© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

This article provides ethical guidance on using race in health research as a variable or in defining the study population. To this end, a plain, non-exhaustive checklist is provided for researchers and research ethics committees, preceded by a brief introduction on the need for justification when using race as a variable or in defining a study population, the problem of exoticism, that distinctions pertain between race, ethnicity and ancestry, the problematic naming of races, and that race does not serve well (...) as a presumed biological construct in genetic research. (shrink)

Background: The Declaration of Helsinki, the World Medical Association’s statement of ethical guidelines regarding medical research, is published in the three official languages of the WMA: English, French and Spanish.Methods: A detailed comparison of the three official language versions was carried out to determine ways in which they differed and ways in which the wording of the three versions might illuminate the interpretation of the document.Results: There were many minor linguistic differences between the three versions. However, in paragraphs 1, 6, (...) 29, 30 and in the note of clarification to paragraph 29, there were differences that could be considered potentially significant in their ethical relevance.Interpretation: Given the global status of the Declaration of Helsinki and the fact that it is translated from its official versions into many other languages for application to the ethical conduct of research, the differences identified are of concern. It would be best if such differences could be eliminated but, at the very least, a commentary to explain any differences that are unavoidable on the basis of language or culture should accompany the Declaration of Helsinki. This evidence further strengthens the case for international surveillance of medical research ethics as has been proposed by the WMA. (shrink)

SummaryIntense, sustained nursing lengthens inter-birth intervals and is causally linked with low natural fertility. However, in traditional settings, the effects of such nursing on fertility are difficult to disentangle from those of nutrition. Results from an prospective, direct observational study of reproductive function in well-nourished Amele women who nurse intensively and persistently but who also have high fertility are here presented. Endocrine measures show that ovarian activity resumes by median 11·0 months postpartum. Median duration of postpartum amenorrhoea is 11·3 months, (...) time to next conception is 19·0 months, and the inter-birth interval is 28·0 months. Average life time fertility is 6·8. High fertility in Amele women is due both to refractoriness of reproductive function to suckling stimuli, and to maintenance of equivalent age-specific fertility rates across the reproductive life span. (shrink)

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates. BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our ’learner’ discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the (...) relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system. (shrink)

Sankary et al. (2022) report the results of an empirical study on research participant experiences of exiting research at the end of clinical trials of deep-brain-stimulation (DBS) and responsive n...

A political theorist considers the interface between political and moral theory. Drawing freely from classical theories of human nature and morality, Professor Ryn argues that constitutional, representative democracy coheres better with human social ethical aspirations than does democracy by plebiscite, unqualified majority rule.

Les décisions politiques sur les risques environnementaux complexes font fréquemment intervenir des éléments scientifiques contestés. Il n’y a généralement pas de « faits » qui conduisent à une politique correcte unique. Les éléments de preuve qui sont intégrés dans les avis scientifiques destinés à une décision politique nécessitent une évaluation de leur qualité. En 2003, l’Agence néerlandaise d’évaluation environnementale a adopté une méthode standardisée, désignée sous le nom de « guide », dans le cadre de laquelle les principaux aspects de (...) la production et de l’utilisation des connaissances sont présentés grâce à une liste de contrôle visant à l’évaluation et à la communication des incertitudes. Dans cet article, nous présentons des résultats de l’application de ce guide à la controverse sur les risques des particules en suspension. La délibération active sur l’incertitude dans un contexte d’expertise entraîne un processus d’apprentissage commun entre les experts et les décideurs politiques, ce qui conduit à une meilleure prise de conscience du phénomène d’incertitude et de ses implications politiques.Policy decisions on complex environmental risks often involve disputed science. Typically, there are no “ facts” to support a single unequivocally correct policy. The evidence provided in scientific studies for policy-making decisions requires high-quality assessment. In 2003, the Netherlands Environmental Assessment Agency adopted a standardized method, referred to as “guidelines”, whereby key quality aspects of knowledge production and use are presented in the form of a checklist for uncertainty assessments and communication. In this article, we present the outcomes of applying the guidelines in controversies on the risks of ambient particulate matter. In the policy–advisory context, active deliberation on uncertainty produces a common learning process for advisors and policy makers, which leads to a deeper understanding and increased awareness of the phenomenon of uncertainty and its policy implications. (shrink)

Le culte grandiose de Kali, la Mère, son incomparable symbolisme, ses litanies et ses chants, embrasse l'âme de l'univers qu'il glorifie comme aucune conception religieuse ne le fit jamais. La terrifiante déesse sème la peste et les pires ravages sur ses pas, tout en accordant sa grâce et sa clémence à ses enfants assez hardis pour soulever l'horrible masque derrière lequel elle se cache la figure. Ceux-là retrouveront les traits radieux qui ont enchanté leur enfance. La sublime conception de Kali, (...) la Mère, découle d'une philosophie moniste qui s'écarte pourtant sensiblement de la philosophie Védanta de Shankara. Tous deux partent, il est vrai, de la même idée. Ils admettent l'un et l'autre une substance une, indivisible et éternelle, que les Védantins appellent Brahma et les adorateurs de Kali, la Mère, Siva. Mais il y a divergence quant aux manifestations. Pour Shankara il n'y a qu'illusion. Il tranche le lien qui rattache le phénomène à l'absolu. Il se demande qui a pu susciter l'apparence. Mais, l'absolu étant la vérité même, il n'a pu engendrer l'apparence pas plus que la lumière n'aurait pu engendrer l'obscurité. Qu'y avait-il donc de commun entre les Brahmas et Maya? A première vue il semble qu'il n'y a aucun rapport. Pour Shankara il n'était besoin d'aucune relation, puisque Maya n'existe pas en réalité et que le monde n'est que mirage. Le monde n'existe que pour l'esprit qui est lui-même sujet aux hallucinations. Adorer la Mère, c'est accepter l'univers dans ses aspects les plus terrifiants. Cette philosophie est diamétralement opposée au christianisme dans son culte du Dieu d'amour, du Père plein de miséricorde. Le christianisme enseigne que tout se fait pour notre bien, tandis que pour les adorateurs de Kali, l'univers est féroce et hostile à l'homme, qui avant tout doit se montrer supérieur aux événements. Mais Kali n'est pas seulement la destructrice. Si elle démolit inexorablement toutes les formes vitales qui ont fait leur temps et qui se détériorent, elle en crée au fur et à mesure des nouvelles. C'est dans cette conception de la Mère qu'il faut chercher tout d'abord le mystère de l'esprit indien. Dans son essence la plus intime la mère du monde est l'absolu, est Siva même. Comme telle elle représente la connaissance, l'entité et la joie absolues. Pour les adorateurs de Kali les mots Mantram Saham (je suis elle) renferment la clef de la vie et dissipent crainte et tristesse. (shrink)

Notre époque, traversée de courants mystiques, manifeste un intérêt tout particulier pour les idées du neo-platonicien Plotin. Pour le platonicien l'univers participe à l'idée. Platon considérait les choses comme le reflet de l'idée, ce que Plotin se refusait à admettre. La diversité dont la vie fait preuve atteste son inépuisable richesse, et si les choses dans leur état particulier sont imparfaites et défectueuses, c'est que chaque chose représente sa particularité d'une façon imparfaite. Le dualisme platonicien se retrouve chez Plotin; à (...) côté du monde de l'erreur et de l'apparence il situe celui de la vérité et de la réalité. Mais l'ordre des deux mondes étant différent, nécessairement les catégories qui y règnent diffèrent. Contrairement au monde du temps et de l'espace, où tout est désaccord et combat, l'accord et l'harmonie règnent dans le monde de l'idée. D'après Platon l'idée de l'être implique l'idée du repos. Pour Plotin le mouvement et le repos ne sont pas incompatibles. Il y a encore un point de divergence entre les deux philosophes. Tandis que Platon conçoit le bien comme idée, Plotin le superpose au monde des idées et l'en sépare. A l'oppossé du maître il n'était pas dualiste mais moniste. La conception platonicienne du bien est purement éthique, c.a.d. humaine, la conception de Plotin est plus cosmique. L'univers lui apparaît comme une trinité: le monde sensoriel, le monde idéal et l'unité suprême, et il leur découvre une base commune. Tout en admettant l'imperfection du monde, Plotin nie qu'il soit mauvais et méprisable. Il se tourne contre les Gnostiques chrétiens qui prêchent le mépris du monde, et s'oppose vigoureusement aux doctrines qui font des jouissances sensuelles l'unique but de la vie. L'exercice de la vertu n'est autre chose que le moyen de s'unir à Dieu. Pour Plotin la vertu n'est donc pas une fin en elle-même, mais elle est subordonnée à un but qui la dépasse. (shrink)

This paper, a contribution to “micro set theory”, is the study promised by the first author in [M4], as improved and extended by work of the second. We use the rudimentarily recursive functions and the slightly larger collection of gentle functions to initiate the study of provident sets, which are transitive models of $\mathsf{PROVI}$, a subsystem of $\mathsf{KP}$ whose minimal model is Jensen’s $J_{\omega}$. $\mathsf{PROVI}$ supports familiar definitions, such as rank, transitive closure and ordinal addition—though not ordinal multiplication—and Shoenfield’s unramified (...) forcing. Providence is preserved under directed unions. An arbitrary set has a provident closure, and the extension of a provident $M$ by a set-generic $\mathcal{G}$ is the provident closure of $M\cup\{\mathcal{G}\}$. The improvidence of many models of $\mathsf{Z}$ is shown. The final section uses similar but simpler recursions to show, in the weak system $\mathsf{MW}$, that the truth predicate for $\dot{\varDelta}_{0}$ formulæ is $\Delta_{1}$. (shrink)

Thirty years after the conference that gave rise to The Structure of Scientific Theories, there is renewed interest in the nature of theories and models. However, certain crucial issues from thirty years ago are reprised in current discussions; specifically: whether the diversity of models in the science can be captured by some unitary account; and whether the temporal dimension of scientific practice can be represented by such an account. After reviewing recent developments we suggest that these issues can be accommodated (...) within the partial structures formulation of the semantic or model-theoretic approach. (shrink)

Perforation or gap formation in a vegetation is a major process in landscape transformation. The occurrence of gaps profoundly alters the microclimatical conditions in a vegetation. A method is proposed to quantify perforation by using the three main 2-D characteristics of the gaps: area, number and boundary length. New measures are developed by normalizing the observed values to the reference status of minimum and maximum perforation. As minimum perforation status, the presence of one single gap with area equal to the (...) map resolution is assumed. The new measures are combined using a 3-D Euclidean distance to visualize the process and to detect changes. The method is exemplified using a field case of gaps in a tropical terra firme rainforest at Tiputini, Ecuador. (shrink)

Until recently, psychologists have conceptualised and studied trust in God (TIG) largely in isolation from contemporary work in theology, philosophy, history, and biblical studies that has examined the topic with increasing clarity. In this article, we first review the primary ways that psychologists have conceptualised and measured TIG. Then, we draw on conceptualizations of TIG outside the psychology of religion to provide a conceptual map for how TIG might be related to theorised predictors and outcomes. Finally, we provide a research (...) agenda for future empirical work in this area, as well as practical applications for counsellors and religious leaders. (shrink)

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically adjusts blood glucose (...) to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation. (shrink)