Properties of an entropy-based signal receiver with an application to ultrasonic molecular imaging.

Qualitative and quantitative properties of the finite part, H(f), of the Shannon entropy of a continuous waveform f(t) in the continuum limit are derived in order to illuminate its use for waveform characterization. Simple upper and lower bounds on H(f), based on features of f(t), are defined. Quantitative criteria for a priori estimation of the average-case variation of H(f) and log E(f), where E(f) is the signal energy of f(t) are also derived. These provide relative sensitivity estimates that could be used to prospectively choose optimal imaging strategies in real-time ultrasonic imaging machines, where system bandwidth is often pushed to its limits. To demonstrate the utility of these sensitivity relations for this application, a study designed to assess the feasibility of identification of angiogenic neovasculature targeted with perfluorocarbon nanoparticles that specifically bind to alpha(v)beta3-integrin expression in tumors was performed. The outcome of this study agrees with the prospective sensitivity estimates that were used for the two receivers. Moreover, these data demonstrate the ability of entropy-based signal receivers when used in conjunction with targeted nanoparticles to elucidate the presence of alpha(v)beta3 integrins in primordial neovasculature, particularly in acoustically unfavorable environments.

Transmural variation of myocardial attenuation and its potential effect on contrast-mediated estimates of regional myocardial perfusion.

Promising technical developments suggest that it may be feasible to use contrast echocardiography to estimate regional myocardial perfusion. Although the optimal approach has not yet been determined, the use of a nonlinear (harmonic) response of the contrast agent is common to several recent advances. The purpose of this article is to delineate the relation between the anisotropic (angle-dependent) ultrasonic attenuation of the myocardium through which the sound wave has propagated and the regional, nonlinear response of the contrast agent. Apparent perfusion will be modulated by this regionally varying, path-dependent attenuation, which is determined by the local angle between the propagating sound wave and the myofiber orientation. We illustrate the potential magnitude of the effect of myocardial anisotropy for the apical 4-chamber view by examining propagation along the septum and the lateral wall. We present experimentally measured values of the attenuation of excised sheep myocardium, showing statistically significant differences in the attenuation in the mid wall compared with that in symmetrical zones to the left and right of the mid wall, reflecting the well-known myofiber orientations in these 3 regions. The nonlinear (harmonic) response of a contrast agent depends on the local pressure amplitude, which for a given mechanical index is determined by the attenuation accumulated along the path to the point where the regional perfusion is estimated.

Transmural variation of myocardial attenuation measured with a clinical imager.

The objective of this study was to quantify the transmural variation in attenuation for the septal and lateral walls of the heart. Our approach was to utilize a commercially available ultrasonic imaging system to acquire images of excised sections of eight sheep hearts with an orientation similar to that encountered in the apical four-chamber view. The measured values (mean +/-SE) of the slope of attenuation for the transmural regions of the septum are: 1.40 +/-0.11, 0.99 +/-0.09, and 1.85 +/-0.16 (dB/cm/MHz) for the left subendocardial, midmyocardial, and right subendocardial zones, respectively. The analogous data from the lateral wall are: 1.42 +/-0.11, 0.83 +/-0.07, and 1.20 +/- 0.16 (dB/cm/MHz) for the subendocardial, midmyocardial, and subepicardial zones, respectively. These data demonstrate that ultrasonic attenuation associated with the septum and the lateral wall, when imaged in a manner similar to that of the apical four-chamber view, is anisotropic.

Immunogenicity and protective efficacy of DNA vaccines encoding secreted and non-secreted forms of Mycobacterium tuberculosis Ag85A.

OBJECTIVE: To determine the efficacy of Ag85A-DNA against challenge with a highly virulent human clinical isolate of Mycobacterium tuberculosis (CSU37) and to compare the potencies of two types of Ag85A-DNA vaccines; those expressing secreted and non-secreted forms of the protein. DESIGN: Ag85A-DNA vaccinated mice were challenged with a highly virulent clinical isolate of M. tuberculosis (CSU37) in order to compare the efficacy of these vaccines. In vitro studies were also performed. RESULTS: Enhanced humoral and cellular responses were induced in mice vaccinated with the secreted Ag85A-DNA compared to the non-secreted Ag85A-DNA. In addition, secreted Ag85A-DNA conferred protective immunity against infection with M. tuberculosis (CSU37). CONCLUSIONS: DNA vaccines encoding M. tuberculosis Ag85A have been shown to induce potent humoral and cellular immune responses leading to protection from M. tuberculosis (Erdman) challenge in mouse models. In this study we demonstrate that Ag85A can confer protection in a rigorous challenge model using a highly virulent human clinical isolate of M. tuberculosis (CSU37). This challenge model appears able to discriminate between DNA vaccines of differing potencies, as the more immunogenic DNA construct encoding a secreted form of Ag85A was protective, whereas the less immunogenic DNA construct encoding a non-secreted form of Ag85A was not.

Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis.

The results of this study provide the first evidence that two completely separate vaccine approaches, one based on a subunit vaccine consisting of a mild adjuvant admixed with purified culture filtrate proteins and enhanced by the cytokine interleukin-2 and the second based on immunization with DNA encoding the Ag85A protein secreted by Mycobacterium tuberculosis, could both prevent the onset of caseating disease, which is the hallmark of the guinea pig aerogenic infection model. In both cases, however, the survival of vaccinated guinea pigs was shorter than that conferred by Mycobacterium bovis BCG, with observed mortality of these animals probably due to consolidation of lung tissues by lymphocytic granulomas. An additional characteristic of these approaches was that neither induced skin test reactivity to commercial tuberculin. These data thus provide optimism that development of nonliving vaccines which can generate long-lived immunity approaching that conferred by the BCG vaccine is a feasible goal.

Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae.

A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-gamma) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-gamma. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.

Relationship between household access to food and malnutrition in eastern and southern Africa.

This review paper gives an overview of the relationship between household access to food and malnutrition using national level data in the Eastern and Southern Africa Region. The overall prevalence of malnutrition amongst the under-five population have not changed significantly over the decade and, in some cases, have deteriorated. The situation of household access to food differs between economies and production systems, but most households (average of 80%) in the region do not have access to adequate food. A preliminary analysis of the determinants of malnutrition at country level pointed to the importance of: financial access to food (an indicator of household access to food) and; access to safe water (an indicator of household healthy environment), as the most significant variables predicting rates of malnutrition. Several areas for action by governments in the region and for further study within the subject of household access to food are delineated. These are: more clear determination of the relative contribution of household access to food, to the nutritional status of women and children and, improved analysis of indicators of household access to food.