The effect of reinfection and mixed Trypanosoma cruzi infections on disease progression in mice

The progression of Chagas disease (CD) varies significantly from host to host and is affected by multiple factors. In particular, mixed strain infections and reinfections have the potential to exacerbate disease progression subsequently affecting clinical management of patients with CD. Consequently, an associated reduction in therapeutic intervention and poor prognosis may occur due to this exacerbated disease state. This study investigated the effects of mixed strain infections and reinfection with Trypanosoma cruzi in mice, using two isolates from different discrete typing units, TcI (C8 clone 1) and TcIV (10R26). There were no significant differences in mortality rate, body weight or body condition among mice infected with either C8 clone 1, 10R26, or a mixture of both isolates. However, the parasite was found in a significantly greater number of host organs in mice infected with a mixture of isolates, and the histopathological response to infection was significantly greater in mice infected with C8 clone 1 alone, and C8 clone 1 + 10R26 mixed infections than in mice infected with 10R26 alone. To investigate the effects of reinfection, mice received either a double exposure to C8 clone 1; a double exposure to 10R26; exposure to C8 clone 1 followed by 10R26; or exposure to 10R26 followed by C8 done 1. Compared to single infection groups, mortality was significantly increased, while survival time, body weight and body condition were all significantly decreased across all reinfection groups, with no significant differences among these groups. The mortality rate over all reinfection groups was 63.6%, compared to 0% in single infection groups, however there was no evidence of a greater histopathological response to infection. These results suggest firstly, that the C8 clone 1 isolate is more virulent than the 10R26 isolate, and secondly, that a more disseminated infection may occur with a mixture of isolates than with single isolates, although there is no evidence that mixed infections have a greater pathological effect. By contrast, reinfections do have major effects on host survivability and thus disease outcome. This confirms previous research demonstrating spontaneous deaths following reinfection, a phenomenon that to our knowledge has only been reported once before

Sentinel lymph node biopsy in esophageal cancer: an essential step towards individualized care

Lymph node status is the most important prognostic factor in esophageal cancer. Through improved detection of lymph node metastases, using the sentinel lymph node concept, accurate staging and more tailored therapy may be achieved. This review article outlines two principle ways in which the sentinel lymph node concept could dramatically influence current standard of care for patients with esophageal cancer. We discuss three limitations to universal acceptance of the technique, and propose next steps for increasing enthusiasm amongst physicians and surgeons including the development of a universal tracer, and improved contrast agents with novel dual-modality ‘visibility’.George L Balalis and Sarah K Thompso

A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia

Background. Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. Methods. Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. Results. During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. Conclusions. The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection

A data storage model for novel partial differential equation descretizations.

The purpose of this report is to define a standard interface for storing and retrieving novel, non-traditional partial differential equation (PDE) discretizations. Although it focuses specifically on finite elements where state is associated with edges and faces of volumetric elements rather than nodes and the elements themselves (as implemented in ALEGRA), the proposed interface should be general enough to accommodate most discretizations, including hp-adaptive finite elements and even mimetic techniques that define fields over arbitrary polyhedra. This report reviews the representation of edge and face elements as implemented by ALEGRA. It then specifies a convention for storing these elements in EXODUS files by extending the EXODUS API to include edge and face blocks in addition to element blocks. Finally, it presents several techniques for rendering edge and face elements using VTK and ParaView, including the use of VTK's generic dataset interface for interpolating values interior to edges and faces

Metabolite changes in blood predict the onset of tuberculosis

Immunogenetics and cellular immunology of bacterial infectious disease

A simple and efficient numerical scheme to integrate non-local potentials

As nuclear wave functions have to obey the Pauli principle, potentials issued from reaction theory or Hartree-Fock formalism using finite-range interactions contain a non-local part. Written in coordinate space representation, the Schrodinger equation becomes integro-differential, which is difficult to solve, contrary to the case of local potentials, where it is an ordinary differential equation. A simple and powerful method has been proposed several years ago, with the trivially equivalent potential method, where non-local potential is replaced by an equivalent local potential, which is state-dependent and has to be determined iteratively. Its main disadvantage, however, is the appearance of divergences in potentials if the wave functions have nodes, which is generally the case. We will show that divergences can be removed by a slight modification of the trivially equivalent potential method, leading to a very simple, stable and precise numerical technique to deal with non-local potentials. Examples will be provided with the calculation of the Hartree-Fock potential and associated wave functions of 16O using the finite-range N3LO realistic interaction.Comment: 8 pages, 2 figures, submitted to Eur. Phys. J.

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Anomalous NMR Magnetic Shifts in CeCoIn_5

We report ^{115}In and ^{59}Co Nuclear Magnetic Resonance (NMR) measurements in the heavy fermion superconductor CeCoIn_5 above and below T_c. The hyperfine couplings of the In and Co are anisotropic and exhibit dramatic changes below 50K due to changes in the crystal field level populations of the Ce ions. Below T_c the spin susceptibility is suppressed, indicating singlet pairing.Comment: 4 pages, 4 figure

Aging dynamics in a colloidal glass of Laponite

The aging dynamics of colloidal suspensions of Laponite, a synthetic clay, is investigated using dynamic light stattering (DLS) and viscometry after a quench into the glassy phase. DLS allows to follow the diffusion of Laponite particles and reveals that there are two modes of relaxation. The fast mode corresponds to a rapid diffusion of particles within "cages" formed by the neighboring particles. The slow mode corresponds to escape from the cages: its average relaxation time increases exponentially fast with the age of the glass. In addition, the slow mode has a broad distribution of relaxation times, its distribution becoming larger as the system ages. Measuring the concomitant increase of viscosity as the system ages, we can relate the slowing down of the particle dynamics to the viscosity.Comment: 9 pages, 8 Postscript figures, submitted to Phys. Rev.

The first multi-wavelength campaign of AXP 4U 0142+61 from radio to hard X-rays

For the first time a quasi-simultaneous multi-wavelength campaign has been performed on an Anomalous X-ray Pulsar from the radio to the hard X-ray band. 4U 0142+61 was an INTEGRAL target for 1 Ms in July 2005. During these observations it was also observed in the X-ray band with Swift and RXTE, in the optical and NIR with Gemini North and in the radio with the WSRT. In this paper we present the source-energy distribution. The spectral results obtained in the individual wave bands do not connect smoothly; apparently components of different origin contribute to the total spectrum. Remarkable is that the INTEGRAL hard X-ray spectrum (power-law index 0.79 +/- 0.10) is now measured up to an energy of ~230 keV with no indication of a spectral break. Extrapolation of the INTEGRAL power-law spectrum to lower energies passes orders of magnitude underneath the NIR and optical fluxes, as well as the low ~30 microJy (2 sigma) upper limit in the radio band.Comment: 6 pages, 1 figure. To be published in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 24-28, 2006, London, UK), eds. S. Zane, R. Turolla and D. Pag