Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cells. Within 90 minutes after receiving a single intravenous dose of the drug, all six volunteers had a systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours after infusion, they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulation. Severe and unexpected depletion of lymphocytes and monocytes occurred within 24 hours after infusion. All six patients were transferred to the care of the authors at an intensive care unit at a public hospital, where they received intensive cardiopulmonary support (including dialysis), high-dose methylprednisolone, and an anti-interleukin-2 receptor antagonist antibody. Prolonged cardiovascular shock and acute respiratory distress syndrome developed in two patients, who required intensive organ support for 8 and 16 days. Despite evidence of the multiple cytokine-release syndrome, all six patients survived. Documentation of the clinical course occurring over the 30 days after infusion offers insight into the systemic inflammatory response syndrome in the absence of contaminating pathogens, endotoxin, or underlying disease.

UK Efficacy and Mechanism Evaluation Programme and National Institutes of Health.

This article offers a new test of the mobilisation thesis of Internet effects on individual political participation using data from an NOP survey of 1,972 UK adults during May 2002. The analysis differs from that of previous studies in that it significantly widens the understanding of the dependent variable-online participation-as well as introducing new Internet-specific variables as explanatory factors for this new type of participation. Using this broader 'contextualised' model of online political activity we find support for the idea that the Internet is expanding the numbers of the politically active, specifically in terms of reaching groups that are typically inactive or less active in conventional or offline forms of politics. In drawing these conclusions our article joins with a growing body of literature calling for the re-evaluation of the so-called normalisation thesis which argues that ultimately the Internet will lead to a further narrowing of the pool of politically active citizens by reinforcing existing levels of engagement. At a broader level we consider the findings point to the need for scholars in the area to work towards a more sophisticated theoretical and empirical modelling of participation in the online environment.This study builds on these critiques to provide a more comprehensive test of the mobilisation effects of the Internet than has hitherto been presented, within the European context. We do this by profiling and critiquing the empirical literature supporting the normalisation theory and then develop a more detailed or contex- BJPIR: 2005 VOL 7, 561-583

Infection of the mucous layer of the human stomach by Helicobacter pylori requires the bacterium to be motile and presumably chemotactic. Previous studies have shown that fully functional flagella are essential for motility and colonization, but the role of chemotaxis remains unclear. The two-component regulatory system CheA/CheY has been shown to play a major role in chemotaxis in other enteric bacteria. Scrutiny of the 26695 genome sequence suggests that H. pylori has two CheY response regulators: one a separate protein (CheY1) and the other (CheY2) fused to the histidine kinase sensor CheA. Defined deletion mutations were introduced into cheY1, cheY2, and cheA in H. pylori strains N6 and SS1. Video tracking revealed that the wild-type H. pylori strain moves in short runs with frequent direction changes, in contrast to movement of cheY2, cheAY2, and cheAY2 cheY1 mutants, whose motion was more linear. The cheY1 mutant demonstrated a different motility phenotype of rapid tumbling. All mutants had impaired swarming and greatly reduced chemotactic responses to hog gastric mucin. Neither cheY1 nor cheAY2 mutants were able to colonize mice, but they generated a significant antibody response, suggesting that despite impaired chemotaxis, these mutants were able to survive in the stomach long enough to induce an immune response before being removed by gastric flow. Additionally, we demonstrated that cheY1 failed to colonize gnotobiotic piglets. This study demonstrates the importance of the roles of cheY1, cheY2, and cheA in motility and virulence of H. pylori.

The growth of party and candidate activity on the World Wide Web over the past 5 years has provoked much comment and criticism. Although initially most assessments were descriptive and anecdotal, more recent studies have taken a more systematic and quantitative approach to this topic. This article builds on the existing literature by developing a coding scheme that addresses two basic questions applicable to all political Web sites: (a) what the purpose of the sites are, and (b) how effectively they deliver their contents. In doing so, this article attempts to standardize the study of party Web sites and to promote the growth of cross-national and longitudinal comparative research in this area.