learning approach for adult learners, and the internal factor of teacher-based initiatives in developing a graded-objectives learning approach for the less-able, has reversed this situation to some extent. The study examines and evaluates this reversal, and, in addition, assesses teachers' attitudes towards, and understanding of, the changes involved. In France the imposition of `la reforme Haby' in 1977 and the creation of `le college unique' were the main external factors for change. The subsequent failure of the reform and the socialist government's support of decentralisation policies returning the initiative for renewal to schools are examined and evaluated, as are the internal factors for changes in language-teaching - `groupes de niveau' and the creation of `equipes pedagogiques'. In both countries changes in the function of examinations at 15/16 plus are examined. The final chapter compared the changes in both education systems.

The impact of the language barrier on the management of multinational companies : a case study and survey, based exploration of the impact of the language barrier on the strategies, policies and systems by which multinational companies manage their subsidaries

The thesis begins with a conceptual model of the way that language diversity affects the strategies, organisation and subsidiary control policies of multinational companies. The model is based solely on the researcher'’ personal experience of working in a variety of international management roles, but in Chapter 2 a wide-ranging review of related academic literature finds evidence to support the key ideas. The model is developed as a series of propositions which are tested in a comparative case study, refined and then re-tested in a global survey of multinational subsidiaries. The principal findings of the empirical phases of the thesis endorse the main tenets of the model: - That language difference between parent and subsidiary will impair communication, create mistrust and impede relationship development. - That subsequently the feelings of uncertainty, suspicion and mistrust will influence the decisions taken by the parent company. - They will have heightened sensitivity to language issues and will implement policies to manage language differences. - They will adopt low-risk strategies in host countries where they are concerned about language difference. - They will use organisational and manpower strategies to minimise the consequences and risks of the communications problems with the subsidiary. - As a consequence the level of integration and knowledge flow between parent and subsidiary will be curtailed. - They will adopt styles of control that depend least on their ability to communicate with their subsidiary. Although there is adequate support for all of the above conclusions, on some key points the evidence of the Case Studies and Survey is contradictory. The thesis, therefore, closes with an agenda for further research that would address these inconsistencies.

Quality management (QM) implementation in the Kuwaiti Oil Industry:An empirical study and a proposed generic framework

In an Arab oil producing country in the Middle East such as Kuwait, Oil industry is considered as the main and most important industry of the country. This industry’s importance emerged from the significant role it plays in both country’s national economy and also global economy. Moreover, Oil industry’s criticality comes from its interconnectivity with national security and power in the Middle East region. Hence, conducting this research in this crucial industry had certainly added values to companies in this industry as it investigated thoroughly the main components of the TQM implementation process and identified which components affects significantly TQM’s implementation and its gained business results. In addition, as the Oil sector is a large sector that is known for its richness of employees with different national cultures and backgrounds. Thus, this culture-heterogeneous industry seems to be the most appropriate environment to address and satisfy a need in the literature to investigate the national culture values’ effects on TQM implementation process. Furthermore, this research has developed a new conceptual model of TQM implementation process in the Kuwaiti Oil industry that applies in general to operations and productions organizations at the Kuwaiti business environment and in specific to organizations in the Oil industry, as well it serves as a good theoretical model for improving operations and production level of the oil industry in other developing and developed countries. Thus, such research findings minimized the literature’s gap found the limited amount of empirical research of TQM implementation in well-developed industries existing in an Arab, developing countries and specifically in Kuwait, where there was no coherent national model for a universal TQM implementation in the Kuwaiti Oil industry in specific and Kuwaiti business environment in general. Finally, this newly developed research framework, which emerged from the literature search, was validated by rigorous quantitative analysis tools including SPSS and Structural Equation Modeling. The quantitative findings of questionnaires collected were supported by the qualitative findings of interviews conducted.

Perceptions of learning and teaching quality in Higher Education:developing a culture of co-creation of value

Perceptions about the quality of learning and teaching in Higher Education has for many years focused upon the application of market based principles. This includes the notion of students as “customers” of the Higher Education Institutions (HEI) service. We argue that the application of the customer analogy is unhelpful however, as students this approach is likely to affect student expectations about the service and their judgements about its quality. The purpose of this paper is to propose a study consisting of a series of interventions to develop a culture of value co-creation at a UK based HEI. By introducing CCV principles, it is hoped to steer students away from seeing themselves as “customers”, and passive recipients of in the learning and teaching process, to one where they take responsibility for their own learning experience, to be explored and acted upon in partnership with their lecturers and other stakeholders.