Coverage and yield of tuberculosis contact investigations in the Netherlands.

SETTING: An increasing proportion of tuberculosis (TB) patients in low-incidence countries are immigrants. It is unclear whether contact investigations among immigrant patients are adequate. OBJECTIVE: To determine whether ethnicity of pulmonary TB patients was associated with coverage and yield of contact investigations in the Netherlands. DESIGN: Contact investigation results were extracted from records of patients reported in the nationwide surveillance register in 2006 and 2007. Prevalence odds ratios (PORs) with 95% confidence intervals (CIs) were calculated to determine the association between patient ethnicity and coverage of contact investigations and the yield of individuals with Mycobacterium tuberculosis infection or TB. RESULTS: Of the 1040 pulmonary TB patients reported, 642 (62%) were eligible for analysis. Compared to close contacts of Dutch patients, close contacts of immigrant patients were significantly less likely to be examined for TB (89% vs. 93%, POR 0.6, 95%CI 0.5-0.7) and infection (50% vs. 75%, POR 0.3, 95%CI 0.3-0.4), whereas the yield was significantly higher for disease (1.5% vs. 0.4%, POR 3.4, 95%CI 1.8-6.4) and infection (13% vs. 10%, POR 1.2, 95%CI 1.0-1.5). CONCLUSION: The effectiveness of contact investigations in the Netherlands can be optimised by expanding the investigation of contacts of immigrant patients.

Internal stresses, normal modes, and nonaffinity in three-dimensional biopolymer networks.

We numerically investigate deformations and modes of networks of semiflexible biopolymers as a function of crosslink coordination number z and strength of bending and stretching energies. In equilibrium filaments are under internal stress, and the networks exhibit shear rigidity below the Maxwell isostatic point. In contrast to two-dimensional networks, ours exhibit nonaffine bending-dominated response in all rigid states, including those near the maximum of z=4 when bending energies are less than stretching ones.

Semiflexible filamentous composites.

Inspired by the ubiquity of composite filamentous networks in nature, we investigate models of biopolymer networks that consist of interconnected floppy and stiff filaments. Numerical simulations carried out in three dimensions allow us to explore the microscopic partitioning of stresses and strains between the stiff and floppy fractions cs and cf and reveal a nontrivial relationship between the mechanical behavior and the relative fraction of stiff polymer: when there are few stiff polymers, nonpercolated stiff "inclusions" are protected from large deformations by an encompassing floppy matrix, while at higher fractions of stiff material the stiff network is independently percolated and dominates the mechanical response.

Frequency-dependent stiffening of semiflexible networks: a dynamical nonaffine to affine transition.

By combining the force-extension relation of single semiflexible polymers with a Langevin equation to capture the dissipative dynamics of chains moving through a viscous medium we study the dynamical response of cross-linked biopolymer materials. We find that at low frequencies the network deformations are highly nonaffine, and show a low plateau in the modulus. At higher frequencies, this nonaffinity decreases while the elastic modulus increases. With increasing frequency, more and more nonaffine network relaxation modes are suppressed, resulting in a stiffening. This effect is fundamentally different from the high-frequency stiffening due to the single-filament relaxation modes [F. Gittes and F. C. MacKintosh, Phys. Rev. E 58, R1241 (1998)], not only in terms of its mechanism but also in its resultant scaling: G'(ω) ∼ ω(α) with α > 3/4. This may determine nonlinear material properties at low, physiologically relevant frequencies.

Monte Carlo study of multiply crosslinked semiflexible polymer networks.

We present a method to generate realistic, three-dimensional networks of crosslinked semiflexible polymers. The free energy of these networks is obtained from the force-extension characteristics of the individual polymers and their persistent directionality through the crosslinks. A Monte Carlo scheme is employed to obtain isotropic, homogeneous networks that minimize the free energy and for which all of the relevant parameters can be varied: the persistence length and the contour length as well as the crosslinking length may be chosen at will. We also provide an initial survey of the mechanical properties of our networks subjected to shear strains, showing them to display the expected nonlinear stiffening behavior. Also, a key role for nonaffinity and its relation to order in the network is uncovered.

Three-dimensional cross-linked F-actin networks: relation between network architecture and mechanical behavior.

Numerical simulations are reported for the response of three-dimensional cross-linked F-actin networks when subjected to large deformations. In addition to the physiological parameters such as actin and cross-linker concentration, the model explicitly accounts for filament properties and network architecture. Complementary to two-dimensional studies, we find that the strain-stiffening characteristics depend on network architecture through the local topology around cross-links.