Law Libraries and Laboratories: The Legacies of Langdell and His Metaphor

Law Librarians and others have often referred to Harvard Law School Dean C.C. Langdell’s statements that the law library is the lawyer’s laboratory. Professor Danner examines the context of what Langdell through his other writings, the educational environment at Harvard in the late nineteenth century, and the changing perceptions of university libraries generally. He then considers how the “laboratory metaphor” has been applied by librarians and legal scholars during the twentieth century and into the twenty-first. The article closes with thoughts on Langdell’s legacy for law librarians and the usefulness of the laboratory metaphor

The prevention of contrast induced nephropathy by sarpogrelate in patients with chronic kidney disease: a study protocol for a prospective randomized controlled clinical trial

<p>Abstract</p> <p>Background</p> <p>Contrast-induced nephropathy (CIN) is a serious clinical problem associated with increased morbidity and mortality, particularly in patients with chronic renal insufficiency. Although some agents including hydration with saline are being prescribed to prevent renal deterioration in these high risk patients, their efficacy is not clearly defined and debatable. Therefore additional prophylactic pretreatments are needed.</p> <p>Methods/Design</p> <p>The present study aims to investigate differences in occurrence of CIN after sarpogrelate premedication in patients with chronic kidney disease (CKD). 268 participants, aged 20-85 years with a clinical diagnosis of CKD will be recruited. They will be randomly allocated to one of two conditions: (i) routine treatment without sarpogrelate, and (ii) routine treatment with sarpogrelate (a fixed-flexible dose of 300 mg/day). The primary outcome is the occurrence of CIN during 4 weeks after receiving contrast agent.</p> <p>Discussion</p> <p>As of May 2010, there were no registered trials evaluating the therapeutic potentials of sarpogrelate in preventing for CIN. If sarpogrelate decreases the worsening of renal function and occurrence of CIN, it will provide a safe, easy and inexpensive treatment option.</p> <p>Trial registration</p> <p>NCT01165567</p

IgE Immune Complexes Stimulate an Increase in Lung Mast Cell Progenitors in a Mouse Model of Allergic Airway Inflammation

Mast cell numbers and allergen specific IgE are increased in the lungs of patients with allergic asthma and this can be reproduced in mouse models. The increased number of mast cells is likely due to recruitment of mast cell progenitors that mature in situ. We hypothesized that formation of IgE immune complexes in the lungs of sensitized mice increase the migration of mast cell progenitors to this organ. To study this, a model of allergic airway inflammation where mice were immunized with ovalbumin (OVA) in alum twice followed by three daily intranasal challenges of either OVA coupled to trinitrophenyl (TNP) alone or as immune complexes with IgE-anti-TNP, was used. Mast cell progenitors were quantified by a limiting dilution assay. IgE immune complex challenge of sensitized mice elicited three times more mast cell progenitors per lung than challenge with the same dose of antigen alone. This dose of antigen challenge alone did not increase the levels of mast cell progenitors compared to unchallenged mice. IgE immune complex challenge of sensitized mice also enhanced the frequency of mast cell progenitors per 106 mononuclear cells by 2.1-fold. The enhancement of lung mast cell progenitors by IgE immune complex challenge was lost in FcRγ deficient mice but not in CD23 deficient mice. Our data show that IgE immune complex challenge enhances the number of mast cell progenitors in the lung through activation of an Fc receptor associated with the FcRγ chain. This most likely takes place via activation of FcεRI, although activation via FcγRIV or a combination of the two receptors cannot be excluded. IgE immune complex-mediated enhancement of lung MCp numbers is a new reason to target IgE in therapies against allergic asthma

Renal ischemia–reperfusion injury causes intercalated cell-specific disruption of occludin in the collecting duct

Renal ischemic events open tight junctions and disrupt epithelial polarity. The purpose of this study was to examine the effects of ischemia–reperfusion (IR) injury on expression and distribution of the tight junction proteins, occludin and ZO-1, in the rat kidney. IR injury was induced by clamping both renal pedicles for 30 min and animals were killed at 6 h after the reperfusion. IR injury decreased blood bicarbonate level, but did not persistently alter pH, Na+, K+, or Cl−. In control kidneys, occludin immunoreactivity was intense in the tight junctions in the thick ascending limb, distal convoluted tubule, and collecting duct, moderate in the thin limbs of the loop of Henle, and was not detected in the proximal tubule, glomerulus, and blood vessels. ZO-1 was expressed in the same sites in which occludin was expressed, and additionally was also expressed in the proximal tubule, glomerulus, and vascular endothelial cells. IR kidneys exhibited damaged renal tubular epithelial cells in both proximal tubule and collecting duct segments in the outer medulla. In the collecting duct, the response of intercalated cells and principal cells differed. Following IR injury, intercalated cells, but not principal cells, lost their normal epithelial polarity and were frequently extruded into the tubule lumen. Occludin, instead of being localized to tight junctions, was localized diffusely in the cytoplasm in intercalated cells of IR kidneys. Principal cells, in contrast, were not detectably affected and neither occludin nor ZO-1 expression were altered in response to IR injury. The normal localization of ZO-1 expression to tight junction sites in both the proximal tubule and collecting duct was altered in response to IR, and, instead, ZO-1 expression was present diffusely in the cytoplasm. IR injury did not alter detectably either occludin or ZO-1 localization to the tight junction of the thick ascending limb cells. The abundance of total occludin protein by immunoblot analysis was not changed with IR injury. These results demonstrate that renal IR injury causes tight junction disruptions in both the proximal tubule and the collecting duct, and that altered distribution of the tight junction protein, occludin, may play a critical role in the collecting duct dysfunction which IR induces

Harnessing the Creative Potential of Consumers: Money, Participation and Creativity in Idea Crowdsourcing

Given the growing importance of innovation and consumer engagement, many firms are strongly interested in finding ways to encourage their consumers to generate creative new product ideas for them in their crowdsourcing initiatives. To that end, managers often use monetary rewards – one of the most commonly used managerial tools to stimulate desired behaviors. A critical question in this respect is whether the use of monetary rewards is effective in stimulating creativity and, if so, how large those rewards should be. This study aims to answer these questions. The results of an experiment suggest that introducing monetary rewards does not contribute to the number of new product ideas generated by a single consumer or the novelty of his/her ideas, and when the reward is relatively small it can even be harmful. Monetary rewards, however, are effective in encouraging widespread participation in crowdsourcing initiatives and improving the appropriateness of the new product ideas. As a whole, these findings take us a step further toward better understanding the motivational mechanisms of consumer creativity in new product ideation

CARD15/NOD2 Is Required for Peyer's Patches Homeostasis in Mice

BACKGROUND: CARD15/NOD2 mutations are associated with susceptibility to Crohn's Disease (CD) and Graft Versus Host Disease (GVHD). CD and GVHD are suspected to be related with the dysfunction of Peyer's patches (PP) and isolated lymphoid follicles (LFs). Using a new mouse model invalidated for Card15/Nod2 (KO), we thus analysed the impact of the gene in these lymphoid formations together with the development of experimental colitis. METHODOLOGY/PRINCIPAL FINDINGS: At weeks 4, 12 and 52, the numbers of PPs and LFs were higher in KO mice while no difference was observed at birth. At weeks 4 and 12, the size and cellular composition of PPs were analysed by flow cytometry and immunohistochemistry. PPs of KO mice were larger with an increased proportion of M cells and CD4(+) T-cells. KO mice were also characterised by higher concentrations of TNFalpha, IFNgamma, IL12 and IL4 measured by ELISA. In contrast, little differences were found in the PP-free ileum and the spleen of KO mice. By using chamber experiments, we found that this PP phenotype is associated with an increased of both paracellular permeability and yeast/bacterial translocation. Finally, KO mice were more susceptible to the colitis induced by TNBS. CONCLUSIONS: Card15/Nod2 deficiency induces an abnormal development and function of the PPs characterised by an exaggerated immune response and an increased permeability. These observations provide a comprehensive link between the molecular defect and the Human CARD15/NOD2 associated disorders: CD and GVHD