The Lausanne Institutional Biobank: a new resource to catalyse research in personalised medicine and pharmaceutical sciences.

Breakthrough technologies which now enable the sequencing of individual genomes will irreversibly modify the way diseases are diagnosed, predicted, prevented and treated. For these technologies to reach their full potential requires, upstream, access to high-quality biomedical data and samples from large number of properly informed and consenting individuals and, downstream, the possibility to transform the emerging knowledge into a clinical utility. The Lausanne Institutional Biobank was designed as an integrated, highly versatile infrastructure to harness the power of these emerging technologies and catalyse the discovery and development of innovative therapeutics and biomarkers, and advance the field of personalised medicine. Described here are its rationale, design and governance, as well as parallel initiatives which have been launched locally to address the societal, ethical and technological issues associated with this new bio-resource. Since January 2013, inpatients admitted at Lausanne CHUV University Hospital have been systematically invited to provide a general consent for the use of their biomedical data and samples for research, to complete a standardised questionnaire, to donate a 10-ml sample of blood for future DNA extraction and to be re-contacted for future clinical trials. Over the first 18 months of operation, 14,459 patients were contacted, and 11,051 accepted to participate in the study. This initial 18-month experience illustrates that a systematic hospital-based biobank is feasible; it shows a strong engagement in research from the patient population in this University Hospital setting, and the need for a broad, integrated approach for the future of medicine to reach its full potential.

The homeostatic psyche: Freudian theory and somatic markers.

After years of reciprocal lack of interest, if not opposition, neuroscience and psychoanalysis are poised for a renewed dialogue. This article discusses some aspects of the Freudian metapsychology and its link with specific biological mechanisms. It highlights in particular how the physiological concept of homeostasis resonates with certain fundamental concepts of psychoanalysis. Similarly, the authors underline how the Freud and Damasio theories of brain functioning display remarkable complementarities, especially through their common reference to Meynert and James. Furthermore, the Freudian theory of drives is discussed in the light of current neurobiological evidences of neural plasticity and trace formation and of their relationships with the processes of homeostasis. The ensuing dynamics between traces and homeostasis opens novel avenues to consider inner life in reference to the establishment of fantasies unique to each subject. The lack of determinism, within a context of determinism, implied by plasticity and reconsolidation participates in the emergence of singularity, the creation of uniqueness and the unpredictable future of the subject. There is a gap in determinism inherent to biology itself. Uniqueness and discontinuity: this should today be the focus of the questions raised in neuroscience. Neuroscience needs to establish the new bases of a "discontinuous" biology. Psychoanalysis can offer to neuroscience the possibility to think of discontinuity. Neuroscience and psychoanalysis meet thus in an unexpected way with regard to discontinuity and this is a new point of convergence between them.

The Implied Book and the Narrative Text. On a Blind Spot in Narratological Theory - from a Media Studies Perspective

The article is concerned with the formal definition of a largely unnoticed factor in narrative structure. Based on the assumptions that (1) the semantics of a written text depend, among other factors, directly on its visual alignment in space, that (2) the formal structure of a text has to meet that of its spatial presentation and that (3) these assumptions hold true also for narrative texts (which, however, in modern times typically conceal their spatial dimensions by a low-key linear layout), it is argued that, how ever low-key, the expected material shape of a given narrative determines the configuration of its plot by its author. The ,implied book' thus denotes an author's historically assumable, not necessarily conscious idea of how his text, which is still in the process of creation, will be dimensionally presented and under these circumstances visually absorbed. Assuming that an author's knowledge of this later (potentially) substantiated material form influences the composition, the implied book is to be understood as a text-genetically determined, structuring moment of the text. Historically reconstructed, it thus serves the methodical analysis of structural characteristics of a completed text.

Debating the centre : the theory of principal qualificand (mukhyavisesya) in classical Indian philosophy

The theory of language has occupied a special place in the history of Indian thought. Indian philosophers give particular attention to the analysis of the cognition obtained from language, known under the generic name of śābdabodha. This term is used to denote, among other things, the cognition episode of the hearer, the content of which is described in the form of a paraphrase of a sentence represented as a hierarchical structure. Philosophers submit the meaning of the component items of a sentence and their relationship to a thorough examination, and represent the content of the resulting cognition as a paraphrase centred on a meaning element, that is taken as principal qualificand (mukhyaviśesya) which is qualified by the other meaning elements. This analysis is the object of continuous debate over a period of more than a thousand years between the philosophers of the schools of Mimāmsā, Nyāya (mainly in its Navya form) and Vyākarana. While these philosophers are in complete agreement on the idea that the cognition of sentence meaning has a hierarchical structure and share the concept of a single principal qualificand (qualified by other meaning elements), they strongly disagree on the question which meaning element has this role and by which morphological item it is expressed. This disagreement is the central point of their debate and gives rise to competing versions of this theory. The Mïmāmsakas argue that the principal qualificand is what they call bhāvanā ̒bringing into being̒, ̒efficient force̒ or ̒productive operation̒, expressed by the verbal affix, and distinct from the specific procedures signified by the verbal root; the Naiyāyikas generally take it to be the meaning of the word with the first case ending, while the Vaiyākaranas take it to be the operation expressed by the verbal root. All the participants rely on the Pāninian grammar, insofar as the Mimāmsakas and Naiyāyikas do not compose a new grammar of Sanskrit, but use different interpretive strategies in order to justify their views, that are often in overt contradiction with the interpretation of the Pāninian rules accepted by the Vaiyākaranas. In each of the three positions, weakness in one area is compensated by strength in another, and the cumulative force of the total argumentation shows that no position can be declared as correct or overall superior to the others. This book is an attempt to understand this debate, and to show that, to make full sense of the irreconcilable positions of the three schools, one must go beyond linguistic factors and consider the very beginnings of each school's concern with the issue under scrutiny. The texts, and particularly the late texts of each school present very complex versions of the theory, yet the key to understanding why these positions remain irreconcilable seems to lie elsewhere, this in spite of extensive argumentation involving a great deal of linguistic and logical technicalities. Historically, this theory arises in Mimāmsā (with Sabara and Kumārila), then in Nyāya (with Udayana), in a doctrinal and theological context, as a byproduct of the debate over Vedic authority. The Navya-Vaiyākaranas enter this debate last (with Bhattoji Dïksita and Kaunda Bhatta), with the declared aim of refuting the arguments of the Mïmāmsakas and Naiyāyikas by bringing to light the shortcomings in their understanding of Pāninian grammar. The central argument has focused on the capacity of the initial contexts, with the network of issues to which the principal qualificand theory is connected, to render intelligible the presuppositions and aims behind the complex linguistic justification of the classical and late stages of this debate. Reading the debate in this light not only reveals the rationality and internal coherence of each position beyond the linguistic arguments, but makes it possible to understand why the thinkers of the three schools have continued to hold on to three mutually exclusive positions. They are defending not only their version of the principal qualificand theory, but (though not openly acknowledged) the entire network of arguments, linguistic and/or extra-linguistic, to which this theory is connected, as well as the presuppositions and aims underlying these arguments.

Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer.

PURPOSE: Recurrent head and neck cancer is associated to a poor survival prognosis. A high toxicity rate is demonstrated when surgery and/or radiotherapy and/or chemotherapy are combined. Furthermore, the duration of treatment is often not ethically compatible with the expected survival (median survival<1year). Normal tissues tolerance limits the use of reirradiation and stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. After completion of a feasibility study, results of a multicentric study (Lille, Nancy & Nice) using SBRT with cetuximab are reported. The aim of the study was to deliver non toxic short course SBRT (2weeks) in order to get the same local control as the one demonstrated with longer protocols. METHODS AND MATERIALS: Patients with inoperable recurrent, or new primary tumor in a previously irradiated area, were included (WHO<3). Reirradiation (RT) dose was 36Gy in six fractions of 6Gy to the 85% isodose line covering 95% of the PTV with 5 injections of concomitant cetuximab (CT). All patients had previous radiotherapy, 85% had previous surgery and 48% previous chemotherapy. RESULTS: Between 11/2007 and 08/2010, 60 were included (46 men and 14 women), 56 received CT+RT, 3 were not treated and 1 received only CT. Median age was 60 (42-87)) and all 56 patients had squamous carcinoma and received concomitant cetuximab. Mean time between previous radiotherapy and the start of SBRT was 38months. Cutaneous toxicity was observed for 41 patients. There was one toxic death from hemorrhage and denutrition. Median follow-up was 11.4months. At 3months, response rate was 58.4% (95% CI: 43.2-72.4%) and disease control rate was 91.7% (95% CI: 80.0-97.7%). The one-year OS rate was 47.5% (95% CI: 30.8-62.4). CONCLUSION: These results suggest that short SBRT with cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. This combination may be the reference treatment is this population.

Standards and service offshoring in India: Moving beyond industry and institutional specificities

Résumé Cet article examine le rôle joué par les normes internationales techniques dans la mondialisation des activités de service. Différentes approches d'économie considèrent que les spécificités des activités de services sont un frein à leur délocalisation, à leur industrialisation et à leur normalisation. A l'opposé de ces approches centrées sur les spécificités des activités de services, les approches d'économie politique internationale mettent en avant l'existence de configurations conflictuelles de pouvoir à l'oeuvre dans l'internationalisation des activités de services et ce, au-delà des limites sectorielles et nationales. Cet article examine le cas du secteur des centres d'appels et, plus généralement, celui de la sous-traitance des services aux entreprises (BPO) en Inde. Nos résultats suggèrent que les normes techniques sont importantes dans le secteur étudié, alors même que ces types de services sont conventionnellement identifiés comme étant peu susceptibles d'être soumis à des normes. Une perspective d'économie politique sur la normalisation des activités de service souligne comment la problématique du pouvoir investit la normalisation technique d'une dimension plus progressive à travers les thématiques du "travailleur", du "consommateur", ou de "l'environnement". Abstract This paper explores the role of international standards in the much-debated globalisation of the service economy. Various strands of economic analyses consider that core attributes of services affect their ability to be reliably delocalised, industrialised, and standardised. In contrast, international political economy approaches draw attention to power configurations supporting conflicting use of standards across industries and nations. The paper examines the case of the rising Indian service industry in customer centres and business process outsourcing to probe these opposing views. Our findings suggest that standards matter in types of services that conventional economic analyses identify as unlikely to be standardised, and that the standards used in the Indian BPO industry are widely accepted. Despite little conflict in actual definitions of market requirements, an international political economy perspective on service standardisation highlights the importance of potential power issues related to workers', consumers', and environmental concerns likely to be included in more progressive forms of standardisation.

Institutional change and the evolution of the regulatory state: evidence from the Swiss case

This article examines institutional change in a case that was expected to be particularly resilient but showed considerable structural transformation: the institutionalization of the regulatory state in Switzerland. This process is illustrated through the establishment of independent regulatory agencies (IRAs) in four areas: banking and finance; telecommunications; electricity; and competition. The theoretical framework developed by Streeck, Thelen and Mahoney is used to explore hypotheses about the modes of institutional change, with the methodology of diachronic within-case study. Results confirm only partially the expectations, pointing to layering and displacement as the prevalent modes of change. The concluding part discusses the type and the direction of change as additional explanatory factors.

Effective corporate governance : experimental evidence on international auditors'judgments and the contribution of financial accounting education

1 Summary This dissertation deals with two major aspects of corporate governance that grew in importance during the last years: the internal audit function and financial accounting education. In three essays, I contribute to research on these topics which are embedded in the broader corporate governance literature. The first two essays consist of experimental investigations of internal auditors' judgments. They deal with two research issues for which accounting research lacks evidence: The effectiveness of internal controls and the potentially conflicting role of the internal audit function between management and the audit committee. The findings of the first two essays contribute to the literature on internal auditors' judgment and the role of the internal audit function as a major cornerstone of corporate governance. The third essay theoretically examines a broader issue but also relates to the overall research question of this dissertation: What contributes to effective corporate governance? This last essay takes the perspective that the root for quality corporate governance is appropriate financial accounting education. r develop a public interest approach to accounting education that contributes to the literature on adequate accounting education with respect to corporate governance and accounting harmonization. The increasing importance of both the internal audit function and accounting education for corporate governance can be explained by the same recent fundamental changes that still affect accounting research and practice. First, the Sarbanes-Oxley Act of 2002 (SOX, 2002) and the 8th EU Directive (EU, 2006) have led to a bigger role for the internal audit function in corporate governance. Their implications regarding the implementation of audit committees and their oversight over internal controls are extensive. As a consequence, the internal audit function has become increasingly important for corporate governance and serves a new master (i.e. the audit committee) within the company in addition to management. Second, the SOX (2002) and the 8th EU Directive introduced additional internal control mechanisms that are expected to contribute to the reliability of financial information. As a consequence, the internal audit function is expected to contribute to a greater extent to the reliability of financial statements. Therefore, effective internal control mechanisms that strengthen objective judgments and independence become important. This is especially true when external- auditors rely on the work of internal auditors in the context of the International Standard on Auditing (ISA) 610 and the equivalent US Statement on Auditing Standards (SAS) 65 (see IFAC, 2009 and AICPA, 1990). Third, the harmonization of international reporting standards is increasingly promoted by means of a principles-based approach. It is the leading approach since a study of the SEC (2003) that was required by the SOX (2002) in section 108(d) was in favor of this approach. As a result, the Financial Accounting Standards Board (FASB) and the International Accounting Standards Board (IASB) commit themselves to the development of compatible accounting standards based on a principles-based approach. Moreover, since the Norwalk Agreement of 2002, the two standard setters have developed exposure drafts for a common conceptual framework that will be the basis for accounting harmonization. The new .framework will be in favor of fair value measurement and accounting for real-world economic phenomena. These changes in terms of standard setting lead to a trend towards more professional judgment in the accounting process. They affect internal and external auditors, accountants, and managers in general. As a consequence, a new competency set for preparers and users of financial statements is required. The basil for this new competency set is adequate accounting education (Schipper, 2003). These three issues which affect corporate governance are the initial point of this dissertation and constitute its motivation. Two broad questions motivated a scientific examination in three essays: 1) What are major aspects to be examined regarding the new role of the internal audit function? 2) How should major changes in standard setting affect financial accounting education? The first question became apparent due to two published literature reviews by Gramling et al. (2004) and Cohen, Krishnamoorthy & Wright (2004). These studies raise various questions for future research that are still relevant and which motivate the first two essays of my dissertation. In the first essay, I focus on the role of the internal audit function as one cornerstone of corporate governance and its potentially conflicting role of serving both management and the audit committee (IIA, 2003). In an experimental study, I provide evidence on the challenges for internal auditors in their role as servant for two masters -the audit committee and management -and how this influences internal auditors' judgment (Gramling et al. 2004; Cohen, Krishnamoorthy & Wright, 2004). I ask if there is an expectation gap between what internal auditors should provide for corporate governance in theory compared to what internal auditors are able to provide in practice. In particular, I focus on the effect of serving two masters on the internal auditor's independence. I argue that independence is hardly achievable if the internal audit function serves two masters with conflicting priorities. The second essay provides evidence on the effectiveness of accountability as an internal control mechanism. In general, internal control mechanisms based on accountability were enforced by the SOX (2002) and the 8th EU Directive. Subsequently, many companies introduced sub-certification processes that should contribute to an objective judgment process. Thus, these mechanisms are important to strengthen the reliability of financial statements. Based on a need for evidence on the effectiveness of internal control mechanisms (Brennan & Solomon, 2008; Gramling et al. 2004; Cohen, Krishnamoorthy & Wright, 2004; Solomon & Trotman, 2003), I designed an experiment to examine the joint effect of accountability and obedience pressure in an internal audit setting. I argue that obedience pressure potentially can lead to a negative influence on accountants' objectivity (e.g. DeZoort & Lord, 1997) whereas accountability can mitigate this negative effect. My second main research question - How should major changes in standard setting affect financial accounting education? - is investigated in the third essay. It is motivated by the observation during my PhD that many conferences deal with the topic of accounting education but very little is published about what needs to be done. Moreover, the Endings in the first two essays of this thesis and their literature review suggest that financial accounting education can contribute significantly to quality corporate governance as argued elsewhere (Schipper, 2003; Boyce, 2004; Ghoshal, 2005). In the third essay of this thesis, I therefore focus on approaches to financial accounting education that account for the changes in standard setting and also contribute to corporate governance and accounting harmonization. I argue that the competency set that is required in practice changes due to major changes in standard setting. As the major contribution of the third article, I develop a public interest approach for financial accounting education. The major findings of this dissertation can be summarized as follows. The first essay provides evidence to an important research question raised by Gramling et al. (2004, p. 240): "If the audit committee and management have different visions for the corporate governance role of the IAF, which vision will dominate?" According to the results of the first essay, internal auditors do follow the priorities of either management or the audit committee based on the guidance provided by the Chief Audit executive. The study's results question whether the independence of the internal audit function is actually achievable. My findings contribute to research on internal auditors' judgment and the internal audit function's independence in the broader frame of corporate governance. The results are also important for practice because independence is a major justification for a positive contribution of the internal audit function to corporate governance. The major findings of the second essay indicate that the duty to sign work results - a means of holding people accountable -mitigates the negative effect of obedience pressure on reliability. Hence, I found evidence that control .mechanisms relying on certifications may enhance the reliability of financial information. These findings contribute to the literature on the effectiveness of internal control mechanisms. They are also important in the light of sub-certification processes that resulted from the Sarbanes-Oxley Act and the 8th EU Directive. The third essay contributes to the literature by developing a measurement framework that accounts for the consequences of major trends in standard setting. Moreovér, it shows how these trends affect the required .competency set of people dealing with accounting issues. Based on this work, my main contribution is the development of a public interest approach for the design of adequate financial accounting curricula. 2 Serving two masters: Experimental evidence on the independence of internal auditors Abstract Twenty nine internal auditors participated in a study that examines the independence of internal auditors in their potentially competing roles of serving two masters: the audit committee and management. Our main hypothesis suggests that internal auditors' independence is not achievable in an institutional setting in which internal auditors are accountable to two different parties with potentially differing priorities. We test our hypothesis in an experiment in which the treatment consisted of two different instructions of the Chief audit executive; one stressing the priority of management (cost reduction) and one stressing the priority of the audit committee (effectiveness). Internal auditors had to evaluate internal controls and their inherent costs of different processes which varied in their degree of task complexity. Our main results indicate that internal auditors' evaluation of the processes is significantly different when task complexity is high. Our findings suggest that internal auditors do follow the priorities of either management or the audit committee depending on the instructions of a superior internal auditor. The study's results question whether the independence of the internal audit function is actually achievable. With our findings, we contribute to research on internal auditors' judgment and the internal audit function's independence in the frame of corporate governance.

Beyond the silence : institutional racism, social welfare and swiss citizenship

Cette thèse doctorale étudie le rôle de la citoyenneté Suisse et le modèle libérale de l'Etat social dans la production du racisme institutionnel au sein des services sociaux en Suisse. Cette thèse pose la question comment le régime de la citoyenneté Suisse rend possible et contraint les travailleurs sociaux à racialiser et discriminer leur clients avec des différences culturelles alors que les normes de l'aide sociale (normes de CSIAS) ne prévoient pas des traitements différentialistes selon la culture ou l'origine. Le modèle théorique du racisme institutionnel développé se passe sur une approche néo- institutionaliste et des ethnie and racial studies, prenant en compte le niveau individuel, collectif et institutionnel. En incluant ces deux approches, on dépasse le déterminisme des structuralistes dans les études sur le racisme institutionnel. Cette recherche qualitative montre que les travailleurs sociaux utilisent les ressources de la citoyenneté Suisse, de l'Etat social Suisse et leur expériences personnelles quand ils interagissent avec des clients. En plus, cette thèse démontre que le workfare logique en combinaison avec l'idée de l'assimilation culturelle rend possible la production d'un discours sur la nécessité de mériter d'être un membre de la communauté nationale et d'accéder à l'aide sociale. Cette compréhension néo-libérale de la citoyenneté renforce et légitime les travailleurs sociaux de racialiser et pratiquer la discrimination à l'égard de leurs clients et les rend incapable de développer une réflexivité critique. Toutefois, cette thèse montre également que les travailleurs sociaux produisent du travail social interculturel s'ils ont pu développer une telle réflexivité critique dans les institutions de l'aide sociale qui mettent en avant une conception "individuelle" de l'aide sociale.-Cette thèse vise à aller au-delà du silence qui constitue les débats publiques et la recherche sur le racisme au sein des institutions publiques en Suisse. - This thesis questions the role of the Swiss citizenship regime and the Swiss liberal social welfare model in the production of institutional racism in social services in Switzerland. Considering the absence of intercultural formal guidelines in the norms of social welfare (SKOS norms), this research investigates how the Swiss citizenship regime constrains and enables social workers to racialise and discriminate against their clients with cultural differences. This thesis develops a model of institutional racism, taking into account ethnic and racial studies and a neo-institutionalist approach on institutions, addressing the individual, collective and institutional level. In this framework, this thesis allows to overcome the structuralist determinism in the studies on institutional racism. Based on a qualitative inquiry, this research shows that social workers use the resources from the Swiss citizenship regime, social welfare model and their personal experiences when they interact with their clients. This study also shows that the workfare logic in combination with the idea of cultural assimilation enables to produce a discourse on deserving social welfare and earning membership to the national community. This neo-liberal citizenship understanding reinforces and legitimises social workers to racialise and discriminate against their clients and hinders them to develop critical reflexivity. However, this thesis also shows that social workers are able to produce intercultural social work when they could develop such a reflexivity in social services with an "individual" social welfare conceptions. This thesis aims to go beyond a persisting silence regarding public debates and research on racism in public institutions in Switzerland.