Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short‐range cell–cell signalling molecules, hormones and structural proteins. It has been implicated in a number of key biological processes including cell proliferation, migration, adhesion and signalling both in normal development and in oncogenesis. The mechanisms by which Pax6 regulates its downstream (...) targets likely involve the use of different splice variants and interactions with multiple proteins, allowing it to generate different effects in different cells. Extrapolation to developmental transcription factors in general suggests that variation in the nature of individual factors is likely to contribute to the emergence of differences between tissues. BioEssays 24:1041–1051, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the tumour infiltrated right (...) superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery. (shrink)

Introduction: making the invisible visible -- The nobility of the material -- Research at war -- The guilded age of research -- The doctor as whistle-blower -- New rules for the laboratory -- Bedside ethics -- The doctor as stranger -- Life through death -- Commissioning ethics -- No one to trust -- New rules for the bedside -- Epilogue: The price of success.

Functional imaging studies of neurologically intact adults have demonstrated that the right posterior cerebellum is activated during verb generation, semantic processing, sentence processing, and verbal fluency. Studies of patients with cerebellar damage converge to show that the cerebellum supports sentence processing and verbal fluency. However, to date there are no patient studies that investigated the specific importance of the right posterior cerebellum in language processing, because: case studies presented patients with lesions affecting the anterior cerebellum, and group studies combined patients (...) with lesions to different cerebellar regions, without specifically reporting the effects of right posterior cerebellar damage. Here we investigated whether damage to the right posterior cerebellum is critical for sentence processing and verbal fluency in four patients with focal stroke damage to different parts of the right posterior cerebellum. We examined detailed lesion location by going beyond common anatomical definitions of cerebellar anatomy, and employed a recently proposed functional parcellation of the cerebellum. All four patients experienced language difficulties that persisted for at least a month after stroke but three performed in the normal range within a year. In contrast, one patient with more damage to lobule IX than the other patients had profound long-lasting impairments in the comprehension and repetition of sentences, and the production of spoken sentences during picture description. Spoken and written word comprehension and visual recognition memory were also impaired, however, verbal fluency was within the normal range, together with object naming, visual perception and verbal short-term memory. This is the first study to show that focal damage to the right posterior cerebellum leads to language difficulties after stroke; and that processing impairments persisted in the case with most damage to lobule IX. We discuss these results in relation to current theories of cerebellar contribution to language processing. Overall, our study highlights the need for longitudinal studies of language function in patients with focal damage to different cerebellar regions, with functional imaging to understand the mechanisms that support recovery. (shrink)

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released (...) DR9 and DR10 samples. Assuming a concordance Λ cold dark matter cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = at z = 0.32 and DV = at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = and H =. Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society. (shrink)

BackgroundStructured, systematic methods to formulate consensus recommendations, such as the Delphi process or nominal group technique, among others, provide the opportunity to harness the knowledge of experts to support clinical decision making in areas of uncertainty. They are widely used in biomedical research, in particular where disease characteristics or resource limitations mean that high-quality evidence generation is difficult. However, poor reporting of methods used to reach a consensus – for example, not clearly explaining the definition of consensus, or not stating (...) how consensus group panellists were selected – can potentially undermine confidence in this type of research and hinder reproducibility. Our objective is therefore to systematically develop a reporting guideline to help the biomedical research and clinical practice community describe the methods or techniques used to reach consensus in a complete, transparent, and consistent manner.MethodsThe ACCORD project will take place in five stages and follow the EQUATOR Network guidance for the development of reporting guidelines. In Stage 1, a multidisciplinary Steering Committee has been established to lead and coordinate the guideline development process. In Stage 2, a systematic literature review will identify evidence on the quality of the reporting of consensus methodology, to obtain potential items for a reporting checklist. In Stage 3, Delphi methodology will be used to reach consensus regarding the checklist items, first among the Steering Committee, and then among a broader Delphi panel comprising participants with a range of expertise, including patient representatives. In Stage 4, the reporting guideline will be finalised in a consensus meeting, along with the production of an Explanation and Elaboration document. In Stage 5, we plan to publish the reporting guideline and E&E document in open-access journals, supported by presentations at appropriate events. Dissemination of the reporting guideline, including a website linked to social media channels, is crucial for the document to be implemented in practice.DiscussionThe ACCORD reporting guideline will provide a set of minimum items that should be reported about methods used to achieve consensus, including approaches ranging from simple unstructured opinion gatherings to highly structured processes. (shrink)

Debate about deregulation has focused considerable attention on the pricing policies of public utilities. Much work has been done by economists on this subject, and in this book the results of that research are presented and made accessible to students of economics. The main subject is the policy to be followed by a regulated monopoly, but the analysis is broadened to take account of a fringe of competitive suppliers, making it relevant to electric utilities and local telephone companies in the (...) US, to PTT's in Europe, to the possible privatisatibn of telecommunications in Australia, and to the telecommunications structure in the UK where the dominant supplier has recently been privatised. The book gives a unified and simplified exposition of the modern theory of efficient pricing which is not available elsewhere. The theoretical discussion is supplemented by numerical simulation comparing Fully Distributed Cost Pricing, Ramsey Pricing, and Optimal Non-uniform Pricing. (shrink)

We defend, from a contractarian perspective, that the fair price of an insurance policy is the amount that the contracting parties agree when they are both equally uncertain about the insured event. Drawing on the approach developed by R. Sugden in _The Community of Advantage_, we answer two standard objections raised against contractarianism in the actuarial sciences: (1) people are not wise enough to assess their actuarial risks; (2) they are not rational enough to decide which insurance policy suits (...) them better. We show under which circumstances people can make fair actuarial agreements, without presupposing any objective risk or rationality benchmarks. (shrink)

In actuarial parlance, the price of an insurance policy is considered fair if customers bearing the same risk are charged the same price. The estimate of this fair amount hinges on the expected value obtained by weighting the different claims by their probability. We argue that, historically, this concept of actuarial fairness originates in an Aristotelian principle of justice in exchange (equality in risk). We will examine how this principle was formalized in the 16th century and shaped in (...) life insurance during the following two hundred years, in two different interpretations. The Domatian account of actuarial fairness relied on subjective uncertainty: An agreement on risk was fair if both parties were equally ignorant about the chances of an uncertain event. The objectivist version grounded any agreement on an objective risk estimate drawn from a mortality table. We will show how the objectivist approach collapsed in the market for life annuities during the 18th century, leaving open the question of why we still speak of actuarial fairness as if it were an objective expected value. (shrink)

Since the attack on the World Trade Center in New York, and on the Pentagon in the United States, concerns over security issues have been at an all-time high in this country. Both state and federal governments continue to discuss legislation on these issues amid much controversy. One key concern of both employers and employees is the extent that employers, espousing a "need to know" mentality, continue to expand their capability and implementation of surveillance of employees in the workplace. With (...) the technology typically growing faster than the speed of legislation, protective or permissive, the management and legal issues involved in electronic monitoring of employee communications in the workplace, are and well should be on the agenda for discussion of every management and legal team in American business today. Companies have a legitimate right to protect their trade secrets from disclosure by disgruntled employees. Similarly, companies also have a duty to protect their good names and reputations from unauthorized employee communications with outside parties, and even other employees, that may damage them. It is also a prime duty of management to ensure, in their direction of their workforces, that the employees execute their responsibilities by working full time on their stated objectives. In this regard, any management that fails to oversee its workforce to ensure that employees are not expending valuable company time, for which they are being compensated, on personal business, including unauthorized communications, is remiss in its responsibilities to its shareholders. The company may see a reduction of the price of its shares in the marketplace if it does not protect the economic interests of its shareholders. (shrink)

Gershom Scholem wrote his famous article, “Redemption through sin”, in 1937, and J.L. Talmon gained the inspiration for his first book, The Origins of Totalitarian Democracy, in the years 1937–1938 at the time when the Moscow trials revealed to the world the bitter reality of what was happening in the Soviet Union. Scholem and Talmon were contemporaries and witnesses of the transformation of communism in the Soviet Union from a vision of egalitarian and universal redemption into a bureaucratic and nationalistic (...) despotism. The major scholar of the history of religious Messianism and the major scholar of the history of secular Messianism both widened the scope of their investigations—the first extending them into the history of Sabbataianism and the second into the French Revolution—and both reached a similar conclusion: both recognized, as Scholem put it, “the profound truth relating to the dialectics of history … of the historical process whereby the fulfilment of one political process leads to the manifestation of its opposite. In the realization of one thing its opposite is revealed”. The two great Israeli historians of ideas plumbed the depths of one of the most fascinating and at the same time tragic manifestations of la condition humaine: the human challenge of bringing the heavenly city down to the vale of tears, and the price that men have to pay for their Messianic passion. (shrink)

In nine lively essays, bioethicist J. David Velleman challenges the prevailing consensus about assisted suicide and reproductive technology, articulating an original approach to the ethics of creating and ending human lives. He argues that assistance in dying is appropriate only at the point where talk of suicide is not, and he raises moral objections to anonymous donor conception. In their place, Velleman champions a morality of valuing personhood over happiness in making end-of-life decisions, and respecting the personhood of future (...) children in making decisions about procreation. These controversial views are defended with philosophical rigor while remaining accessible to the general reader. Written over Velleman's 30 years of undergraduate teaching in bioethics, the essays have never before been collected and made available to a non-academic audience. They will open new lines of debate on issues of intense public interest."--Publisher's website. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Buddhist-Christian Studies 20 (2000) 321-323 [Access article in PDF] Frederick J. Streng Book Award David Loy Interview The 1999 winner of the Frederick J. Streng Book Award is David R. Loy, professor on the Faculty of International Studies at Bunkyo University in Chigasaki, Japan. Professor Loy received the award for his book, Lack and Transcendence: The Problem of Death and Life in Psychotherapy, Existentialism, and Buddhism, published (...) by Humanities Press (New Jersey) in 1996. The book places Western patterns of thought developed in tandem with Christian ideas into dialogic contact with Buddhism. It is thus a very Buddhist book, but a signal contribution to the practice of Buddhist-Christian dialogue. Buddhist-Christian Studies asked David about his writing of the volume.Buddhist-Christian Studies: Why did you write this book?David Loy: It was the product of an existential crisis, both intellectual and personal. My father, who had always been healthy and full of life, suddenly became ill with pancreatic cancer. Then my Zen teacher Yamada Koun had a bad fall that led to his death a year later. Not long before that my relationship with him and the Sanbo Kyodan had become somewhat problematic. This threatened my 'spiritual ground'. Finally, I was without a job. All this gave me plenty of time not only to sit intensively but also to read widely everything I could find on death and related issues.Did you think that sitting and studying would lead to a book?I didn't know. I could feel something gestating. I realized something was needed in this area. I was (and still am) very impressed by the last two books of Ernest Becker, but despite their brilliance his notion of death-denial is a little off-center from a Buddhist perspective. Fear of death projects our problem into the future, while the groundlessness of our sense-of-self accounts better for our sense-of-lack right here and now.What was the final trigger for doing the book?Another Zen teacher suggested that I try to write a Zen teisho [sermon or talk]. I sat down but after a few lines so many other thoughts began to bubble up that I couldn't write them down fast enough. There was no obvious or immediate logical connection among them, but they kept coming. This went on for about two, almost non-stop, days. After that the thoughts slowed down. I read over the notes I'd written, which led to more ideas, and then I began to perceive their relationship. After five days or so I had a detailed outline for the book, and the real work began. [End Page 321]What kind of response to the book, both positive and negative, have you received?There have not been many reviews, but they have generally been positive. It's not an easy book to evaluate: it brings together many different thinkers and traditions in order to address many different issues. In the process it attempts what is almost a grand synthesis of Buddhism, existentialism, and psychotherapy around the notion of our 'sense of lack', which I argue motivates us all. This involves close readings of Freud, Heidegger, Nietzsche, Nagarjuna, and many others. Unfortunately, the print is small and not easy to read, the cover is ugly, and the price is too high. For all these reasons readers have my sympathies! But there are some readers for whom the book really 'clicks'. I'm pleased that it seems to work on the existential as well as the intellectual level, for such people.After several years of reflection, would you write it any differently today?Yes, probably. The first thing I would do is take out the last chapter "Transcendence East and West," which was an afterthought and doesn't really fit in very well. As published, the chapter takes the concept of 'lack' into a new dimension which needs to be worked out much more carefully than I did in the book. It argues that, in place of the usual East-West dichotomy, it is more insightful to view South Asian Indian- influenced cultures as in some ways... (shrink)

At any given time, a subject has a multiplicity of conscious experiences. A subject might simultaneously have visual experiences of a red book and a green tree, auditory experiences of birds singing, bodily sensations of a faint hunger and a sharp pain in the shoulder, the emotional experience of a certain melancholy, while having a stream of conscious thoughts about the nature of reality. These experiences are distinct from each other: a subject could experience the red book without the singing (...) birds, and could experience the singing birds without the red book. But at the same time, the experiences seem to be tied together in a deep way. They seem to be unified, by being aspects of a single encompassing state of consciousness. (shrink)

Scientific naturalism is a metaphysical doctrine, a view about what there is, or what we ought to believe that there is. It maintains that natural science should be our guide in matters metaphysical: the ontology we should accept is the ontology that turns out to be required by science. Quine is often regarded as the doyen of scientific naturalists, though the supporting cast includes such giants as David Lewis and J. J. C. Smart.

Bornstein, David. The Price of a Dream: The Idea of the Grameen Bank and the Idea That Is Helping the Poor to Change Their Lives. New York: Simon & Schuster, 1996. 370 pp. $25.00 (cloth).

In this seminal work, acclaimed philosopher Bernhard Waldenfels deals with the problem of the nature of order after the “shattering of the world,” and the loss of the idea of a universal or fundamental order._ _ Order in the Twilight__ unites phenomenological methodology with recent work on the theory of order, normativity, and dialogue, as well as structuralism and Gestalt theory. Philosophically stringent, it expresses a more optimistic attitude than much modern philosophy, especially deconstruction._ Waldenfels passes the question of order (...) through numerous defining aspects, and concludes that there is not one global order, but rather various conflicting domains of order. Whenever the boundary of a vital or experiential domain is crossed, a discourse speaks at the boundary, not about it, and across a threshold without abolishing it. The rest is rationalization, i.e., an attempt to find a place in the respective order for what is to-be-ordered. But why, the author concludes, should a theory be more unambiguous than reality? _ Order in the Twilight__ is an important book at this time, because it may help lift the humanities out of the skeptical, relativistic disarray in which they have been embroiled in recent decades. Waldenfels does not attempt to dictate what reality should be; rather, he is open to any valid evidences. His book offers a solid footing to the human and social sciences as they seek to escape from deconstructive irrationalism. (shrink)

This interdisciplinary and systematic collection of essays explores pragmatism in relation to three key episodes in American culture: Progressivism, Positivism, and Postmodernism.

The future of higher education is in question as universities struggle to remain relevant to the present and future needs of society. The context in which learning occurs is rapidly changing and those engaged and interested in the place and position of university education need to figure out to adapt. This book embodies a vision for higher education where graduate attributes and proficiencies are at the core of the academic project, where degree programs move beyond disciplinary content and where students (...) are encouraged to be Citizen Scholars. Through a series of cross-disciplinary and contextual cases, the contributors to this book articulate how this vision can be achieved in our pedagogical environments, future proofing higher education. (shrink)

This book is the result of a conference that addressed two pressing issues for christianity in the modern world.

[In Meaning in Mind, edited by Barry Loewer and Georges Rey. Oxford: Basil Black- well, 1991, 165.

David and Mary Norton present the definitive scholarly edition of one of the greatest philosophical works ever written. This second volume begins with their 'Historical Account' of the Treatise, an account that runs from the beginnings of the work to the period immediately following Hume's death in 1776, followed by an account of the Nortons' editorial procedures and policies and a record of the differences between the first-edition text of the Treatise and the critical text that follows. The volume (...) continues with an extensive set of 'Editors' Annotations', intended to illuminate Hume's texts; a four-part bibliography of materials cited in both volumes; and a comprehensive index. (shrink)

It has been 35 years since the publicationMelzack and Wall's Gate Control Theory whichhypothesized that nociceptive information wassubject to dynamic regulation by mechanismslocated in the spinal cord dorsal horn thatcould ultimately lead to hyperalgesic orhypoalgesic states. This paper examines GateControl Theory in light of our currentunderstanding of the neuroanatomical,neurophysiological and neurochemical substratesof nociception and antinociception. Despiteits initial controversies, no one has proposeda more comprehensive overall theory of painmodulation or has successfully refuted most ofthe basic tenets of this theory.

Intended to complement the reading of Hume's own works in a philosophy course, this is a collection of recent journal articles on Hume's thought and relevant philosophical problems. Included are essays by Flew, Price, Strawson, Broad, Gasking, Penelhum, and Popper. This book should prove useful in making readily available discussions relating Hume's philosophy to contemporary problems.—R. J. W.

The years from 1918 to 1945 remain central to European History. It was a breath-taking time during which the very best and very worst attributes of Mankind were on display. In the euphoria of peace which followed the end of the First World War, the Baltic States emerged as independent forces on the world stage, participating in thrilling experiments in national and transnational governance. Later, following economic collapse and in the face of rising totalitarianism among even Europe’s most cultured nations, (...) Baltic communities succumbed to nationalism too. During wartime, Baltic peoples became both victims and, sometimes, victimisers. Ultimately their victimhood lasted until the end of the Cold War, yielding consequences still discernible at the start of the twenty first century. Taking the period 1918 to 1945 as pivotal, this collection of essays examines some of the key themes in Baltic History as they are emerging today. These include appreciations of identity, autonomy and the rights of national minorities; the everyday and social foundations of international security; and the importance of historical memory to popular and political identities. (shrink)