Retroactive causation and the temporal construction of news: contingency and necessity, content and form

This article affords particular attention to the relationship between memory, the narrativization of news and its linear construction, conceived as journalism’s ‘memory- work’. In elaborating upon this ‘work’, it is proposed that the Hegelian notion of retroactive causation (as used by Slavoj Žižek) can examine how analyses of news journalists ‘retroactively’ employ the past in the temporal construction of news. In fact, such retroactive (re)ordering directs attention to the ways in which journalists contingently select ‘a past’ to confer meaning on the present. With regard to current literature, it is noted that a retroactive analysis can highlight two important dialectics within the practice of news journalism: 1) the relation between contingency and necessity; and, 2) the relation between content and form. Indeed, it is argued that this theoretical account offers a novel approach to examining the significance of memory in news journalism as well as the inconsistencies which underscore journalism’s memory-work. It is in accordance with such inconsistency that broader reflections on time, temporality and our relations to the past can be made

Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye.

PURPOSE: The purpose of this study was to characterize local distribution and systemic absorption of the tumor necrosis factor (TNF)-alpha inhibitory single-chain antibody fragment (scFv) ESBA105 following topical administration to the eye in vivo. METHODS: Rabbits received ESBA105 as topical eye drops in two dosing regimens. First, pharmacokinetics after the topical route of administration was compared to the intravenous (i.v.) route by means of applying the identical cumulative daily dose of ESBA105. In a second study rabbits received five eye drops daily for six consecutive days in a lower frequency topical dosing regimen. Kinetics and biodistribution of ESBA105 in ocular tissues and fluids as well as in sera were determined in all animals. RESULTS: After topical administration to the eye, ESBA105 quickly reaches therapeutic concentrations in all ocular compartments. Systemic exposure after topical administration is 25,000-fold lower than exposure after i.v. injection of the identical cumulative daily dose. ESBA105 levels in vitreous humor and neuroretina are significantly higher on topical administration than after i.v. injection. Absolute and relative intraocular biodistribution of ESBA105 is different with topical and systemic delivery routes. Compared to its terminal half-life in circulation (7 hours), the vitreal half-life of ESBA105 is significantly enhanced (16-24 hours). CONCLUSIONS: On topical administration, ESBA105 is efficiently absorbed and distributed to all compartments of the eye, whereby systemic drug exposure is very low. Based on its unique intraocular biodistribution and pharmacokinetics and the absolute intraocular levels reached, topical ESBA105 appears highly attractive for treatment of various ophthalmological disorders

Bayesian model selection in high-dimensional settings

Standard assumptions incorporated into Bayesian model selection procedures result in procedures that are not competitive with commonly used penalized likelihood methods. We propose modifications of these methods by imposing nonlocal prior densities on model parameters. We show that the resulting model selection procedures are consistent in linear model settings when the number of possible covariates p is bounded by the number of observations n, a property that has not been extended to other model selection procedures. In addition to consistently identifying the true model, the proposed procedures provide accurate estimates of the posterior probability that each identified model is correct. Through simulation studies, we demonstrate that these model selection procedures perform as well or better than commonly used penalized likelihood methods in a range of simulation settings. Proofs of the primary theorems are provided in the Supplementary Material that is available online