Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β‐amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three‐dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including (...) β‐amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. (shrink)

Because rate of force development is an emerging outcome measure for the assessment of neuromuscular function in unfatigued conditions, and it represents a valid alternative/complement to the classical evaluation of pure maximal strength, this scoping review aimed to map the available evidence regarding RFD as an indicator of neuromuscular fatigue. Thus, following a general overview of the main studies published on this topic, we arbitrarily compared the amount of neuromuscular fatigue between the “gold standard” measure and peak, early and late (...) RFD. Seventy full-text articles were included in the review. The most-common fatiguing exercises were resistance exercises, endurance exercises/locomotor activities, isokinetic contractions, and simulated/real sport situations. The most widely tested tasks were knee extension and plantar flexion. The reason for evaluating RFD was lacking in 36% of the studies. On average, the amount of fatigue for MVF was comparable to late RFD but lower compared to both peak RFD and early RFD. Even if the rationale for evaluating RFD in the fatigued state was often lacking and the specificity between test task and fatiguing exercise characteristics was not always respected in the included studies, RFD seems to be a valid indicator of neuromuscular fatigue. Based on our arbitrary analyses, peak RFD and early phase RFD appear even to be more sensitive to quantify neuromuscular fatigue than MVF and late phase RFD. (shrink)

È possibile rivalutare l’attenzione di Popper verso i presocratici in un quadro interpretativo più ampio rispetto a quanto sostenuto finora? Il lavoro propone una generale riconsiderazione del tema principalmente attraverso lo studio delle fonti utilizzate nella lettura di Parmenide e degli altri presocratici, con l’intento di evidenziarne i legami con il contesto generale della filosofia popperiana.

High-spin states in the odd-odd N = Z nucleus Co-54 have been investigated by the fusion-evaporation reaction Si-28(S-32,1 alpha 1p1n)Co-54. Gamma-ray information gathered with the Ge detector array Gammasphere was correlated with evaporated particles detected in the charged particle detector system Microball and a 1 pi neutron detector array. A significantly extended excitation scheme of Co-54 is presented, which includes a candidate for the isospin T = 1, 6(+) state of the 1f(7/2)(-2) multiplet. The results are compared to large-scale shell-model (...) calculations in the fp shell. Effective interactions with and without isospin-breaking terms have been used to probe isospin symmetry and isospin mixing. A quest for deformed high-spin rotational cascades proved negative. This feature is discussed by means of cranking calculations. (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)

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)

It has become increasingly difficult for individuals to exercise meaningful control over the personal data they disclose to companies or to understand and track the ways in which that data is exchanged and used. These developments have led to an emerging consensus that existing privacy and data protection laws offer individuals insufficient protections against harms stemming from current data practices. However, an effective and ethically justified way forward remains elusive. To inform policy in this area, we propose the Ethical Data (...) Practices framework. The framework outlines six principles relevant to the collection and use of personal data—minimizing harm, fairly distributing benefits and burdens, respecting autonomy, transparency, accountability, and inclusion—and translates these principles into action-guiding practical imperatives for companies that process personal data. In addition to informing policy, the practical imperatives can be voluntarily adopted by companies to promote ethical data practices. (shrink)

In its comprehensive overview of Alain Locke's pragmatist philosophy this book captures the radical implications of Locke's approach within pragmatism, the critical temper embedded in Locke's works, the central role of power and empowerment of the oppressed and the concept of broad democracy Locke employed.

The congregation is challenged by modern times that require various life adjustments, including priestly pastoral ministry. Therefore, this study examined the pastoral ministry style for the parishioner’s rural community of St. Petrus Paulus Ampah Diocese in Palangka Raya. A descriptive qualitative approach was used with data collected using participatory observations, in-depth interviews and document studies. Furthermore, the data analysis involved reducing, displaying and process verification. The participants included parish priests, catechists and station council administrators. The results showed that the congregations (...) did not participate in church activities because the pastoral ministry style did not fulfil their needs, economic factors and lack of Catholic faith knowledge. Therefore, the church authorities in pastoral ministry should create a holistic and transformative congregation based on their needs. The current pastoral ministry practice is based on ecclesiastical organisation building and worship (liturgy) focused service. The church should simultaneously conduct catechism practices and charitable diaconia such as social, economic and spiritual activities. This was an interdisciplinary study that focused on practical and pastoral theology, catechesis and social sciences on Catholics’ pastoral ministry style for rural communities.Contribution: Importantly, it contributes to the literature on pastoral style reforms focusing on the congregation’s socio-economic life. Therefore, it can improve the congregation’s interests, ecclesiastical activities and independence. (shrink)

Nous en parlons à peine et leur nom nous échappe. La philosophie les a toujours négligées ; même la biologie les considère comme une simple décoration de l'arbre de la vie. Et pourtant, les plantes donnent vie à la Terre : elles fabriquent l'atmosphère qui nous enveloppe, elles sont à l'origine du souffle qui nous anime. Les végétaux incarnent le lien le plus étroit et élémentaire que la vie puisse établir avec le monde. Sous le soleil et les nuages, en (...) se mêlant à l'eau et au vent, leur existence est une interminable contemplation cosmique. Ce livre part de leur point de vue - celui des feuilles, des racines et des fleurs - pour comprendre le monde non plus comme une simple collection d'objets, ou un espace universel contenant toute chose, mais bien comme l'atmosphère générale, le climat, un lieu de véritable mélange métaphysique. (shrink)

Death in the Clinic fills a gap in contemporary medical education by explicitly addressing the concrete clinical realities about death with which practitioners, patients, and their families continue to wrestle. Visit our website for sample chapters!

In 1975, the English evolutionist William Donald Hamilton held in Brazil a series of lectures entitled “Population genetics and social behaviour”. The unpublished notes of these conferences—written by Hamilton and recently discovered at the British Library—offer an opportunity to reflect on some of the author’s ideas about evolution. The year of the conference is particularly significant, as it took place shortly after the applications of the Price equation with which Hamilton was able to build a model that included several levels (...) of selection. In this paper I mainly analyse the inaugural lecture in which Hamilton proposes a simple model to disprove the hypothesis supported by the British zoologist C. Vero Wynne-Edwards regarding mechanisms to prevent “over-exploitation of the food supply” in “the interests of the survival of the group”. The document presented here is of great historical interest. Not only because manuscript offers a model that—since it was intended for teaching purposes—had never before appeared in the published version, but also because of the general index of the lectures that accompanies it. The latter allows us to make some hypothetical considerations on the relationship and differences between kin-selection, group-selection and inclusive fitness that Hamilton wanted to present to the attentive, well-prepared audience of the foreign university that had invited him. (shrink)

Dans le dernier quart du xix e siècle, l’ambition d’une philosophie scientifique inspire la Psychologie vom empirischen Standpunkt de Franz Brentano. Appelée à refonder sur des bases empiriques l’univers de l’être, cette forme nouvelle de psychologie réactualiserait ainsi, en un sens, un certain héritage de la métaphysique ancienne. Et Brentano parviendrait à assembler dans une même vision systématique les sources de la pensée grecque, en particulier aristotélicienne, et moderne. Mais peut-on vraiment considérer Brentano comme un aristotélicien en raison de son (...) projet psychologique? La question est bien connue et comme Franco Volpi, entre autres, le soutient, il semblerait que l’orientation épistémologique de la psychologie brentanienne ne trouve pas dans l’aristotélisme son véritable motif directeur. Une autre lecture est toutefois possible à nos yeux, si nous considérons qu’à aucun moment Brentano ne prétend faire de la psychologie un moyen pour revenir à Aristote. C’est notre hypothèse de recherche qui nous conduit à lire avec la plus grande attention le traité de 1867, Die Psychologie des Aristoteles : le recours à Aristote resterait alors nécessaire pour comprendre le projet d’une nouvelle psychologie qui n’oublie pourtant pas sa vocation métaphysique. (shrink)

NCG 4.0 is the latest update of the Network of Cancer Genes, a web-based repository of systems-level properties of cancer genes. In its current version, the database collects information on 537 known (i.e. experimentally supported) and 1463 candidate (i.e. inferred using statistical methods) cancer genes. Candidate cancer genes derive from the manual revision of 67 original publications describing the mutational screening of 3460 human exomes and genomes in 23 different cancer types. For all 2000 cancer genes, duplicability, evolutionary origin, expression, (...) functional annotation, interaction network with other human proteins and with microRNAs are reported. In addition to providing a substantial update of cancer-related information, NCG 4.0 also introduces two new features. The first is the annotation of possible false-positive cancer drivers, defined as candidate cancer genes inferred from large-scale screenings whose association with cancer is likely to be spurious. The second is the description of the systems-level properties of 64 human microRNAs that are causally involved in cancer progression (oncomiRs). Owing to the manual revision of all information, NCG 4.0 constitutes a complete and reliable resource on human coding and non-coding genes whose deregulation drives cancer onset and/or progression. NCG 4.0 can also be downloaded as a free application for Android smart phones. (shrink)

"La Nouvelle Alliance (1979), by physicist Ilya Prigogine and philosopher Isabelle Stengers, is both a book on the history and philosophy of thermodynamics and a philosophical essay on man's place in nature. It has given rise to lively interdisciplinary controversy.".

Dans l’Allemagne du xix e siècle, l’édition intégrale du Corpus aristotelicum de l’Académie des sciences de Berlin constitue la condition ayant rendu historiquement possible le « retours à Aristote », dont l’une des figures majeures est sans doute A. F. Trendelenburg. Suivant comme fil conducteur les rapports grammaticaux inhérents aux différentes parties de la proposition, Trendelenburg, le premier, s’engage à démontrer l’ordre sous-jacent au nombre des catégories, laissé pourtant indéterminé par Aristote. Le but est, pour l’essentiel, de découvrir le point (...) de contact originaire entre la pensée, le langage et l’être, en opposition frontale aux résultats de l’idéalisme allemand. C’est donc le lien entre logique et métaphysique qui est au centre de l’exégèse philosophique que Trendelenburg livre aux pages de l’ Aristoteles Kategorienlehre en 1846, sur laquelle nous portons notre attention afin de rétablir les lignes directrices d’un projet dont l’originalité a souvent été confinée aux hypothèses prétendument improductives d’une grammaire spéculative ou délaissée en faveur d’autres épigones du lignage aristotélicien – de Brentano à Heidegger. (shrink)

Pourquoi recourir à la pensée de Dietrich Bonhoeffer pour formuler une contribution philosophique au problème de la tolérance? Et, de surcroît, en dialogue avec la phénoménologie? Homme de pensée et d’action, Bonhoeffer n’est, à proprement parler, ni un phénoménologue ni un penseur de la tolérance. Il est, toutefois, légitime d’envisager sa lutte contre le totalitarisme, tant sur le plan théologique que politique, comme un cas limite susceptible de relever du questionnement sur la nature et la portée de la tolérance elle-même. (...) Et cela en raison du paradoxe auquel Bonhoeffer s’expose dans la tentative de putsch visant l’élimination du Führer à laquelle il participe : la violation non seulement de la loi, mais d’un commandement divin – « tu ne tueras pas » – que Bonhoeffer justifie au nom de sa foi en Dieu. Notre hypothèse de lecture nous conduit dès lors à consacrer une attention particulière à sa thèse d’habilitation, Akt und Sein, où Bonhoeffer formule une critique originale de la phénoménologie notamment heideggérienne, inspirée par la theologia crucis de tradition luthérienne : renonçant à toute tentative d’autodétermination, l’homme, pour Bonhoeffer, ne peut se comprendre que par une ouverture radicale à la transcendance qui coïncide, en dernière instance, avec la dimension authentiquement personnelle de l’homme lui-même ainsi que de la relation entre l’homme et Dieu. (shrink)

This volume is the first in the series to present a long Greek text. The version in the scroll represents an early revision of the Septuagint towards a closer correspondence with the Hebrew text of the Bible - the revision given the name kaige by D. Barthélemy. After an extensive introduction the volume contains an edition of the text, both with and without reconstructions, notes on the palaeography and reconstructions, an extensive commentary on the translation technique, orthographic peculiarities and textual (...) relations, and is supplemented by an index of all words, as well as twenty plates. (shrink)

Dès ses origines, l’écologie a toujours voulu présupposer l’existence parmi les êtres vivants non-humains d’un ordre, d’un équilibre naturel qu’il est nécessaire d’affirmer pour nier ou refouler l’apparente « guerre de tous contre tous » censée régner entre les différentes espèces naturelles. L’article essaie de définir les présupposés théologiques de cette idée d’ordre, et de montrer qu’au centre de l’interaction entre toutes les espèces, il y a une activité d’inclusion et d’inséparation qui se manifeste par l’alimentation.

L’article présente d’abord les débats concernant les commentaires sur la Physique attribués à Siger de Brabant et considère ensuite la possibilité de lui attribuer celui que nous éditons ici. L’examen de critique interne essaie de dégager les doctrines fondamentales et de les comparer avec plusieurs textes de la même période. Les fortes ressemblances littéraires et doctrinales entre cet inédit et les œuvres de Siger de Brabant constituent la preuve que ce commentaire a bien été composé par ce dernier. Ce commentaire (...) apporte des éléments très importants contre l’hypothèse d’un changement doctrinal de Siger de Brabant. (shrink)

Dans la première partie de L'unique fondement possible d'une démonstration de l'existence de Dieu (1763), Kant propose un argument de type ontologique qu'il avait déjà formulé dans ses écrits de 1755. La présente contribution voudrait examiner continuité et changements dans les différentes formulations. Contrairement à ce que soutiennent d'autres chercheurs, j'entends montrer que l'argument de Kant se présente, dès le départ, comme une alternative à celui des auteurs de la tradition wolffienne. Cette innovation comporte certaines difficultés théoriques qui apparaissent clairement (...) dans le texte de 1763. Tout en confirmant la conviction que l'argument ontologique de la tradition wolffienne n'est pas démonstratif, Kant estime ne pas disposer d’un argument alternatif complet, mais seulement de son fondement. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Blossoming of Bioethics at NIHEzekiel J. Emanuel (bio)The establishment of the Department of Clinical Bioethics at the Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH) has coincided with a burgeoning of interest and activity related to bioethical issues at NIH. The department has precipitated a reexamination and revitalization of existing bioethics activities in the Clinical Center and has launched new programs especially in (...) the areas of education and research. In addition, the department contributes to the work of others throughout NIH who address bioethical issues.The Organizational Location of the Department of Clinical BioethicsBefore describing the history and current activities of the Department of Clinical Bioethics, I will say something about it administrative location. Comprehension of the department’s organizational location is essential to understanding its history, role, and function. Prior to interviewing for the position of chair of the department, I did not—and, if truth be told, still do not fully—understand the details of the organizational structure of NIH. I therefore assume that many other bioethicists outside of the Institutes, especially those who do not regularly receive NIH funding, may not fully grasp its organizational intricacies.The Department of Clinical Bioethics is a department within the Warren G. Magnuson Clinical Center, which is NIH’s “hospital.” Hospital is in quotes because all of the patients at the Clinical Center must be enrolled in a research protocol and, therefore, are research subjects. The Clinical Center is where NIH’s clinical researchers admit their research subjects or see them in the out-patient setting. The Department of Clinical Bioethics reports directly to the Director of the Clinical Center, John I. Gallin, M.D., and receives its finances, space, and other resources from the Clinical Center.In this way, the department is part of NIH’s intramural (“inside”) program. People employed by NIH conduct intramural research, training, and other initiatives. The extramural program, which receives approximately 87 percent of NIH’s budget, funds research at institutions outside NIH. The extramural program awards grants and contracts for research, training, and conferences conducted [End Page 455] by investigators who are not affiliated with NIH. The National Human Genome Research Institute’s ELSI (Ethical, Legal, and Social Implications) program, for example, is part of NIH’s extramural program. As part of the NIH intramural program, the Department of Clinical Bioethics is not empowered to fund independent initiatives of people outside of NIH through grants and contracts. However, the department can collaborate with bioethicists and others on research, educational, and other programs outside of NIH and has some funds to support these collaborations.In addition, it is important for bioethicists to understand that NIH is a collection of 24 institutes and centers. Although there is coordination and collaboration between the institutes and centers, each is funded separately, and each has its own scope, programs, administrative structures, research agendas, training priorities, boards of advisors, and so forth. In this sense, NIH is more like a university that has many distinct schools, each with its own dean, faculty, budget, and fund raising office, than one that is tightly integrated and centrally-administered. Within NIH’s diffuse administrative structure, the Department of Clinical Bioethics is located within one of the centers (the Clinical Center) and has defined authority and responsibility only for bioethics within that center; in addition, because the Clinical Center’s mission is to support clinical research at other institutes, the department’ mission includes supporting the work of those institutes as well. Intellectual exchanges and relationships with other institutes and centers are neither pre-ordained nor administratively established; such relationships must be developed case-by-case, topic-by-topic, and initiative-by-initiative.The History and the Development of the Department of Clinical BioethicsThe Department of Clinical Bioethics was launched in late 1996. Although the department’s creation marked a major commitment to bioethics by the Clinical Center, and especially by its director, Dr. Gallin, it was formed on a pre-existing foundation of bioethics activities at NIH. 1In 1977, John Fletcher, Ph.D., was appointed by then Director Mortimer Lipsett as the bioethicist at the Clinical Center; his official title was Assistant for Bioethics... (shrink)

L'article adopte un point de vue plus systématique qu'historique sur la métaphysique de Christian Wolff et, en particulier, sur sa théorie de la conscience. Il s'intéresse à des écrits de controverse de l'époque, impliquant Lange, Ludovici et un certain Bequignole, officier dans l'armée prussienne. Ce dernier, bien qu'il ne fût pas un philosophe professionnel, a relevé dans la Métaphysique allemande quelques défauts graves de la théorie wolffienne de la conscience. En refusant d'attribuer la raison aux bêtes et en décrivant la (...) mémoire du chien en termes très proches de la mémoire de soi propre aux personnes, le philosophe de Halle n'a pas pu éviter de se contredire. The paper adopts a more systematic than historical point of view on Christian Wolff's metaphysics and, in particular, on his theory of consciousness. It is interested in controversial writings of those days with reference e.g. to Lange, Ludovici and an officer of the Prussian army so-called Bequignole ; the latter, though he tvas no professional philosopher, found a few serious defects of Wolff's theory of consciousness in the latter's German Metaphysics. By refusing to grant reason to animals and by describing the dog's memory in terms very close to the self memory specific to persons, Wolff couldn't avoid contradicting himself. (shrink)

L’auteur de cet article propose une relecture inédite d’une vieille question machiavélienne, le rapport entre le modèle antique romain et les temps modernes corrompus, qu’il revisite à la lumière d’un troisième terme : le jugement de Machiavel sur la religion chrétienne. Emanuele Cutinelli Rendina développe ici l’hypothèse d’une césure dans la pensée de Machiavel, représentée par le début du deuxième livre des Discours sur la première Décade de Tite-Live. À partir des premiers chapitre du livre II, le modèle romain ne (...) semble plus être actualisable : inconciliable avec un présent trop corrompu, l’idéal va devenir un mythe. (shrink)

The aim of this cross-sectional study is to investigate the role of psychological inflexibility in the relationship between anxiety and depression and emotional eating in a sample of 123 inpatient Italian adult individuals with obesity. Participants completed the Anxiety and Depression subscales of the Psychological General Well-Being Inventory, the Acceptance and Action Questionnaire, and the Emotional Eating subscale of the Dutch Eating Behavior Questionnaire to assess anxiety and depression, psychological inflexibility, and emotional eating, respectively. Results showed that the indirect effect (...) of PGWBI-A on DEBQ-EE through AAQ-II was significant [b = −0.0155; SE = 0.076; 95% BC-CI ]. Similarly, the indirect effect of PGWBI-D on DEBQ-EE through AAQ-II was significant [b = −0.0383; SE = 0.0207; 95% BC-CI ]. These findings may help to plan and develop specific psychological interventions aimed at addressing emotional eating through targeting psychological inflexibility to be included in obesity treatment programs. (shrink)

We are currently witnessing the emergence of new forms of collective identities and a redefinition of the old ones through networked digital interactions, and these can be explicitly measured and analyzed. We distinguish between three major trends on the development of the concept of identity in the social realm: (1) an essentialist sense (based on conditions and properties shared by members of a group), (2) a representational or ideational sense (based on the application of categories by oneself or others), and (...) (3) a relational and interactional sense (based on interaction processes between actors and their environments). The interactional approach aligns with current empirical and methodological progress in social network analysis. Moreover, it has been argued that, within the network society, the notion of collective identity (Melucci, 1995) in the political field must be rethought as technologically mediated and interactive. We suggest that collective identities should be understood as recurrent, cohesive, and coordinated communicative interaction networks. We here propose that such identities can be depicted by: (a) mapping and filtering a relevant interaction network, (b) delimiting a set of communities, (c) determining the strongly connected component(s) of such communities (the core identity) in a directed graph, and (d) defining the identity audiences and sources within the community. This technical graph–theoretical characterization is explained and justified in... (shrink)

Les designers et théoriciens Ezio Manzini et Virginia Tassinari répondent à la question posée par le titre du dossier, Design is the answer, but what was the question? Si, d’une part, se pose la question de l’impact social et politique du design et de sa responsabilité dans les changements sociaux, de l’autre s’impose une réflexion sur les modes d’action du design et sur les fondements de cette action. Dans cette perspective, Manzini met en avant les pratiques d’ engendrement et d’ (...) engagement comme stratégies d’action communes et communautaires, alors que Tassinari explique comment la définition du designing (plus que du design) comme une action politique nécessite une remise en question du cadre épistémologique qui la fonde. (shrink)