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Pituitary growth hormone (GH)-secreting cells regulate growth and metabolism in animals and humans. To secrete highly ordered GH pulses (up to 1,000-fold rise in hormone levels in vivo), the pituitary GH cell population needs to mount coordinated responses to GH secretagogues, yet GH cells display an apparently heterogeneous scattered distribution in 2D histological studies. To address this paradox, we analyzed in 3D both positioning and signaling of GH cells using reconstructive, two-photon excitation microscopy to image the entire pituitary in GH-EGFP transgenic mice. Our results unveiled a homologous continuum of GH cells connected by adherens junctions that wired the whole gland and exhibited the three primary features of biological networks: robustness of architecture across lifespan, modularity correlated with pituitary GH contents and body growth, and connectivity with spatially stereotyped motifs of cell synchronization coordinating cell activity. These findings change our view of GH cells, from a collection of dispersed cells to a geometrically connected homotypic network of cells whose local morphology and connectivity can vary, to alter the timing of cellular responses to promote more coordinated pulsatile secretion. This large-scale 3D view of cell functioning provides a powerful approach to identify and understand other networks of endocrine cells that are thought to be scattered in situ. Many dispersed endocrine systems exhibit pulsatile outputs. We suggest that cell positioning and associated cell-cell connection mechanisms will be critical parameters that determine how well such systems can deliver a coordinated secretory pulse of hormone to their target tissues. biological rhythms | endocrinology | systems biology | connectivity | calcium

Why did whigs consider the Treaty of Utrecht to be an imperial disaster? Contemporary scholarship makes this a difficult question to answer. Imperial historians insist that it was an imperial triumph. While political historians point to rough-and-tumble party politics that was not about empire. This article aims to recover the rich intellectual history of party political debate about empire in the age of Anne. I suggest that there was bitter conflict between tories who sought territorial empire based on South American mines, and whigs who sought a manufacturing empire based on penetrating South American markets with British manufactures. The Sacheverell trial and its aftermath marked a turning point in British imperial policy. As a result the whigs felt betrayed, venting their anger in the immediate aftermath of the Hanoverian succession. [ABSTRACT FROM AUTHOR]

The article presents the author's response to critiques of his essay "Rethinking Mercantilism: Political Economy, the British Empire, and the Atlantic World in the Seventeenth and Eighteenth Centuries," published in the issue. It examines mercantilism and British economic and political debates, particularly commenting on British Whig views. The author also reflects on Jamaican politics and British policy toward Jamaica in the late seventeenth century, exploring the tenure of the Duke of Albemarle as the governor of Jamaica.

An essay is presented on the mercantile system and British imperialism in the Atlantic world in the seventeenth and eighteenth centuries. The author examines historians' treatments of early modern ideas on political economy, commenting on the thought of several individuals, including philosopher Adam Smith, economic writer Carew Reynell, and writer and explorer Sir Walter Ralegh. The author reflects on the notion of trade as a zero-sum game. The views of British Whigs and Tories are considered.

The article presents the author's response to the reviews of his book "1688: The First Modern Revolution." He has been grateful of the varied reviews of the iconoclastic book by eminent scholars including Tim Blanning, Lisa Forman Cody, and Don Herzog. However, the author argues that the revolutionaries of 1688-89 had radically transformed the political economy, foreign policy, and the established churches in England.

The need to assess subtle, potentially exploitable changes in serial structure is paramount in the analysis of financial and econometric data. We demonstrate the utility of approximate entropy (ApEn), a model-independent measure of sequential irregularity, towards this goal, via several distinct applications, both empirical data and model-based. We also consider cross-ApEn, a related two-variable measure of asynchrony that provides a more robust and ubiquitous measure of bivariate correspondence than does correlation, and the resultant implications to diversification strategies. We provide analytic expressions for and statistical properties of ApEn, and compare ApEn to nonlinear (complexity) measures, correlation and spectral analyses, and other entropy measures. [ABSTRACT FROM AUTHOR]

Complement-dependent cytotoxicity (CDC) is a key mechanism of Rituximab (RTX) action in killing non-Hodgkin’s lymphoma (NHL) cells both in vitro and probably in vivo. A DeImmunized, mouse/human chimeric monoclonal antibody (Mab), H17, specific for cell-associated complement C3 cleavage products, C3b and iC3b, was generated to enhance RTX-mediated killing of target cells by CDC. When NHL cell lines were treated with RTX and H17 in the presence of complement for 1 h, there was 40–70% more cell death than that observed with RTX alone. The enhancing effect of H17 was also seen over longer treatment periods. H17 was tested ex vivo against primary cells from NHL and chronic lymphocytic leukemia (CLL) patients. In RTX-resistant NHL samples, H17 enhanced RTX-mediated killing; in the remaining samples RTX + complement alone promoted more than 80% killing, and no significant enhancement was observed. The H17 antibody also increased RTX-mediated killing in four out of nine CLL samples. H17 may have therapeutic applications in NHL and CLL treatment as an adjunctive therapy to RTX. It might also enhance the activity of other therapeutic antibodies that work through CDC. [ABSTRACT FROM AUTHOR]

Examines a canarypox virus (ALVAC) expressing cytomegalovirus (CMV) glycoprotein for the development of a vaccine against CMV. Drugs received by the patients under study; Ability of ALVAC-CMV to induce potentially protective levels of neutralizing antibodies.

Argues that a public sphere as conceptualized by German social theorist Jurgen Habermas emerged in later 17th-century English political culture, precipitated largely by a thirst for political discussion and a desire to preserve English liberties. Role of coffeehouses in promoting political discourse; Widespread acceptance of the value of public opinion; Popularity of coffee during the period.

Examines the differential orderliness of the growth hormone (GH) release process in castrated rats. Distinction of male- and female-specific modes of episodic GH; GH secretory pattern; Impact of prepubertal gonadal suppression.

Introduces approximate entropy as a quantification of regularity in time-series data. Potential application to a wide variety of relatively short and noisy time-series data; Relationship to other approaches; Marginal probabilities and full reconstruction; Comparison of two autocorrelated maps.

Objective: We developed and implemented clinical practice guideline (CPG) using computerized tomography (CT) as the initial imaging method in the emergency department management of scaphoid fractures. We hypothesized that this CPG would decrease unnecessary immobilization and lead to earlier return to work.Methods: This observational study evaluated implementation of our CPG, which incorporated early wrist CT in patients with “clinical scaphoid fracture”: a mechanism of injury consistent with scaphoid fracture, anatomical snuff box tenderness, and normal initial plain x-rays. Outcome measures were the final diagnosis as determined by orthopaedic review of the clinical and imaging data. Patient outcomes included time to return to work and patient satisfaction as determined by telephone interview at ten days.Results: Eighty patients completed the study protocol in a regional emergency department.In this patient population CT detected 28 fractures in 25 patients, including six scaphoid fractures, five triquetral fractures, four radius fractures, and 13 other related fractures. Fifty-three patients had normal CT. Eight of these patients had significant ongoing pain at follow up and had an MRI, with only two bone bruises identified. The patients with normal CTs avoided prolonged immobilization (mean time in plaster 2.7 days) and had no or minimal time off work (mean 1.6 days). Patient satisfaction was an average 4.2/5.Conclusion: This CPG resulted in rapid and accurate management of patients with suspected occult scaphoid injury, minimized unnecessary immobilization and was acceptable to patients.[WestJEM. 2009;10(4):227-232.]