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)

Il sistema morale e l'agire umano secondo San Tommaso -- Il concetto di legge nella dottrina tomista -- La grazia e le virtù -- La conoscenza della giustizia -- Il pensiero politico di san Tommaso.

Our hospital routine requires that all new admissions must be asked about their code status. It is not uncommon for an otherwise healthy patient to request that a do-not-resuscitate order be placed in their chart. Presumably, these patients who wish to have a DNR order are acting on the belief that should an unforeseen, irreversible condition occur that leads to a cardiac arrest, they would not want to undergo resuscitation. Tragically, we have witnessed several instances in which potentially life-saving interventions (...) were withheld in viable patients in non-arrest settings for reversible conditions because the patients had a DNR order in the chart. Unfortunately, this happens when the treating physicians are not aware of the limited scope of a DNR order and instead use the order as a blanket prohibition against all components of resuscitation. This communication failure is due to misconceptions that patients and their physicians have with regard to such orders. The medical community is well overdue to improve the end-of-life decisions offered to patients beyond relying on the outdated term DNR.LIMITATIONS OF DNR ORDERSDespite the major advances in critical care medicine in the past few decades, doctors have not substantially improved their ability to address end-of-life decisions any better than by using the all-encompassing term DNR. Currently, the term is generally accepted as an order to prohibit the use of interventions to reverse a cardiac or pulmonary arrest.1 2 What is frequently forgotten with the DNR order is that …. (shrink)

Arguing from a sort of reasonable Protestant ethic, Henry offers a worthwhile and sometimes quite practical analysis of a Christian social ideal. In Henry's approach, no "prattling about love" can take the place of justice when the latter is what is needed.—D. J. B.

This work provides an interesting, though sometimes rather sweeping, demonstration that the metaphysical problem of the same and the other is also the central problem of literature and literary criticism. The author defends the analogical imagination as the symbolic counterpart of participation in Platonic metaphysics.--D. C. B.

Using the principles and sometimes the conclusions of his teacher Adolf Stöhr, Cleve insists that he is giving a philosophical interpretation and not simply a philological reconstruction of these Pre-Socratics. The philosophers have been divided into 1) "Religious Reformers", 2) "Philosophers of Nature", 3) "Champions of Culture Politics"—"The Glossomorphics". There will certainly be disagreement on some of Cleve's interpretations but it must be said that Cleve carries through his philosophical reconstruction with admirable lucidity and consistency though, occasionally, some of his (...) criticisms of the "philologists" are rather waspish. Nevertheless, this is a splendid and important study which is a tribute to the author's erudition and insight.—D. J. B. (shrink)

Marsh borrows Richard McKeon's methodological notion of the "problematic" approach to intellectual history. Concentrating on their dialectical character, English criticism from 1650-1800 is explored in the writings of the third Earl of Shaftesbury, Mark Akenside, David Hartley, and James Harris.—D. J. B.

In addition to facing the known competitors in the formal economy, entrepreneurs must also be concerned with rivalry emanating from the informal economy. The informal economy is characterized by actions outside the normal scope of commerce, such as unsanctioned payments and gift-giving, as means of influencing competition. Scholars and policy makers alike have an interest in mitigating the impacts of such informal activity in that it might present an obstacle for legitimate commerce. Received theory suggests that country institutions can enable (...) and constrain productive activity, and, in doing so, influence competitive obstacles in a country. Leveraging 13,670 responses from entrepreneurs distributed across 59 countries, we provide evidence that two particular types of enabling institutions, countries’ property rights regulations and cooperative actions, are useful for lowering the obstacles presented by informal activity. We also find evidence that two constraining institutions, economic and financial regulations lead to more obstacles presented by informal activity. We describe implications for entrepreneurs, policy makers, and future researchers stemming from these findings. (shrink)

Merleau-Ponty had projected a work of considerable dimensions, according to Lefort, which was to have borne the title now given to this posthumous volume. Though the chapters he had actually written out and the notes de travail selected by Lefort for this edition seem to be only introductory parts and suggestions of the larger work, they are already considerable in richness, depth and difficulty. Here we find Merleau-Ponty returning to the problems of his earlier works, showing why the problems posed (...) in the Phenomenology of Perception were "insoluble"; examining in ever greater depth the thought of Descartes, Leibniz, Kant, Hegel, Husserl, Heidegger and Sartre; uncovering the naiveté of scientific thinking and the false sophistication of reflective, dialectical and intuitionistic philosophies. He has moved well beyond phenomenology in the strict sense, toward his own interrogation ontologique and a theory of logic. Lefort has done an extraordinary and exemplary job of organizing, editing and annotating the manuscripts. —A. B. D. and C. D. (shrink)

Summary A study of the metallurgy and manufacturing techniques of a group of eight astrolabes (seven from Lahore, one attributed to India) using non-destructive methods has produced the earliest evidence for systematic use of high-zinc (α?+??) brass. To produce this alloy, the brass industry supplying the Lahore instrument makers must have co-melted metallic copper and zinc. This brass-making technology was previously believed to have been developed on an industrial scale in the nineteenth century in Europe. This work hypothesizes that this (...) technology was used in Lahore on an industrial scale as early as ad 1601. In addition, this work hypothesizes that the α?+?? brass alloy was used specifically for its ease in manufacturing the thin sheet brass required for astrolabe-component manufacture. (shrink)

Summary A study of the metallurgy and manufacturing techniques of a group of eight astrolabes using non-destructive methods has produced the earliest evidence for systematic use of high-zinc brass. To produce this alloy, the brass industry supplying the Lahore instrument makers must have co-melted metallic copper and zinc. This brass-making technology was previously believed to have been developed on an industrial scale in the nineteenth century in Europe. This work hypothesizes that this technology was used in Lahore on an industrial (...) scale as early as ad 1601. In addition, this work hypothesizes that the α + β brass alloy was used specifically for its ease in manufacturing the thin sheet brass required for astrolabe-component manufacture. (shrink)