Computerized epidemiological model of typhoid fever with age structure and its use in the planning and evaluation of antityphoid immunization and sanitation programmes

AbstractAn epidemiological model of typhoid fever[1] was further developed. Age structure was added to the population dynamics, but nonessential epidemiological classes were eliminated. Thus the dynamics of the disease in specific age groups can be studied, and the effect of public health interventions in these groups simulated. The model is based on the natural history of the disease and represents the multistate epidemiological structure which is fully computerised. It enables simulation of endemic processes in the various age groups of the population and the effects of control measures such as immunization and/or sanitation on the natural course of infection in various age strata of the population. In view that typhoid fever is a public health problem primarily in endemic areas of developing countries, the examples of model applications are related to such situations. The similation of the effectiveness of immunization and sanitation programmes are confined to the endemic conditions in such countries. The construction and the structure of the model are fully described. The computer program system is given in the Appendix, and the article provides all relevant information necessary for the use of the model for public health purposes

Supersymmetric NLO QCD Corrections to Resonant Slepton Production and Signals at the Tevatron and the LHC

We compute the total cross section and the transverse momentum distribution for single charged slepton and sneutrino production at hadronic colliders including NLO supersymmetric and non-supersymmetric QCD corrections. The supersymmetric QCD corrections can be substantial. We also resum the gluon transverse momentum distribution and compare our results with two Monte Carlo generators. We compute branching ratios of the supersymmetric decays of the slepton and determine event rates for the like-sign dimuon final state at the Tevatron and at the LHC.Comment: 14 pages, LaTeX, 8 figures, uses REVTex

T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes

Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10–15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function

Compact Frontend-Electronics and Bidirectional 3.3 Gbps Optical Datalink for Fast Proportional Chamber Readout

The 9600 channels of the multi-wire proportional chamber of the H1 experiment at HERA have to be read out within 96 ns and made available to the trigger system. The tight spatial conditions at the rear end flange require a compact bidirectional readout electronics with minimal power consumption and dead material. A solution using 40 identical optical link modules, each transferring the trigger information with a physical rate of 4 x 832 Mbps via optical fibers, has been developed and commisioned. The analog pulses from the chamber can be monitored and the synchronization to the global HERA clock signal is ensured.Comment: 13 pages, 10 figure

Research Proposal for an Experiment to Search for the Decay {\mu} -> eee

We propose an experiment (Mu3e) to search for the lepton flavour violating decay mu+ -> e+e-e+. We aim for an ultimate sensitivity of one in 10^16 mu-decays, four orders of magnitude better than previous searches. This sensitivity is made possible by exploiting modern silicon pixel detectors providing high spatial resolution and hodoscopes using scintillating fibres and tiles providing precise timing information at high particle rates.Comment: Research proposal submitted to the Paul Scherrer Institute Research Committee for Particle Physics at the Ring Cyclotron, 104 page

Using detergent to enhance detection sensitivity of African trypanosomes in human CSF and blood by Loop-Mediated Isothermal Amplification (LAMP)

<p><b>Background:</b> The loop-mediated isothermal amplification (LAMP) assay, with its advantages of simplicity, rapidity and cost effectiveness, has evolved as one of the most sensitive and specific methods for the detection of a broad range of pathogenic microorganisms including African trypanosomes. While many LAMP-based assays are sufficiently sensitive to detect DNA well below the amount present in a single parasite, the detection limit of the assay is restricted by the number of parasites present in the volume of sample assayed; i.e. 1 per µL or 103 per mL. We hypothesized that clinical sensitivities that mimic analytical limits based on parasite DNA could be approached or even obtained by simply adding detergent to the samples prior to LAMP assay.</p> <p><b>Methodology/Principal Findings:</b> For proof of principle we used two different LAMP assays capable of detecting 0.1 fg genomic DNA (0.001 parasite). The assay was tested on dilution series of intact bloodstream form Trypanosoma brucei rhodesiense in human cerebrospinal fluid (CSF) or blood with or without the addition of the detergent Triton X-100 and 60 min incubation at ambient temperature. With human CSF and in the absence of detergent, the LAMP detection limit for live intact parasites using 1 µL of CSF as the source of template was at best 103 parasites/mL. Remarkably, detergent enhanced LAMP assay reaches sensitivity about 100 to 1000-fold lower; i.e. 10 to 1 parasite/mL. Similar detergent-mediated increases in LAMP assay analytical sensitivity were also found using DNA extracted from filter paper cards containing blood pretreated with detergent before card spotting or blood samples spotted on detergent pretreated cards.</p> <p><b>Conclusions/Significance:</b> This simple procedure for the enhanced detection of live African trypanosomes in biological fluids by LAMP paves the way for the adaptation of LAMP for the economical and sensitive diagnosis of other protozoan parasites and microorganisms that cause diseases that plague the developing world.</p&gt