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)

R&D collaborations between industry, government, civil society, and research ) have recently gained attention from R&D theorists and practitioners. In aiming to come to grips with their complexity, past models have generally taken a stakeholder-analytical approach based on stakeholder types. Yet stakeholder types are difficult to operationalise. We therefore argue that a processual model is more suited for studying the interaction in QHCs because it eschews matters of titles and identities. We develop such a model in which the QHC is (...) represented as a process of generating four types of value: research value, market value, political value, and societal value. We then apply this processual model in analysing real-life cases of friction in QHCs. Friction is seen, not as an interpersonal clash, but as a discrepancy between two or more value-creation processes that compete for limited resources. (shrink)

Internet-based health research is increasing, and often offers financial incentives but fraudulent behavior by participants can result. Specifically, eligible or ineligible individuals may enter the study multiple times and receive undeserved financial compensation. We review past experiences and approaches to this problem and propose several new strategies. Researchers can detect and prevent Internet research fraud in four broad ways: through the questionnaire/instrument ; through participants' non-questionnaire data and seeking external validation through computer information,, and 4) through study design. These approaches (...) each have pros and cons, and raise ethical, legal, and logistical questions, given that ethical tensions can emerge between preserving the integrity of research vs. protecting the privacy and confidentiality of study respondents. While past discussions concerning the ethics of online research have tended to focus on the participants' ability to trust the researchers, needs now arise to examine researchers' abilities to trust the participants. This analysis has several critical implications for future practice, policy, and research. (shrink)

Once we have accepted that the Ciris stems from neither Virgil nor Gallus, but was written by a post-Virgilian poetaster, the obvious task for us is to try and formulate some more specific idea of the date of the poem. I think that it has been sufficiently proved that the Ciris is not only post-Virgilian, but post-Ovidian in origin, including as it does unquestionable imitations of that author. But this, to date, is really as far as we have got. It (...) is the purpose of this paper to put forward the thesis that the author of the Ciris lived late enough to know and be influenced by Statius and other poets of the later first century A.D. Now of course any theory that the Ciris knew and used Statius and other Silver poets is rendered highly unlikely if it can be maintained that Suetonius considered it, with the other minora, a genuine Virgilian work. And so we are brought back again to the famous list in the Donatan Life: deinde Catalepton et Priapea et Epigrammata et Diras, item Cirim et Culicem, cum esset annorum XXVI. cuius materia talis est. pastor fatigatur aestu; cum sub arbore condormisset et serpens ad eum proreperet, e palude culex provolavit atque inter duo tempora aculeum fixit pastori. at ille continuo culicem contrivit et serpentem interemit ac sepulchrum culici statuit et distichon fecit. (shrink)

Once we have accepted that theCirisstems from neither Virgil nor Gallus, but was written by a post-Virgilian poetaster, the obvious task for us is to try and formulate some more specific idea of the date of the poem. I think that it has been sufficiently proved that theCirisis not only post-Virgilian, but post-Ovidian in origin, including as it does unquestionable imitations of that author. But this, to date, is really as far as we have got. It is the purpose of (...) this paper to put forward the thesis that the author of theCirislived late enough to know and be influenced by Statius and other poets of the later first century A.D.Now of course any theory that theCirisknew and used Statius and other Silver poets is rendered highly unlikely if it can be maintained that Suetonius considered it, with the otherminora, a genuine Virgilian work. And so we are brought back again to the famous list in the DonatanLife:deinde Catalepton et Priapea et Epigrammata et Diras, item Cirim et Culicem, cum esset annorum XXVI. cuius materia talis est. pastor fatigatur aestu; cum sub arbore condormisset et serpens ad eum proreperet, e palude culex provolavit atque inter duo tempora aculeum fixit pastori. at ille continuo culicem contrivit et serpentem interemit ac sepulchrum culici statuit et distichon fecit. (shrink)

The volume presents essays on the philosophical explanation of the relationship between body and soul in antiquity from the Presocratics to Galen. The title of the volume alludes to a phrase found in Plato, Aristotle and Plotinus, referring to aspects of living behaviour involving both body and soul, and is a commonplace in ancient philosophy, dealt with in very different ways by different authors.

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity with rice (...) of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7. (shrink)

Coastal ecosystems are increasingly dominated by humans. Consequently, the human dimensions of sustainability science have become an integral part of emerging coastal governance and management practices. But if we are to avoid the harsh lessons of land management, coastal decision makers must recognize that humans are one of the more coastally dependent species in the biosphere. Management responses must therefore confront both the temporal urgency and the very real compromises and sacrifices that will be necessary to achieve a sustainable coastal (...) ecosystem, one that is economically feasible, socially just, and ecologically sound. (shrink)

Two rotational bands have been identified and characterized in the proton-magic N = Z + 1 nucleus Ni-57. These bands complete the systematics of well-and superdeformed rotational bands in the light nickel isotopes starting from doubly magic Ni-56 to Ni-60. High-spin states in Ni-57 have been produced in the fusion-evaporation reaction Si-28(S-32, 2p1n)Ni-57 and studied with the gamma-ray detection array GAMMASPHERE operated in conjunction with detectors for evaporated light charged particles and neutrons. The features of the rotational bands in Ni-57 (...) are compared to those of neighbouring isotopes and interpreted by means of configuration-dependent cranked Nilsson-Strutinsky calculations. The two observed high-spin bands are considered signature partners and assigned to configurations with one 1g(9/2) proton and one 1g(9/2) neutron, resulting in an unambiguous understanding of the energetically favoured signature alpha = -1/2 band but a somewhat less satisfactory description of the signature alpha = +1/2 band. (shrink)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

In two studies, we explored the frequency and phenomenology of musical imagery. Study 1 used retrospective reports of musical imagery to assess the contribution of individual differences to imagery characteristics. Study 2 used an experience sampling design to assess the phenomenology of musical imagery over the course of one week in a sample of musicians and non-musicians. Both studies found episodes of musical imagery to be common and positive: people rarely wanted such experiences to end and often heard music that (...) was personally meaningful. Several variables predicted musical imagery, including personality, musical preferences, and positive mood. Musicians tended to hear musical imagery more often, but they reported less frequent episodes of deliberately-generated imagery. Taken together, the present research provides new insights into individual differences in musical imagery, and it supports the emerging view that such experiences are common, positive, and more voluntary than previously recognized. (shrink)

One of the central issue of developmental biology concerns the molecular mechanisms whereby a multipotent cell gives rise to distinct differentiated progeny. Differences between specialised cell types reflect variations in their patterns of gene expression. The regulation of transcription initiation is an important control point for gene expression and it is, therefore, not surprising that transcription factors play a pivotal role in mammalian development and differentiation.Haemopoiesis offers a uniquely tractable system for the study of lineage commitment and differentiation. The importance (...) of transcription factor in the normal regulation of haemopoiesis is underlined by the frequency with which transcription factors are targeted by leukaemogenic mutations. Studies of the function and regulation of haemopoietic transcription factors, especially those expressed in lineage‐restricted patterns, should greatly increase our understanding of the molecular control of haemopoiesis. In this review we have focused on insights provided by recent studies of the GATA and SCL proteins. (shrink)

The 2015 Paris Agreement set a global warming limit of 2°C above preindustrial levels. Corporations play an important role in achieving this objective, and methods have recently been developed to map global climate targets to specific industries, and individual corporations within those industries. In this article, we assess whether Sustainability ratings capture corporate performance in meeting the 2°C target. We analyze nine rating schemes used by investors and three commonly used in academic studies. Most rating schemes do consider corporate greenhouse (...) gas emissions in their analysis, whereas only a minority scale emissions by factors that have the potential to allow benchmarking against science-based targets. None take the final step of mapping climate indicators against the 2°C target. Furthermore, we find a lack of consistency in the climate change ratings of the databases used in academic studies. These results are concerning in the context of being able to meet global climate change goals. (shrink)

Initial responses to questionnaires used to assess participants' understanding of informed consent for malaria vaccine trials conducted in the United States and Mali were tallied. Total scores were analyzed by age, sex, literacy (if known), and location. Ninety-two percent (92%) of answers by United States participants and 85% of answers by Malian participants were correct. Questions more likely to be answered incorrectly in Mali related to risk, and to the type of vaccine. For adult participants, independent predictors of higher scores (...) were younger age and female sex in the United States, and male sex in Mali. Scores in the United States were higher than in Mali (P = 0.005). Despite this difference participants at both sites were well informed overall. Although interpretation must be qualified because questionnaires were not intended as research tools and were not standardized among sites, these results do not support concerns about systematic low understanding among research participants in developing versus developed countries. (shrink)

Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the patient (...) reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere. (shrink)

Integrating concepts of maintenance and of origins is essential to explaining biological diversity. The unified theory of evolution attempts to find a common theme linking production rules inherent in biological systems, explaining the origin of biological order as a manifestation of the flow of energy and the flow of information on various spatial and temporal scales, with the recognition that natural selection is an evolutionarily relevant process. Biological systems persist in space and time by transfor ming energy from one state (...) to another in a manner that generates structures which allows the system to continue to persist. Two classes of energetic transformations allow this; heat-generating transformations, resulting in a net loss of energy from the system, and conservative transformations, changing unusable energy into states that can be stored and used subsequently. All conservative transformations in biological systems are coupled with heat-generating transformations; hence, inherent biological production, or genealogical proesses, is positively entropic. There is a self-organizing phenomenology common to genealogical phenomena, which imparts an arrow of time to biological systems. Natural selection, which by itself is time-reversible, contributes to the organization of the self-organized genealogical trajectories. The interplay of genealogical (diversity-promoting) and selective (diversity-limiting) processes produces biological order to which the primary contribution is genealogical history. Dynamic changes occuring on times scales shorter than speciation rates are microevolutionary; those occuring on time scales longer than speciation rates are macroevolutionary. Macroevolutionary processes are neither redicible to, nor autonomous from, microevolutionary processes. (shrink)

Endosperm is emerging as a system for investigating the genetic control of wall placement and deposition in plant development. Development of endosperm progresses in distinct stages from a wall‐less syncytial stage to a cellular stage that is entirely typical of plant meristems where the division plane is predicted by a preprophase band of microtubules (PPB) and cytokinesis is completed by formation of a cell plate in association with a phragmoplast. Four developmentally different types of walls, each associated with a different (...) microtubule system, are sequentially produced: (1) free growing walls deposited in the absence of mitosis and phragmoplasts; (2) walls guided by cytoplasmic phragmoplasts formed adventitiously in the absence of mitosis; (3) walls formed by interzonal phragmoplasts in a cell cycle that lacks PPBs; and (4) wall deposition driven by interzonal phragmoplasts in a cycle that includes PPBs. We are using methods of differential screening to isolate cDNA clones corresponding in temporal and spatial pattern to the types of wall development, and are studying mutants for clues to the genetic controls of wall development. (shrink)

High-spin states have been studied in Pr-135(59), populated through the Cd-116(Na-23,4n) reaction at 115 MeV, using the Gammasphere gamma-ray spectrometer. The negative-parity yrast band has been significantly extended to spin similar to 45 (h) over bar and excitation energy 21.5 MeV, showing evidence for several rotational alignments. The positive-parity yrast band of Ce-135(58), populated through the p4n channel of this reaction, was also populated to spin similar to 38 (h) over bar and excitation energy 18 MeV. Cranking calculations indicate that (...) these nuclei are soft with respect to the triaxiality parameter gamma and that several competing nuclear shapes occur at high spin. (shrink)

Subjects and Simulations presents essays focused on suffering and sublimity, representation and subjectivity, and the relation of truth and appearance through engagement with the legacies of Jean Baudrillard and Philippe Lacoue-Labarthe.

This book is a collection of secondary essays on America's most important philosophic thinkers—statesmen, judges, writers, educators, and activists—from the colonial period to the present. Each essay is a comprehensive introduction to the thought of a noted American on the fundamental meaning of the American regime.

Esta es una introducción al volumen especial de Empedocles: European Journal for the Philosophy of Communication enfocada en estudios latinoamericanos. Los trabajos que a continuación se presentan forman parte de una selección minuciosa llevada a cabo a propósito de varias conversaciones sobre Latinoamérica llevadas a cabo durante el último año. Los artículos en cuestión recorren transversalmente diversas áreas del pensamiento latinoamericano en la actualidad, particularmente las relacionadas con la filosofía, el arte, la literatura y los estudios visuales. Del mismo modo, (...) proponen lecturas alternativas de la realidad latinoamericana atendiendo a su autenticidad, su contexto y a la forma en la cual se interpretan y critican, implícita y explícitamente, categorías tradicionales como representación, poder, modernidad o género entre otras. (shrink)

This paper argues that professionals who make boundary-related decisions should be guided by relationship-based practice. In our roles as service users and professionals, drawing from our lived experiences of professional relationships, we argue we need to move away from distance-based practice. This includes understanding the boundary stories and narratives that exist for all of us – including the people we support, other professionals, as well as the organisations and systems within which we work. When we are dealing with professional boundary (...) issues, we should centre relationship-building skills that are central to many other aspects of our work. Skills that foster relationships at all levels – between professionals, service users, and services – need to be revalued. Our final recommendation is to create, develop, and foster safer spaces within and outside of organisations, as well as inter-professionally, for the discussion and exploration of boundary-related issues and practice. We are interested in hearing from those with experiences of being marginalised by boundaries so that they can inform a reshaping of our collective ideas around boundary related practices. To foster relationship-based practices in organisations, we have outlined several recommendations here; however, we recognize that these do not go far enough, and that collective action is needed to inform systemic change. (shrink)

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

This article systematically reviews studies investigating the effect of three operationalizations of complexity in emotion experience on situat...

We say that E is R-sparse if f(Ek) has no interior, for each k 2 N and f : Rk ! R de nable in R. (Throughout, \de nable" means \de nable without parameters".) In this note, we consider the extent to which basic metric and topological properties of subsets of R de nable in (R;E)# are determined by the corresponding properties of subsets of R de nable in (R;E), when R is an o-minimal expansion of (R;<;+;0;1) and E is (...) R-sparse. The precise statement of the main result is a bit complicated, but we can state some special cases now. (shrink)

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human‐nonhuman chimeric research. Led by bioethics researchers working closely with an (...) interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human‐nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics’ previous focus on human‐centered questions about the ethics of “humanization” and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less‐siloed governance and oversight and more‐comprehensive public communication. (shrink)