© 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)

The spectacular development of medical knowledge over the last two centuries has brought intrusive advances in the capabilities of medical technology. These advances have been remarkable over the last century, but especially over the last few decades, culminating in such high technology interventions as heart transplants and renal dialysis. These increases in medical powers have attracted societal interest in acquiring more such knowledge. They have also spawned concerns regarding the use of human subjects in research and regarding the byproducts of (...) basic research as in the recent recombinant DNA debate. As a consequence of the development of new biomedical knowledge, physicians and biomedical scientists have been placed in positions of new power and responsibility. The emergence of this group of powerful and knowledgeable experts has occasioned debates regarding the accountability of physicians and biomedical scientists. But beyond that, the very investment of resources in the acquisition of new knowledge has been questioned. Societies must decide whether finite resources would not be better invested at this juncture, or in general, in the alleviation of the problems of hunger or in raising general health standards through interventions which are less dependent on the intensive use of high technology. To put issues in this fashion touches on philosophical notions concerning the claims of distributive justice and the ownership of biomedical knowledge. (shrink)

We argue in favour of the general proposition that the nature of reasoning is best understood within a context of its origins and development. A major dimension of what develops in the years from childhood to adulthood, we propose, is increasing meta-level monitoring and management of cognition. Two domains are examined in presenting support for these claims—multivariable causal reasoning and argumentive reasoning.

The thesis I shall defend is this. Many philosophical arguments which involve an appeal to ordinary linguistic usage turn out themselves to use key terms in a non-ordinary way, and to have no point unless they do so. They therefore use terms in a way which, if their appeal is justified, is unjustified. I shall first illustrate this thesis with some examples. Then I shall try to show why in general the situation exists.

Constructive engagement in international business practice is defined as purpose-driven behavior in which economic contributions by the foreign investor also advance social progress in the host country. This paper distinguishes between amoral and moral social agency, and proposes a model of principled constructive engagement that describes a principled constructive engagement regime enacted in a disciplined, morally-directed manner.

The idea of God’s action in history was prominent in the Biblical theology of the past generation. This theology was generally opposed to philosophic explication of its doctrine of God, and consequently it is difficult to say just what it meant by divine action. In any case, that movement faded and, with it, talk of God’s acts.

Copyright © 2015 by the Society of Criti. Objective: Global lung stress varies considerably with low tidal volume ventilation for acute respiratory distress syndrome. High stress despite low tidal volumes may worsen lung injury and increase risk of death. No widely available parameter exists to assess global lung stress. We aimed to determine whether the volume delivered during a recruitment maneuver is inversely associated with lung stress and mortality in acute respiratory distress syndrome. Design: Substudy of an acute respiratory distress (...) syndrome clinical trial on esophageal pressure-guided positive end-expiratory pressure titration. Setting: U.S. academic medical center. Patients: Forty-two patients with acute respiratory distress syndrome in whom airflow, airway pressure, and esophageal pressure were recorded during the recruitment maneuver. Interventions: A single recruitment maneuver was performed before initiating protocol-directed ventilator management. Recruitment maneuvers consisted of a 30-second breath hold at 40 cm H2O airway pressure under heavy sedation or paralysis. VRM was calculated by integrating the flow-time waveform during the maneuver. End-inspiratory stress was defined as the transpulmonary pressure during end-inspiratory pause of a tidal breath and tidal stress as the transpulmonary pressure difference between end-inspiratory and end-expiratory pauses. Measurements and Main Results: VRM ranged between 7.4 and 34.7 mL/kg predicted body weight. Lower VRM predicted high end-inspiratory and tidal lung stress. After adjusting for Pao2/Fio2 and either driving pressure, tidal volume, or plateau pressure and positive end-expiratory pressure, VRM remained independently associated with both end-inspiratory and tidal stress. In unadjusted analysis, low VRM predicted increased risk of death. VRM remained significantly associated with mortality after adjusting for study arm. Conclusions: Low VRM independently predicts high lung stress and may predict risk of death in patients with acute respiratory distress syndrome. (shrink)

The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct.