Comparison of model predictions of typhoid conjugate vaccine public health impact and cost-effectiveness

Models are useful to inform policy decisions on typhoid conjugate vaccine (TCV) deployment in endemic settings. However, methodological choices can influence model-predicted outcomes. To provide robust estimates for the potential public health impact of TCVs that account for structural model differences, we compared four dynamic and one static mathematical model of typhoid transmission and vaccine impact. All models were fitted to a common dataset of age-specific typhoid fever cases in Kolkata, India. We evaluated three TCV strategies: no vaccination, routine vaccination at 9 months of age, and routine vaccination at 9 months with a one-time catch-up campaign (ages 9 months to 15 years). The primary outcome was the predicted percent reduction in symptomatic typhoid cases over 10 years after vaccine introduction. For three models with economic analyses (Models A-C), we also compared the incremental cost-effectiveness ratios (ICERs), calculated as the incremental cost (US$) per disability-adjusted life-year (DALY) averted. Routine vaccination was predicted to reduce symptomatic cases by 10-46$95-789 per DALY averted; two models predicted the ICER of routine vaccination alone to be greater than with the addition of catch-up campaign. Despite differences in model-predicted vaccine impact and cost-effectiveness, routine vaccination plus a catch-up campaign is likely to be impactful and cost-effective in high incidence settings such as Kolkata

Comparison of Spectra in Unsequenced Species

International audienceWe introduce a new algorithm for the mass spectromet- ric identication of proteins. Experimental spectra obtained by tandem MS/MS are directly compared to theoretical spectra generated from pro- teins of evolutionarily closely related organisms. This work is motivated by the need of a method that allows the identication of proteins of unsequenced species against a database containing proteins of related organisms. The idea is that matching spectra of unknown peptides to very similar MS/MS spectra generated from this database of annotated proteins can lead to annotate unknown proteins. This process is similar to ortholog annotation in protein sequence databases. The difficulty with such an approach is that two similar peptides, even with just one mod- ication (i.e. insertion, deletion or substitution of one or several amino acid(s)) between them, usually generate very dissimilar spectra. In this paper, we present a new dynamic programming based algorithm: Packet- SpectralAlignment. Our algorithm is tolerant to modications and fully exploits two important properties that are usually not considered: the notion of inner symmetry, a relation linking pairs of spectrum peaks, and the notion of packet inside each spectrum to keep related peaks together. Our algorithm, PacketSpectralAlignment is then compared to SpectralAlignment [1] on a dataset of simulated spectra. Our tests show that PacketSpectralAlignment behaves better, in terms of results and execution tim

Estimating the effect of vaccination on antimicrobial-resistant typhoid fever in 73 countries supported by Gavi: a mathematical modelling study

BACKGROUND: Multidrug resistance and fluoroquinolone non-susceptibility (FQNS) are major concerns for the epidemiology and treatment of typhoid fever. The 2018 prequalification of the first typhoid conjugate vaccine (TCV) by WHO provides an opportunity to limit the transmission and burden of antimicrobial-resistant typhoid fever. METHODS: We combined output from mathematical models of typhoid transmission with estimates of antimicrobial resistance from meta-analyses to predict the burden of antimicrobial-resistant typhoid fever across 73 lower-income countries eligible for support from Gavi, the Vaccine Alliance. We considered FQNS and multidrug resistance separately. The effect of vaccination was predicted on the basis of forecasts of vaccine coverage. We explored how the potential effect of vaccination on the prevalence of antimicrobial resistance varied depending on key model parameters. FINDINGS: The introduction of routine immunisation with TCV at age 9 months with a catch-up campaign up to age 15 years was predicted to avert 46-74% of all typhoid fever cases in 73 countries eligible for Gavi support. Vaccination was predicted to reduce the relative prevalence of antimicrobial-resistant typhoid fever by 16% (95% prediction interval [PI] 0-49). TCV introduction with a catch-up campaign was predicted to avert 42.5 million (95% PI 24.8-62.8 million) cases and 506 000 (95% PI 187 000-1.9 million) deaths caused by FQNS typhoid fever, and 21.2 million (95% PI 16.4-26.5 million) cases and 342 000 (95% PI 135 000-1.5 million) deaths from multidrug-resistant typhoid fever over 10 years following introduction. INTERPRETATION: Our results indicate the benefits of prioritising TCV introduction for countries with a high avertable burden of antimicrobial-resistant typhoid fever. FUNDING: The Bill & Melinda Gates Foundation

Dissociation constants and thermodynamic properties of amino acids used in CO2 absorption from (293 to 353) K

The second dissociation constants of the amino acids βalanine, taurine, sarcosine, 6-aminohexanoic acid, DL-methionine, glycine, L-phenylalanine, and L-proline and the third dissociation constants of L-glutamic acid and L-aspartic acid have been determined from electromotive force measurements at temperatures from (293 to 353) K. Experimental results are reported and compared to literature values. Values of the standard state thermodynamic properties are derived from the experimental results and compared to the values of commercially available amines used as absorbents for CO 2 capture.

Search for the Production of Element 112 in the 48Ca + 238U Reaction

We have searched for the production of element 112 in the reaction of 231 MeV 48Ca with 238U. We have not observed any events with a "one event" upper limit cross section of 1.6 pb for EVR-fission events and 1.8 pb for EVR-alpha events.Comment: 6 pages, 3 figures, submitted to Phys. Rev.

Thermodynamics of Electrolytes on Anisotropic Lattices

The phase behavior of ionic fluids on simple cubic and tetragonal (anisotropic) lattices has been studied by grand canonical Monte Carlo simulations. Systems with both the true lattice Coulombic potential and continuous-space $1/r$ electrostatic interactions have been investigated. At all degrees of anisotropy, only coexistence between a disordered low-density phase and an ordered high-density phase with the structure similar to ionic crystal was found, in contrast to recent theoretical predictions. Tricritical parameters were determined to be monotonously increasing functions of anisotropy parameters which is consistent with theoretical calculations based on the Debye-H\"uckel approach. At large anisotropies a two-dimensional-like behavior is observed, from which we estimated the dimensionless tricritical temperature and density for the two-dimensional square lattice electrolyte to be $T^*_{tri}=0.14$ and $\rho^*_{tri} = 0.70$.Comment: submitted to PR

Classical-to-critical crossovers from field theory

We extent the previous determinations of nonasymptotic critical behavior of Phys. Rev B32, 7209 (1985) and B35, 3585 (1987) to accurate expressions of the complete classical-to-critical crossover (in the 3-d field theory) in terms of the temperature-like scaling field (i.e., along the critical isochore) for : 1) the correlation length, the susceptibility and the specific heat in the homogeneous phase for the n-vector model (n=1 to 3) and 2) for the spontaneous magnetization (coexistence curve), the susceptibility and the specific heat in the inhomogeneous phase for the Ising model (n=1). The present calculations include the seventh loop order of Murray and Nickel (1991) and closely account for the up-to-date estimates of universal asymptotic critical quantities (exponents and amplitude combinations) provided by Guida and Zinn-Justin [J. Phys. A31, 8103 (1998)].Comment: 4 figs, 4 program documents in appendix, some corrections adde

Reexamination of the long-range Potts model: a multicanonical approach

We investigate the critical behavior of the one-dimensional q-state Potts model with long-range (LR) interaction $1/r^{d+\sigma}$, using a multicanonical algorithm. The recursion scheme initially proposed by Berg is improved so as to make it suitable for a large class of LR models with unequally spaced energy levels. The choice of an efficient predictor and a reliable convergence criterion is discussed. We obtain transition temperatures in the first-order regime which are in far better agreement with mean-field predictions than in previous Monte Carlo studies. By relying on the location of spinodal points and resorting to scaling arguments, we determine the threshold value $\sigma_c(q)$ separating the first- and second-order regimes to two-digit precision within the range $3 \leq q \leq 9$. We offer convincing numerical evidence supporting $\sigma_c(q)Comment: 18 pages, 18 figure

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors