Effect of Mass Supplementation with Ready-to-Use Supplementary Food during an anticipated nutritional emergency

Previous studies have shown the benefits of ready-to-use supplementary food (RUSF) distribution in reducing the incidence and prevalence of severe acute malnutrition

Superior T memory stem cell persistence supports long-lived T cell memory

Long-lived memory T cells are able to persist in the host in the absence of antigen; however, the mechanism by which they are maintained is not well understood. Recently, a subset of human T cells, stem cell memory T cells (TSCM cells), was shown to be self-renewing and multipotent, thereby providing a potential reservoir for T cell memory throughout life. However, their in vivo dynamics and homeostasis still remain to be defined due to the lack of suitable animal models. We identified T cells with a TSCM phenotype and stem cell–like properties in nonhuman primates. These cells were the least-differentiated memory subset, were functionally distinct from conventional memory cells, and served as precursors of central memory. Antigen-specific TSCM cells preferentially localized to LNs and were virtually absent from mucosal surfaces. They were generated in the acute phase of viral infection, preferentially survived in comparison with all other memory cells following elimination of antigen, and stably persisted for the long term. Thus, one mechanism for maintenance of long-term T cell memory derives from the unique homeostatic properties of TSCM cells. Vaccination strategies designed to elicit durable cellular immunity should target the generation of TSCM cells

Performance of Small Cluster Surveys and the Clustered LQAS Design to estimate Local-level Vaccination Coverage in Mali

<p>Abstract</p> <p>Background</p> <p>Estimation of vaccination coverage at the local level is essential to identify communities that may require additional support. Cluster surveys can be used in resource-poor settings, when population figures are inaccurate. To be feasible, cluster samples need to be small, without losing robustness of results. The clustered LQAS (CLQAS) approach has been proposed as an alternative, as smaller sample sizes are required.</p> <p>Methods</p> <p>We explored (i) the efficiency of cluster surveys of decreasing sample size through bootstrapping analysis and (ii) the performance of CLQAS under three alternative sampling plans to classify local VC, using data from a survey carried out in Mali after mass vaccination against meningococcal meningitis group A.</p> <p>Results</p> <p>VC estimates provided by a 10 × 15 cluster survey design were reasonably robust. We used them to classify health areas in three categories and guide mop-up activities: i) health areas not requiring supplemental activities; ii) health areas requiring additional vaccination; iii) health areas requiring further evaluation. As sample size decreased (from 10 × 15 to 10 × 3), standard error of VC and ICC estimates were increasingly unstable. Results of CLQAS simulations were not accurate for most health areas, with an overall risk of misclassification greater than 0.25 in one health area out of three. It was greater than 0.50 in one health area out of two under two of the three sampling plans.</p> <p>Conclusions</p> <p>Small sample cluster surveys (10 × 15) are acceptably robust for classification of VC at local level. We do not recommend the CLQAS method as currently formulated for evaluating vaccination programmes.</p

A density-temperature description of the outer electron radiation belt during geomagnetic storms

Bi-Maxwellian fits are made to energetic-electron flux measurements from seven satellites in geosynchronous orbit, yielding a number density (n) and temperature (T) description of the outer electron radiation belt. For 54.5 spacecraft years of measurements the median value of n is 3.7 × 10−4 cm−3, and the median value of T is 148 keV. General statistical properties of n, T, and the 1.1–1.5 MeV flux F are investigated, including local-time and solar-cycle dependencies. Using superposed-epoch analysis where the zero epoch is convection onset, the evolution of the outer electron radiation belt through high-speed-stream-driven storms is investigated. The number-density decay during the calm before the storm, relativistic-electron dropouts and recoveries, and the heating of the outer electron radiation belt during storms are analyzed. Using four different “triggers” (sudden storm commencement (SSC), southward interplanetary magnetic field (IMF) portions of coronal mass ejection (CME) sheaths, southward-IMF portions of magnetic clouds, and minimum Dst) a selection of CME-driven storms are analyzed with superposed-epoch techniques. For CME-driven storms, only a very modest density decay prior to storm onset is found. In addition, the compression of the outer electron radiation belt at the time of SSC is analyzed, the number-density increase and temperature decrease during storm main phase are characterized, and the increase in density and temperature during storm recovery phase is determined. During the different phases of storms, changes in the flux are sometimes in response to changes in the temperature, sometimes to changes in the number density, and sometimes to changes in both. Differences are found between the density-temperature and flux descriptions, and it is concluded that more information is available using the density-temperature description

Lithium abundances in CEMP stars

Carbon-enhanced metal-poor (CEMP) stars are believed to show the chemical imprints of more massive stars (M > 0.8 Msun) that are now extinct. In particular, it is expected that the observed abundance of Li should deviate in these stars from the standard Spite lithium plateau. We study here a sample of 11 metal-poor stars and a double-lined spectroscopic binary with -1.8 <[Fe/H]< -3.3 observed with VLT/UVES spectrograph. Among these 12 metal-poor stars, there are 8 CEMP stars for which we measure or constrain the Li abundance. In contrast to previous arguments, we demonstrate that an appropriate regime of dilution permits the existence of "Li-Spite plateau and C-rich" stars, whereas some of the "Li-depleted and C-rich" stars call for an unidentified additional depletion mechanism that cannot be explained by dilution alone. We find evidence that rotation is related to the Li depletion in some CEMP stars. Additionally, we report on a newly recognized double-lined spectroscopic binary star in our sample. For this star, we develop a new technique from which estimates of stellar parameters and luminosity ratios can be derived based on a high-resolution spectrum alone, without the need for input from evolutionary models.Comment: 62 pages, 16 figures, accepted for publication in Ap

Immunization with apical membrane antigen 1 confers sterile infection-blocking immunity against Plasmodium sporozoite challenge in a rodent model

Apical membrane antigen 1 (AMA-1) is a leading blood-stage malaria vaccine candidate. Consistent with a key role in erythrocytic invasion, AMA-1-specific antibodies have been implicated in AMA-1-induced protective immunity. AMA-1 is also expressed in sporozoites and in mature liver schizonts where it may be a target of protective cell-mediated immunity. Here, we demonstrate for the first time that immunization with AMA-1 can induce sterile infection-blocking immunity against Plasmodium sporozoite challenge in 80% of immunized mice. Significantly higher levels of gamma interferon (IFN-γ)/interleukin-2 (IL-2)/tumor necrosis factor (TNF) multifunctional T cells were noted in immunized mice than in control mice. We also report the first identification of minimal CD8 and CD4 T cell epitopes on Plasmodium yoelii AMA-1. These data establish AMA-1 as a target of both preerythrocytic- and erythrocytic-stage protective immune responses and validate vaccine approaches designed to induce both cellular and humoral immunity

Parliamentary co-evolution: national parliamentary reactions to the empowerment of the European Parliament

Existing research on the European Union's (EU) multilevel parliamentary system builds on the hypothesis of parallel evolution, situating explanations for European Parliament (EP) empowerment at the EU level and explanations for national parliamentary powers in EU affairs at the national level. We propose the hypothesis of co-evolution, which specifies a connection between national and European arenas of parliamentarization. We study whether the EP's empowerment enhances or reduces pressure on national parliaments to strengthen their own EU-related competences. First, we argue that national parliamentary parties take conscious positions on the powers of the EP. Second, support for the EP among the party composition of national parliaments tells us whether parliaments regard the EP as a competitor or ally, feeling pressed, or relieved of the pressure, to strengthen their EU-related competences

Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes

Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naïve T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter- and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design. © 2013 Nascimento et al

Cancer immunoprevention and public health

The power of cancer immune surveillance has been documented beyond doubt, and the successful exploitation of immune response to cancer has started a new era in the war against cancer. Cancer biologists have recognized immunoevasion as an emerging hallmark in addition to the six hallmarks of cancer. Besides the natural connection between the immune system and cancer development, most established environmental risk factors are now known to interfere with immune surveillance mechanisms. Genetic variations regulating immunity may also modulate cancer susceptibility, but evidence for this is currently limited. Molecular cross talk linking “immune” and “genomic” surveillance pathways has been characterized. It appears that immune mechanisms may contribute to the effects of common cancer risk factors. We provide an updated overview of evidence for cancer immune surveillance, cancer risk factors interfering with it, and interventions to enhance cancer immune surveillance as tools to complement ongoing vaccine development efforts for cancer immunoprevention. Although there is a lot of support for cancer immunoprevention with simple lifestyle modifications from observational studies, there is an urgent need for clinical trials to establish the effectiveness of this approach for public health benefits

COMPASS identifies T-cell subsets correlated with clinical outcomes.

Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells as well as the interrogation of cell population heterogeneity. However, in many instances, computational tools to analyze the wealth of data generated by these technologies are lacking. Here, we present a computational framework for unbiased combinatorial polyfunctionality analysis of antigen-specific T-cell subsets (COMPASS). COMPASS uses a Bayesian hierarchical framework to model all observed cell subsets and select those most likely to have antigen-specific responses. Cell-subset responses are quantified by posterior probabilities, and human subject-level responses are quantified by two summary statistics that describe the quality of an individual's polyfunctional response and can be correlated directly with clinical outcome. Using three clinical data sets of cytokine production, we demonstrate how COMPASS improves characterization of antigen-specific T cells and reveals cellular 'correlates of protection/immunity' in the RV144 HIV vaccine efficacy trial that are missed by other methods. COMPASS is available as open-source software