Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Over recent years, the research community has been increasingly using preprint servers to share manuscripts that are not yet peer-reviewed. Even if it enables quick dissemination of research findings, this practice raises several challenges in publication ethics and integrity. In particular, preprints have become an important source of information for stakeholders interested in COVID19 research developments, including traditional media, social media, and policy makers. Despite caveats about their nature, many users can still confuse pre-prints with peer-reviewed manuscripts. If unconfirmed but (...) already widely shared first-draft results later prove wrong or misinterpreted, it can be very difficult to “unlearn” what we thought was true. Complexity further increases if unconfirmed findings have been used to inform guidelines. To help achieve a balance between early access to research findings and its negative consequences, we formulated five recommendations: (a) consensus should be sought on a term clearer than ‘pre-print’, such as ‘Unrefereed manuscript’, “Manuscript awaiting peer review” or ‘’Non-reviewed manuscript”; (b) Caveats about unrefereed manuscripts should be prominent on their first page, and each page should include a red watermark stating ‘Caution—Not Peer Reviewed’; (c) pre-print authors should certify that their manuscript will be submitted to a peer-review journal, and should regularly update the manuscript status; (d) high level consultations should be convened, to formulate clear principles and policies for the publication and dissemination of non-peer reviewed research results; (e) in the longer term, an international initiative to certify servers that comply with good practices could be envisaged. (shrink)

_The first part called the Preamble tackles: (a) the issues of silence and speech, and life and disease; (b) whether we need to know some or all of the truth, and how are exact science and philosophical reason related; (c) the phenomenon of Why, How, and What; (d) how are mind and brain related; (e) what is robust eclecticism, empirical/scientific enquiry, replicability/refutability, and the role of diagnosis and medical model in psychiatry; (f) bioethics and the four principles of beneficence, non-malfeasance, (...) autonomy, and justice; (g) the four concepts of disease, illness, sickness, and disorder; how confusion is confounded by these concepts but clarity is imperative if we want to make sense out of them; and how psychiatry is an interim medical discipline. The second part called The Issues deals with: (a) the concepts of nature and nurture; the biological and the psychosocial; and psychiatric disease and brain pathophysiology; (b) biology, Freud and the reinvention of psychiatry; (c) critics of psychiatry, mind-body problem and paradigm shifts in psychiatry; (d) the biological, the psychoanalytic, the psychosocial and the cognitive; (e) the issues of clarity, reductionism, and integration; (f) what are the fool-proof criteria, which are false leads, and what is the need for questioning assumptions in psychiatry. The third part is called Psychiatric Disorder, Psychiatric Ethics, and Psychiatry Connected Disciplines. It includes topics like (a) psychiatric disorder, mental health, and mental phenomena; (b) issues in psychiatric ethics; (c) social psychiatry, liaison psychiatry, psychosomatic medicine, forensic psychiatry, and neuropsychiatry. The fourth part is called Antipsychiatry, Blunting Creativity, etc. It includes topics like (a) antipsychiatry revisited; (b) basic arguments of antipsychiatry, Szasz, etc.; (c) psychiatric classification and value judgment; (d) conformity, labeling, and blunting creativity. The fifth part is called The Role of Philosophy, Religion, and Spirituality in Psychiatry. It includes topics like (a) relevance of philosophy to psychiatry; (b) psychiatry, religion, spirituality, and culture; (c) ancient Indian concepts and contemporary psychiatry; (d) Indian holism and Western reductionism; (e) science, humanism, and the nomothetic-idiographic orientation. The last part, called Final Goal, talks of the need for a grand unified theory. The whole discussion is put in the form of refutable points._. (shrink)

Inside What Would Plato Do?, you'll find the basics of philosophy, written in an easy, digestible way we can all understand, along with questions to help you apply these important theories to your own life. So, after you've learned about a philosophical concept, you'll then be challenged to test yourself and see how the results can impact your daily life. For instance, after learning about Kant's theory of morality and the importance of intention you're challenged with questions like: Can good (...) people do bad things? Was there a time when you intended to do something helpful that ended up being hurtful? Does that make you a good person (because you intended to do good) or a bad person (because the results were bad)? What Would Plato Do? will not only help you better understand some of the greatest thinkers ever but will also help you think of the world around you in a whole new way! (shrink)

In a previous paper by Pollock and Singh, it was proven that the total entropy of de Sitter space-time is equal to zero in the spatially flat case K=0. This result derives from the fundamental property of classical thermodynamics that temperature and volume are not necessarily independent variables in curved space-time, and can be shown to hold for all three spatial curvatures K=0,±1. Here, we extend this approach to Schwarzschild space-time, by constructing a non-vacuum interior space with line element (...) ds 2=e2λ(r) dt 2−e−2λ(r) dr 2−r 2(dθ 2+sin2 θdϕ 2), where $\mathrm{e}^{2{\lambda }(r)}=-\frac{1}{2}(1-\frac{r^{2}}{R_{0}^{2}})$ , which matches onto the vacuum exterior Schwarzschild metric in such a way that e2λ and d(e2λ )/dr are both continuous at the Schwarzschild radius R 0=2M. Then we show that the volume entropy is equal to A/4, where $A\equiv 4\pi R_{0}^{2}$ is the area of the apparent horizon, as found by Hawking. (shrink)

To date the teaching of business ethics has been examined from the descriptive, prescriptive, and analytical perspectives. The descriptive perspective has reviewed the existence of ethics courses (e.g., Schoenfeldtet al., 1991; Bassiry, 1990; Mahoney, 1990; Singh, 1989), their historical development (e.g., Sims and Sims, 1991), and the format and syllabi of ethics courses (e.g., Hoffman and Moore, 1982). Alternatively, the prescriptive literature has centred on the pedagogical issues of teaching ethics (e.g., Hunt and Bullis, 1991; Strong and Hoffman, 1990; (...) Reeves, 1990; Castro, 1989; George, 1987; Golenet al., 1985) and in providing recommendations for teachers of business ethics (e.g., Nappi, 1990; Hosmer and Steneck, 1989). From the analytical perspective judgments have been made as to whether courses in ethics are in fact effective in achieving value and attitudinal modifications in students (e.g., Loeb, 1991; Weber, 1990; Wynd and Mager, 1989; Pamental, 1989; Martin, 1982; Purcell, 1977). The evidence to date suggests that courses can be a means of achieving ethical awareness and sensitivity in students although it should be recognized that significant objections to the teaching of business ethics do exist and greatly inhibit their successful introduction. This paper addresses a number of the common objections to the teaching of business ethics that must be overcome if ethical programs are to continue in the future, and concludes with recommendations to facilitate the establishment of ethical training in an academic context. (shrink)

Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also to mediate immune tolerance. We propose that tolerogenic and immunogenic responses of LCs are directed by signaling from the epidermis and involve counter‐acting gene circuits that are coupled to a core maturation gene module. We base our analysis on recent genetic and genomic findings facilitating the understanding of the molecular mechanisms controlling these divergent immune functions. Comparing gene regulatory network (GRN) analyses of various types (...) of dendritic cells (DCs) including LCs we integrate signaling‐dependent (TGFβ, EpCAM, β‐Catenin) and transcription factor (IRF4, IRF1, NFκB) regulated gene circuits that appear to orchestrate the distinctive LC functional states. Our model proposes, that while epidermal signaling in the steady‐state promotes LC tolerogenic function, the disruption of cell‐cell contacts coupled with inflammatory signaling induces LC immunogenic programing. The conceptual framework emphasizes the sensing of discrete epidermal and inflammatory cues by resident LCs in dictating their genomic programing and cell state dynamics. (shrink)

D E Cooper; Is Language Learned?1, Journal of Philosophy of Education, Volume 9, Issue 1, 30 May 2006, Pages 93–104, https://doi.org/10.1111/j.1467-9752.1975.tb.

D E Cooper; Is Language Learned?1, Journal of Philosophy of Education, Volume 9, Issue 1, 30 May 2006, Pages 93–104, https://doi.org/10.1111/j.1467-9752.1975.tb.

People with mild to moderate intellectual or multiple disabilities may have serious difficulties in accessing leisure events, managing communication exchanges with distant partners, and performing functional daily activities. Recently, efforts were made to develop and assess technology-aided programs aimed at supporting people in all three areas. This study assessed a new technology-aided program aimed at helping four participants with intellectual and multiple disabilities in the aforementioned areas. The program, which was implemented following a non-concurrent multiple baseline across participants design, relied (...) on the use of a smartphone or tablet connected via Bluetooth to a two-switch device. This device served to select leisure and communication events and to control the smartphone or tablet’s delivery of step instructions for the activities scheduled. Data showed that during the baseline phase, three participants failed in each of the areas while one participant managed to access a few leisure events. During the intervention phase, all participants managed to independently access leisure events, make telephone calls, and carry out activities. These results suggest that the program might be a useful tool for helping people with intellectual and multiple disabilities improve their condition in basic areas of daily life. (shrink)

Measuring event-related potentials (ERPs) has been fundamental to our understanding of how language is encoded in the brain. One particular ERP response, the N400 response, has been especially influential as an index of lexical and semantic processing. However, there remains a lack of consensus on the interpretation of this component. Resolving this issue has important consequences for neural models of language comprehension. Here we show that evidence bearing on where the N400 response is generated provides key insights into what it (...) reflects. A neuroanatomical model of semantic processing is used as a guide to interpret the pattern of activated regions in functional MRI, magnetoencephalography and intracranial recordings that are associated with contextual semantic manipulations that lead to N400 effects. (shrink)

Philosophers of technology are not playing the public role that our own theoretical perspectives motivate us to take. A great variety of theories and perspectives within philosophy of technology, including those of Marcuse, Feenberg, Borgmann, Ihde, Michelfelder, Bush, Winner, Latour, and Verbeek, either support or directly call for various sorts of intervention—a call that we have failed to heed adequately. Barriers to such intervention are discussed, and three proposals for reform are advanced: post-publication peer-reviewed reprinting of public philosophy, increased emphasis (...) on true open access publication, and increased efforts to publicize and adapt traditional academic research. (shrink)

Our concern in this paper lies with a common argument from racial discrimination to realism about races: some people are discriminated against for being members of a particular race (i.e., racial discrimination exists), so some people must be members of that race (i.e., races exist). Error theorists have long responded that we can explain racial discrimination in terms of racial attitudes alone, so we need not explain it in terms of race itself. But to date there has been little detailed (...) discussion of whether it is better to explain racial discrimination in terms of race or in terms of racial attitudes alone. Our goal is to offer a novel and detailed argument in defense of explaining racial discrimination in terms of racial attitudes alone, by attending to the neglected phenomenon of misperception discrimination, which involves differential treatment due to misperceived race. We argue that the discriminatory action in misperception cases must be explained in the same way as cases where (according to the realist) the victim’s race is accurately perceived. Thus, the victim’s actual race cannot provide the best explanation. The main upshot of our argument is that explanatory arguments from racial discrimination to realism about race fail. (shrink)

I welcome Mr Kennedy's general approach, but query whether the concept of consumerism is so closely applicable to medical care as he maintains. However, in particular aspects, especially the handling of complaints, his criticisms echo those made by the Patients Association. Finally, I detect some ground for hope in the more enlightened attitude creeping in to the eduction of the medical student.

There is a common view in medical ethics that the patient's right to be informed entails, as well, a correlative right not to be informed, i.e., to waive one's right to information. This paper argues, from a consideration of the concept of autonomy as the foundation for rights, that there can be no such ‘right’ to refuse relevant information, and that the claims for such a right are inconsistent with both deontological and utilitarian ethics. Further, the right to be informed (...) is shown to be a mandatory right (though not a welfare right); persons are thus seen to have both a right and a duty to be informed. Finally, the consequences of this view are addressed: since the way in which we conceptualize our problems tends to determine the actions we take to resolve them, it is important properly to conceptualize patients' requests not to be informed. There may be many reasons for acting in accord with such a request, but it is a mistake to conceptualize one's act as ‘respecting a right possessed by persons’. Keywords: medical ethics, informed consent, autonomy, information-waivers, rights, obligations CiteULike Connotea Del.icio.us What's this? (shrink)

Causal theories of content, a popular family of approaches to defining the content of mental states, commonly run afoul of two related and serious problems that prevent them from providing an adequate theory of mental content—the misrepresentation problem and the disjunction problem. In this paper, I present a causal theory of content, built on information theoretic tools, that solves these problems and provides a viable model of mental content. This is the greatest surprise reduction theory of content, which identifies the (...) content of a signal as the event the surprisal of which is most reduced by that signal. Conceptually, this amounts to the claim that the content of a signal is the event the probability of which has increased by the largest proportion, or the event that the signal makes the most less surprising to us. I develop the greatest surprise reduction theory of content in four stages. First, I introduce the general project of causal theories of content, and the challenges presented to this project by the misrepresentation and disjunction problems. Next, I review two recent and prominent causal theories of content and demonstrate the serious challenges faced by these approaches, both clarifying the need for a solution to the misrepresentation and disjunction problems and providing a conceptual background for the greatest surprise reduction theory. Then, I develop the greatest surprise reduction theory of content, demonstrate its ability to resolve the misrepresentation and disjunction problems, and explore some additional applications it may have. Finally, I conclude with a discussion of a particularly difficult challenge that remains to be addressed—the partition problem—and sketch a path to a potential solution. (shrink)

(2001). Atomists, Liberals and Civic Republicans: Taylor on the Ontology of Citizenship. Australasian Journal of Philosophy: Vol. 79, No. 4, pp. 465-478.

Infinite time Turing machines with only one tape are in many respects fully as powerful as their multi-tape cousins. In particular, the two models of machine give rise to the same class of decidable sets, the same degree structure and, at least for partial functions f : ℝ → ℕ, the same class of computable functions. Nevertheless, there are infinite time computable functions f : ℝ → ℝ that are not one-tape computable, and so the two models of infinitary computation (...) are not equivalent. Surprisingly, the class of one-tape computable functions is not closed under composition; but closing it under composition yields the full class of all infinite time computable functions. Finally, every ordinal that is clockable by an infinite time Turing machine is clockable by a one-tape machine, except certain isolated ordinals that end gaps in the clockable ordinals. (shrink)