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Purpose We evaluated national outpatient antimicrobial prescription trends in relation to the first United States case of inhalational anthrax due to the intentional delivery of Bacillus anthracis (B. anthracis) spores. Methods We queried IMS HEALTH's National Prescription Audit Plus7™ database for two 6-month periods (July–December) in 2001 and 2000 to describe outpatient prescription trends of antimicrobials recommended during the Centers for Disease Control and Prevention's (CDC) postexposure prophylaxis campaign. Results Overall, antimicrobial utilization for the referent 6-month time frame was greater in 2000 compared to 2001. In contrast, ciprofloxacin utilization was greater in 2001 during October, the month following the index case, increasing by more than 40% over utilization in October 2000. Similarly, doxycycline utilization increased by 30% during October/November. This corresponded to relative increases in US utilization for ciprofloxacin of approximately 160 000 prescriptions for the month of October and for doxycycline of approximately 96 000 prescriptions during October and 120 000 prescriptions for November. Conclusions We conclude more widespread prescribing of ciprofloxacin and doxycycline occurred in response to the first US bioterrorist-associated anthrax attacks than was warranted based upon confirmed or suspected B. anthracis exposure alone. Published in 2003 by John Wiley & Sons, Ltd.

Etude de la signification de l'image du voile utilisee par J. Rawls pour exposer sa conception des principes de la justice dans son ouvrage intitule «A theory of justice». Se referant a l'histoire culturelle et religieuse de l'artefact du voile, l'A. montre que le voile de l'ignorance est celui qui separe le moi noumenal du moi social

Intrinsic dynamics of DNA plays a crucial role in DNA protein interactions and has been emphasized as a possible key component for in vivo chromatin organization. We have prepared an entangled DNA microtube above the overlap concentration by exploiting the complementary cohesive ends of lambda-phage DNA, which is confirmed by atomic force microscopy and agarose gel electrophoresis. Photon correlation spectroscopy further confirmed that the entangled solutions are found to exhibit the classical hydrodynamics of a single chain segment on length scales smaller than the hydrodynamic length scale of single lambda-phage DNA molecule. We also observed that in 41.6% (gm water/gm DNA) hydrated state, lambda-phage DNA exhibits a dynamic transition temperature (T-dt) at 187 K and a crossover temperature (T-c) at 246 K. Computational insight reveals that the observed structure and dynamics of entangled lambda-phage DNA are distinctively different from the behavior of the corresponding unentangled DNA with open cohesive ends, which is reminiscent with our experimental observation.

A review of the Food and Drug Administration (FDA) Adverse Drug Reaction (ADR) file system. This paper describes the current operations for maintaining the on-line computerized data entry, storage and retrieval programs, and the microfilm retrieval system. Other technology developments discussed include data diskette exchange and laser disc storage and retrieval.

The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.

OBJECTIVE—To describe the use of oral antidiabetic drugs for management of type 2 diabetes in the U.S. from 1990 through 2001. RESEARCH DESIGN AND METHODS—Data on oral antidiabetic drugs were derived from two pharmaceutical marketing databases from IMS Health, the National Prescription Audit Plus and the National Disease and Therapeutic Index. RESULTS—In 1990, 23.4 million outpatient prescriptions of oral antidiabetic agents were dispensed. By 2001, this number had increased 3.9-fold, to 91.8 million prescriptions. Glipizide and glyburide, two sulfonylurea medications, accounted for ∼77% of prescriptions of oral antidiabetic drugs in 1990 and 35.5% of prescriptions in 2001. By 2001, the biguanide metformin (approved in 1995) had captured ∼33% of prescriptions, and the thiazolidinedione insulin sensitizers (rosiglitazone and pioglitazone marketed beginning in 1999) accounted for ∼17% of market share. Compared with patients treated in 1990, those in 2001 were proportionately younger and they more often used oral antidiabetic drugs and insulin in combination. Internists and general and family practitioners were the primary prescribers of this class of drugs. CONCLUSIONS—Consistent with the reported increase in the prevalence of type 2 diabetes, the number of dispensed outpatient prescriptions of oral antidiabetic drugs increased rapidly between 1990 and 2001. This period was marked by an increase in the treatment of younger people and the use of oral antidiabetic drugs in combination. With the approval in the last decade of several new types of oral antidiabetic medications with different mechanisms of action, options for management of type 2 diabetes have expanded.

FAITH IN FREEDOM Beyond the liberal religious disputations of Constant and Tocqueville, a wider matter solicits our attention: how may faith be said to support political authority, participate in liberty, and establish relations with the new post-Revolutionary society? It might at first seem that liberalism had made men and nations free of faith, thus serving as midwife for the secularist dreams of the Enlightenment. But, like the seventeenth, the nineteenth century in France is justly called “religious” – especially in the sense of a rebuilding, a “reveil” in which politics has its part. What is the part of liberal thought in this project? As regards the relationship of practical truth, religious belief, and the liberty and dignity of man, the surface position of liberalism is clear. Liberty of faith or, more generally, of conscience is one of a number of guarantees without which a regime suited to liberty and dignity cannot exist. But is this merely a permission to have a faith or not to have it – an indifference of politics to the question of faith – or does it enjoin some new sort of faith? The moral objective of many liberalisms (though not all) is to define an ideal order toward which human beings will strive through education and by shedding their bondage to the grosser appetites. This “logic of transcendence,” as Benichou puts it, must be “created outside the pathways of Christian [or presumably any other] dogmatism.” But can there be a transcendent logic of liberty operating as an ideal without the guidance of a cohesive cult?

This book is the last completed work of one of the most distinguished political theorists and intellectual historians of our time. Focusing on the political ideas and activities of leading French liberals from approximately 1805 into the Second Empire, Professor Kelly presents a distinctive blend of ideological and intellectual history, biography, analysis of French regimes and their changes, and his own reflections concerning the wide and still highly pertinent range of issues considered. Beginning with a subtle analysis of the complex patterns of agreement and disagreement between the liberalisms of Benjamin Constant and Alexis de Tocqueville, the work offers a sophisticated examination of the attempts of a sequence of liberal thinkers to harmonize their commitments to political and civil liberty with one another, and with a profound desire for a legitimate and stable political order.

SOCIAL SETTINGS OF THE POLITICAL SELF As the conclusion to the last chapter suggests, the relation of the individual and private citizen to the opinions of society and the powers of government is one of the chief modes by which the political theories of Constant and Tocqueville are to be distinguished. An expanded domain of the self combined with a normative supremacy of public opinion had, for the most part, characterized the philosophical project of the eighteenth century. Constant, while greatly sobered by revolution and reaction, is obedient to this idea. For him, these goals are in harmony. Liberal politics is fundamentally a safeguard of the educable inner capacities of the human being and their outward projection as expressive rights. Tocqueville is disabused of that simplicity. He does not deny Constant's priority of “liberty against” (for he, too, has a “garantist” view of political authority), but he fears the unstable context of uniformity that democratic self-disclosure has helped to create, a liberation leading to softer but stronger servitudes. “ In democratic times,” he writes, “what is most unstable, in the midst of the instability of everything, is the heart of man.” This is an instability predicated both as sameness and as separateness. Tocqueville deplores, and probably exaggerates in his aristocrat's heart, the atomization of modern, and especially post-Revolutionary, French society. Insofar as Constant acknowledges that danger, he tends to interpret it as a consequence of “despotic” residues, seeing uniformity “as the immediate and inevitable consequence of the spirit of conquest [of Napoleon].” Terms appropriate to our inquiry such as “self” or “individual” or “individualism” have long had contested resonances.