Prediction of serotypes causing invasive pneumococcal disease in unvaccinated and vaccinated populations.

INTRODUCTION: Before the introduction of the heptavalent pneumococcal conjugate vaccine (Prevnar-7), the relative prevalence of serotypes of Streptococcus pneumoniae was fairly stable worldwide. We sought to develop a statistical tool to predict the relative frequency of different serotypes among disease isolates in the pre- and post-Prevnar-7 eras using the limited amount of data that is widely available. METHODS: We initially used pre-Prevnar-7 carriage prevalence and estimates of invasiveness derived from case-fatality data as predictors for the relative abundance of serotypes causing invasive pneumococcal disease during the pre- and post-Prevnar-7 eras, using negative binomial regression. We fit the model to pre-Prevnar-7 invasive pneumococcal disease data from England and Wales and used these data to (1) evaluate the performance of the model using several datasets and (2) evaluate the utility of the country-specific carriage data. We then fit an alternative model that used polysaccharide structure, a correlate of prevalence that does not require country-specific information and could be useful in determining the postvaccine population structure, as a predictor. RESULTS: Predictions from the initial model fit data from several pediatric populations in the pre-Prevnar-7 era. After the introduction of Prevnar-7, the model still had a good negative predictive value, though substantial unexplained variation remained. The alternative model had a good negative predictive value but poor positive predictive value. Both models demonstrate that the pneumococcal population follows a somewhat predictable pattern even after vaccination. CONCLUSIONS: This approach provides a preliminary framework to evaluate the potential patterns and impact of serotypes causing invasive pneumococcal disease

The Exozodiacal Dust Problem for Direct Observations of ExoEarths

Debris dust in the habitable zones of stars - otherwise known as exozodiacal dust - comes from extrasolar asteroids and comets and is thus an expected part of a planetary system. Background flux from the Solar System's zodiacal dust and the exozodiacal dust in the target system is likely to be the largest source of astrophysical noise in direct observations of terrestrial planets in the habitable zones of nearby stars. Furthermore, dust structures like clumps, thought to be produced by dynamical interactions with exoplanets, are a possible source of confusion. In this paper, we qualitatively assess the primary impact of exozodical dust on high-contrast direct imaging at optical wavelengths, such as would be performed with a coronagraph. Then we present the sensitivity of previous, current, and near-term facilities to thermal emission from debris dust at all distances from nearby solar-type stars, as well as our current knowledge of dust levels from recent surveys. Finally, we address the other method of detecting debris dust, through high-contrast imaging in scattered light. This method is currently far less sensitive than thermal emission observations, but provides high spatial resolution for studying dust structures. This paper represents the first report of NASA's Exoplanet Exploration Program Analysis Group (ExoPAG).Comment: 21 pages, 5 figures, 2 tables. Accepted for publication in PASP 2012-06-0

Estimating rates of carriage acquisition and clearance and competitive ability for pneumococcal serotypes in Kenya with a Markov transition model.

BACKGROUND: There are more than 90 serotypes of Streptococcus pneumoniae, with varying biologic and epidemiologic properties. Animal studies suggest that carriage induces an acquired immune response that reduces duration of colonization in a nonserotype-specific fashion. METHODS: We studied pneumococcal nasopharyngeal carriage longitudinally in Kenyan children 3-59 months of age, following up positive swabs at days 2, 4, 8, 16, and 32 and then monthly thereafter until 2 swabs were negative for the original serotype. As previously reported, 1868/2840 (66%) of children swabbed at baseline were positive. We estimated acquisition, clearance, and competition parameters for 27 serotypes using a Markov transition model. RESULTS: Point estimates of type-specific acquisition rates ranged from 0.00025/d (type 1) to 0.0031/d (type 19F). Point estimates of time to clearance (inverse of type-specific immune clearance rate) ranged from 28 days (type 20) to 124 days (type 6A). For the serotype most resistant to competition (type 19F), acquisition of other serotypes was 52% less likely (95% confidence interval = 37%-63%) than in an uncolonized host. Fitness components (carriage duration, acquisition rate, lack of susceptibility to competition) were positively correlated with each other and with baseline prevalence, and were associated with biologic properties previously shown to associate with serotype. Duration of carriage declined with age for most serotypes. CONCLUSIONS: Common S. pneumoniae serotypes appear superior in many dimensions of fitness. Differences in rate of immune clearance are attenuated as children age and become capable of more rapid clearance of the longest-lived serotypes. These findings provide information for comparison after introduction of pneumococcal conjugate vaccine

Concentric and eccentric endurance exercise reverse hallmarks of T-Cell senescence in pre-diabetic subjects

The peripheral T-cell pool undergoes a striking age associated remodeling which is accelerated by progressive insulin resistance. Exercise training is known to delay several aspects of T-cell senescence. The purpose of the current study was to investigate the effect of 3 weeks regular concentric or eccentric endurance exercise training on the composition of the T-cell compartment in pre-diabetic subjects. Sixteen male older adults with impaired glucose tolerance were recruited and performed either concentric exercise (CE) or eccentric exercise (EE) walking 3 times a week for 3 weeks. Fasting venous blood sampling was performed before training and after the training intervention. Various T-cell subpopulations were analyzed by flow cytometry. We did not find significant time × group effects (interaction) but found several significant time effects for cell type ratios and cell subsets proportions. There was an increase of the CD4+/CD8+ (0.55 ± 0.85%; p = 0.033) and CD4+/CD3+ ratio (5.63 ± 8.44%; p = 0.018) and a decrease of the CD8+/CD3+ ratio (-0.95 ± 1.64%; p = 0.049) after training. We found proportional increases of CD4+/CCR7+/CD45RO+ central memory cells (5.02 ± 7.68%; p = 0.030), naïve CD8+/CCR7+/CD45RO- (3.00 ± 6.68%; p = 0.047) and CD8+/CCR7+/CD45RO+ central memory cells (3.01 ± 3.70%; p = 0.009), while proportions of CD4+/CCR7-/CD45RO- TEMRA cells (-2.17 ± 4.66%; p = 0.012), CD8+/CCR7-/CD45RO- TEMRA cells (-5.11 ± 7.02%; p = 0.018) and CD16+ cells (-4.67 ± 6.45%; p = 0.016) decreased after training. 3 weeks of either CE or EE were effective in reversing hallmarks of T-cell senescence in pre-diabetic subjects. It is suggested that exercise stimulates production and mobilization of naïve T-cells, while differentiated TEMRA cells might disappear by apoptosis

Revealing Asymmetries in the HD181327 Debris Disk: A Recent Massive Collision or Interstellar Medium Warping

New multi-roll coronagraphic images of the HD181327 debris disk obtained using the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope reveal the debris ring in its entirety at high signal-to-noise ratio and unprecedented spatial resolution. We present and apply a new multi-roll image processing routine to identify and further remove quasi-static point-spread function-subtraction residuals and quantify systematic uncertainties. We also use a new iterative image deprojection technique to constrain the true disk geometry and aggressively remove any surface brightness asymmetries that can be explained without invoking dust density enhancements/ deficits. The measured empirical scattering phase function for the disk is more forward scattering than previously thought and is not well-fit by a Henyey-Greenstein function. The empirical scattering phase function varies with stellocentric distance, consistent with the expected radiation pressured-induced size segregation exterior to the belt. Within the belt, the empirical scattering phase function contradicts unperturbed debris ring models, suggesting the presence of an unseen planet. The radial profile of the flux density is degenerate with a radially varying scattering phase function; therefore estimates of the ring's true width and edge slope may be highly uncertain.We detect large scale asymmetries in the disk, consistent with either the recent catastrophic disruption of a body with mass greater than 1% the mass of Pluto, or disk warping due to strong interactions with the interstellar medium

Probing for Exoplanets Hiding in Dusty Debris Disks: Disk Imaging, Characterization, and Exploration with HST/STIS Multi-Roll Coronagraphy

Spatially resolved scattered-light images of circumstellar (CS) debris in exoplanetary systems constrain the physical properties and orbits of the dust particles in these systems. They also inform on co-orbiting (but unseen) planets, systemic architectures, and forces perturbing starlight-scattering CS material. Using HST/STIS optical coronagraphy, we have completed the observational phase of a program to study the spatial distribution of dust in ten CS debris systems, and one "mature" protoplanetrary disk all with HST pedigree, using PSF-subtracted multi-roll coronagraphy. These observations probe stellocentric distances > 5 AU for the nearest stars, and simultaneously resolve disk substructures well beyond, corresponding to the giant planet and Kuiper belt regions in our Solar System. They also disclose diffuse very low-surface brightness dust at larger stellocentric distances. We present new results inclusive of fainter disks such as HD92945 confirming, and better revealing, the existence of a narrow inner debris ring within a larger diffuse dust disk. Other disks with ring-like sub-structures, significant asymmetries and complex morphologies include: HD181327 with a posited spray of ejecta from a recent massive collision in an exo-Kuiper belt; HD61005 suggested interacting with the local ISM; HD15115 & HD32297, discussed also in the context of environmental interactions. These disks, and HD15745, suggest debris system evolution cannot be treated in isolation. For AU Mic's edge-on disk, out-of-plane surface brightness asymmetries at > 5 AU may implicate one or more planetary perturbers. Time resolved images of the MP Mus proto-planetary disk provide spatially resolved temporal variability in the disk illumination. These and other new images from our program enable direct inter-comparison of the architectures of these exoplanetary debris systems in the context of our own Solar System.Comment: 109 pages, 43 figures, accepted for publication in the Astronomical Journa

Increased Turnover of T Lymphocytes in HIV-1 Infection and Its Reduction by Antiretroviral Therapy

The mechanism of CD4+ T cell depletion in human immunodeficiency virus (HIV)-1 infection remains controversial. Using deuterated glucose to label the DNA of proliferating cells in vivo, we studied T cell dynamics in four normal subjects and seven HIV-1–infected patients naive to antiretroviral drugs. The results were analyzed using a newly developed mathematical model to determine fractional rates of lymphocyte proliferation and death. In CD4+ T cells, mean proliferation and death rates were elevated by 6.3- and 2.9-fold, respectively, in infected patients compared with normal controls. In CD8+ T cells, the mean proliferation rate was 7.7-fold higher in HIV-1 infection, but the mean death rate was not significantly increased. Five of the infected patients underwent subsequent deuterated glucose labeling studies after initiating antiretroviral therapy. The lymphocyte proliferation and death rates in both CD4+ and CD8+ cell populations were substantially reduced by 5–11 weeks and nearly normal by one year. Taken together, these new findings strongly indicate that CD4+ lymphocyte depletion seen in AIDS is primarily a consequence of increased cellular destruction, not decreased cellular production