Modelling within-host spatiotemporal dynamics of invasive bacterial disease

Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single bacterial population. They are also currently poorly understood. Here, we report on the application of sophisticated experimental approaches to map spatiotemporal population dynamics of bacteria during an infection. We analyzed heterogeneous traits of simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic tagged strains [WITS]) in wild-type and gene-targeted mice. WITS are phenotypically identical but can be distinguished and enumerated by quantitative PCR, making it possible, using probabilistic models, to estimate bacterial death rate based on the disappearance of strains through time. This multidisciplinary approach allowed us to establish the timing, relative occurrence, and immune control of key infection parameters in a true host-pathogen combination. Our analyses support a model in which shortly after infection, concomitant death and rapid bacterial replication lead to the establishment of independent bacterial subpopulations in different organs, a process controlled by host antimicrobial mechanisms. Later, decreased microbial mortality leads to an exponential increase in the number of bacteria that spread locally, with subsequent mixing of bacteria between organs via bacteraemia and further stochastic selection. This approach provides us with an unprecedented outlook on the pathogenesis of S. enterica infections, illustrating the complex spatial and stochastic effects that drive an infectious disease. The application of the novel method that we present in appropriate and diverse host-pathogen combinations, together with modelling of the data that result, will facilitate a comprehensive view of the spatial and stochastic nature of within-host dynamics. © 2008 Grant et al.

An experimental study on the load carrying capacity of cold-formed steel studs and panels

A full-scale experimental study on the structural performance of load-bearing wall panels made of cold-formed steel frames and boards is presented. Six different types of C-channel stud, a total of 20 panels with one middle stud and 10 panels with two middle studs were tested under vertical compression until failure. For panels, the main variables considered are screw spacing (300 mm, 400 mm, or 600 mm) in the middle stud, board type (oriented strand board - OSB, cement particle board - CPB, or calcium silicate board - CSB), board number (no sheathing, one-side sheathing, or two-side sheathing), and loading type (1, 3, or 4-point loading). The measured load capacity of studs and panels agrees well with analytical prediction. Due to the restraint by rivet connections between stud and track, the effective length factor for the middle stud and the side stud in a frame (unsheathed panel) is reduced to 0.90 and 0.84, respectively. The load carrying capacity of a stud increases significantly whenever one- or two-side sheathing is used, although the latter is significantly more effective. It is also dependent upon the type of board used. Whereas panels with either OSB or CPB boards have nearly identical load carrying capacity, panels with CSB boards are considerably weaker. Screw spacing affects the load carrying capacity of a stud. When the screw spacing on the middle stud in panels with one-side sheathing is reduced from 600 mm to 300 mm, its load carrying capacity increases by 14.5 %, 20.6% and 94.2% for OSB, CPB and CSB, respectively.