Infection-acquired versus vaccine-acquired immunity in an SIRWS model

Despite high vaccine coverage, pertussis has re-emerged as a public health concern in many countries. One hypothesis posed for re-emergence is the waning of immunity. In some disease systems, the process of waning immunity can be non-linear, involving a complex relationship between the duration of immunity and subsequent boosting of immunity through asymptomatic re-exposure. We present and analyse a model of infectious disease transmission to examine the interplay between infection and immunity. By allowing the duration of infection-acquired immunity to differ from that of vaccine-acquired immunity, we explore the impact of the difference in durations on long-term disease patterns and prevalence of infection. Our model demonstrates that vaccination may induce cyclic behaviour, and its ability to reduce the infection prevalence increases with both the duration of infection-acquired immunity and duration of vaccine-acquired immunity. We find that increasing vaccine coverage, while capable of leading to an increase in overall transmission, always results in a reduction in prevalence of primary infections, with epidemic cycles characterised by a longer interepidemic period and taller peaks. Our results show that the epidemiological patterns of an infectious disease may change considerably when the duration of vaccine-acquired immunity differs from that of infection-acquired immunity. Our study highlights that for any particular disease and associated vaccine, a detailed understanding of the duration of protection and how that duration is influenced by infection prevalence is important as we seek to optimise vaccination strategies.Comment: 21 pages, 5 figure

Novel metal-film configuration: Rh on Ag(100)

We present the results of an investigation of Rh films on Ag(100). The films are studied using Auger-electron spectroscopy, low-energy electron diffraction, x-ray photoelectron spectroscopy, ultraviolet photoemission spectroscopy, ion-scattering spectroscopy, and scanning Auger microscopy. Overlayer characteristics are examined at substrate temperatures of 300 and 600 K. We find that the equilibrium configuration is not predicted by any of the three traditional growth modes (Frank–Van der Merwe, Stranski-Krastanov, or Volmer-Weber). Rather, the equilibrium film structure is that of a Ag-Rh-Ag sandwich, most probably flat. Formation of the sandwich is thermodynamically driven by the difference in surface free energies between Ag and Rh, and is kinetically accessible because of the high mobility of the Ag atoms

An electron-stimulated desorption ion angular distribution and low-energy electron diffraction investigation of CF3I on Ru(001)

We have investigated the structures of CF3I, and its dissociation products, adsorbed on Ru(001) using low-energy electron diffraction and electron-stimulated desorption ion angular distribution (ESDIAD). Atomic iodine forms (√3x√3)R30° islands even at very low coverages. At 70% of saturation and above, a (2X2) superstructure forms which we attribute to a p(2X2) unit cell with one CF3 group and one iodine atom. ESDIAD images show F+ desorbing at normal emission and in three hexagonal patterns. The normal emission is attributed to a tilted configuration of CF3(ad) in which one C-F bond is oriented perpendicular to the surface. A small hexagon is attributed to F(ad) on step edges. A large hexagon at low coverages may arise from isolated CF3(ad) species possessing C3v symmetry. And finally, an intermediate hexagon is attributed to perturbation of the CF3(ad) orientation by molecular fragments which result from electron irradiation of physisorbed CF3I

Identification of reconstruction in Pt films deposited on Pd(110) at room temperature

We have studied the properties of Pt films on Pd(110), grown by deposition at 300 K and annealed up to 900 K, using low-energy electron diffraction and Auger-electron spectroscopy. We observe (1×2) and (1×3) superstructures, depending upon Pt coverage and annealing temperature. At one monolayer, the (1×1) periodicity is unperturbed. Between one and three monolayers, a broad and streaky (1×2) develops upon annealing, then fades to (1×1) as the film dissolves. At three monolayers and above, the broad and streaky (1×2) splits to a (1×3), then fades again to (1×1) at high temperature. Adsorption of CO causes (1×3)→(1×1) reversion at relatively low temperature, 430 K. Based upon the known behavior of Pt(110) reconstructions, this is strong evidence that the (1×3) structure of the Pt film is a surface reconstruction

Camptothecin-based dendrimersomes for gene delivery and redox-responsive drug delivery to cancer cells

Combination therapy involving chemotherapeutic drugs and genes is emerging as a promising strategy to provide a synergistic therapeutic effect, to overcome drug resistance while reducing the severe side effects associated with conventional chemotherapeutic drugs. However, the lack of nanomedicines able to simultaneously carry anti-cancer drugs and nucleic acids limits the application of this therapeutic strategy. To overcome this issue, we proposed to synthesize a pro-drug dendrimer by conjugating the PEGylated, positively charged generation 3-diaminobutyric polypropylenimine dendrimer to the anti-cancer drug camptothecin with a redox-sensitive disulphide linkage, and evaluate its efficacy to co-deliver the complexed DNA and camptothecin to cancer cells. This PEGylated pro-drug dendrimer was found to spontaneously self-assemble into cationic (∼3–5 mV) vesicles at pH 7.4, at a critical aggregation concentration of about 200 μg mL−1. These vesicles (dendrimersomes) became smaller (150–200 nm) with increasing dendrimer concentration and remained stable over 7 days. They were able to release about 70% of the conjugated camptothecin in presence of 50 mM glutathione (equivalent to the intracellular environment of tumor tissue). They could also condense more than 85% of the DNA at dendrimer : DNA weight ratios of 5 : 1 and higher. DNA condensation occurred instantly and was found to be stable for at least 24 h. This led to an enhanced cellular uptake of DNA (by up to 1.6-fold) and increased gene transfection (by up to 2.4-fold) in prostate cancer cells in comparison with the unmodified dendrimer. These novel dendrimersomes are therefore promising for single carrier-based combination cancer therapy

Redox-sensitive, cholesterol-bearing PEGylated poly(propyleneimine)-based dendrimersomes for drug and gene delivery to cancer cells

Stimuli-responsive nanocarriers have attracted increased attention as materials that can facilitate drug and gene delivery in cancer therapy. The present study reports the development of redox-sensitive dendrimersomes comprising disulfide-linked cholesterol-bearing PEGylated dendrimers, which can be used as drug and gene delivery systems. Two disulfide-linked cholesterol-bearing PEGylated generation 3 diaminobutyric polypropylenimine dendrimers have been successfully synthesized via an in situ two-step reaction. They were able to spontaneously self-assemble into stable, cationic, nanosized vesicles (or dendrimersomes) with lower critical aggregation concentration values for high-cholesterol-bearing vesicles. These dendrimersomes were able to entrap both hydrophilic and hydrophobic dyes, and they also showed a redox-responsive sustained release of the entrapped guests in the presence of a glutathione concentration similar to that of a cytosolic reducing environment. The high-cholesterol-bearing dendrimersomes were found to have a higher melting enthalpy, increased adsorption tendency on mica surface, entrapping ability for a larger amount of hydrophobic drugs, and increased resistance to redox-responsive environments in comparison with their low-cholesterol counterpart. In addition, both dendrimersomes were able to condense more than 85% of the DNA at all the tested ratios for the low-cholesterol vesicles, and at dendrimer : DNA weight ratios of 1 : 1 and higher for the high-cholesterol vesicles. These vesicles resulted in an enhanced cellular uptake of DNA, by up to 15-fold when compared with naked DNA with low-cholesterol vesicles. As a result, they increased the gene transfection on the PC-3 prostate cancer cell line, with the highest transfection being obtained with low-cholesterol vesicle complexes at a dendrimer : DNA weight ratio of 5 : 1 and high-cholesterol vesicle complexes at a dendrimer : DNA weight ratio of 10 : 1. These transfection levels were about 5-fold higher than those observed when treated with naked DNA. These cholesterol-bearing PEGylated dendrimer-based vesicles are, therefore, promising as redox-sensitive drugs and gene delivery systems for potential applications in combination cancer therapies

Increased Myocardial Extracellular Volume in Active Idiopathic Systemic Capillary Leak Syndrome

BACKGROUND: The Systemic Capillary Leak Syndrome (SCLS) is a rare disorder of unknown etiology presenting as recurrent episodes of shock and peripheral edema due to leakage of fluid into soft tissues. Insights into SCLS pathogenesis are few due to the scarcity of cases, and the etiology of vascular barrier disruption in SCLS is unknown. Recent advances in cardiovascular magnetic resonance (CMR) allow for the quantitative assessment of the myocardial extracellular volume (ECV), which can be increased in conditions causing myocardial edema. We hypothesized that measurement of myocardial ECV may detect myocardial vascular leak in patients with SCLS. METHODS: Fifty-six subjects underwent a standard CMR examination at the NIH Clinical Center from 2009 until 2014: 20 patients with acute intermittent SCLS, six subjects with chronic SCLS, and 30 unaffected controls. Standard volumetric measurements; late gadolinium enhancement imaging and pre- and post-contrast T1 mapping were performed. ECV was calculated by calibration of pre- and post-contrast T1 values with blood hematocrit. RESULTS: Demographics and cardiac parameters were similar in both groups. There was no significant valvular disorder in either group. Subjects with chronic SCLS had higher pre-contrast myocardial T1 compared to healthy controls (T1: 1027 ± 44 v. 971 ± 41, respectively; p = 0.03) and higher myocardial ECV than patients with acute intermittent SCLS or controls: 33.8 ± 4.6, 26.9 ± 2.6, 26 ± 2.4, respectively; p = 0.007 v. acute intermittent; P = 0.0005 v. controls). When patients with chronic disease were analyzed together with five patients with acute intermittent disease who had just experienced an acute SCLS flare, ECV values were significantly higher than in subjects with acute intermittent SCLS in remission or age-matched controls and (31.2 ± 4.6 %, 26.5 ± 2.7 %, 26 ± 2.4 %, respectively; p = 0.01 v. remission, p = 0.001 v. controls). By contrast, T1 values did not distinguish these three subgroups (1008 ± 40, 978 ± 40, 971 ± 41, respectively, p = 0.2, active v. remission; p = 0.06 active v. controls). Abundant myocardial edema without evidence of acute inflammation was detected in cardiac tissue postmortem in one patient. CONCLUSIONS: Patients with active SCLS have significantly higher myocardial ECV than age-matched controls or SCLS patients in remission, which correlated with histopathological findings in one patient

Crossing Boundaries: Tapestry Within the Context of the 21st Century

International audienceGraphical model processing is a central problem in artificial intelligence. The optimization of the combined cost of a network of local cost functions federates a variety of famous problems including CSP, SAT and Max-SAT but also optimization in stochastic variants such as Markov Random Fields and Bayesian networks. Exact solving methods for these problems typically include branch and bound and local inference-based bounds.In this paper we are interested in understanding when and how dynamic programming based optimization can be used to efficiently enforce soft local consistencies on Global Cost Functions, defined as parameterized families of cost functions of unbounded arity. Enforcing local consistencies in cost function networks is performed by applying so-called Equivalence Preserving Transformations (EPTs) to the cost functions. These EPTs may transform global cost functions and make them intractable to optimize.We identify as tractable projection-safe those global cost functions whose optimization is and remains tractable after applying the EPTs used for enforcing arc consistency. We also provide new classes of cost functions that are tractable projection-safe thanks to dynamic programming.We show that dynamic programming can either be directly used inside filtering algorithms, defining polynomially DAG-filterable cost functions, or emulated by arc consistency filtering on a Berge-acyclic network of bounded-arity cost functions, defining Berge-acyclic network-decomposable cost functions. We give examples of such cost functions and we provide a systematic way to define decompositions from existing decomposable global constraints.These two approaches to enforcing consistency in global cost functions are then embedded in a solver for extensive experiments that confirm the feasibility and efficiency of our proposal

Influenza Virus in Human Exhaled Breath: An Observational Study

Background: Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection. Methodology/Principal Findings: We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects–three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 µm in diameter. Conclusions: These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission