Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

Gross-Neveu Models, Nonlinear Dirac Equations, Surfaces and Strings

Recent studies of the thermodynamic phase diagrams of the Gross-Neveu model (GN2), and its chiral cousin, the NJL2 model, have shown that there are phases with inhomogeneous crystalline condensates. These (static) condensates can be found analytically because the relevant Hartree-Fock and gap equations can be reduced to the nonlinear Schr\"odinger equation, whose deformations are governed by the mKdV and AKNS integrable hierarchies, respectively. Recently, Thies et al have shown that time-dependent Hartree-Fock solutions describing baryon scattering in the massless GN2 model satisfy the Sinh-Gordon equation, and can be mapped directly to classical string solutions in AdS3. Here we propose a geometric perspective for this result, based on the generalized Weierstrass spinor representation for the embedding of 2d surfaces into 3d spaces, which explains why these well-known integrable systems underlie these various Gross-Neveu gap equations, and why there should be a connection to classical string theory solutions. This geometric viewpoint may be useful for higher dimensional models, where the relevant integrable hierarchies include the Davey-Stewartson and Novikov-Veselov systems.Comment: 27 pages, 1 figur

A surprising consistency between the far-infrared galaxy luminosity functions of the field and Coma

We present new deep images of the Coma Cluster from the ESA Herschel Space Observatory at wavelengths of 70, 100 and 160 μm, covering an area of 1.75 × 1.0 square degrees encompassing the core and south-west infall region. Our data display an excess of sources at flux densities above 100 mJy compared to blank-field surveys, as expected. We use extensive optical spectroscopy of this region to identify cluster members and hence produce cluster luminosity functions in all three photometric bands. We compare our results to the local field galaxy luminosity function, and the luminosity functions from the Herschel Virgo Cluster Survey. We find consistency between the shapes of the Coma and field galaxy luminosity functions at all three wavelengths; however, we do not find the same level of agreement with that of the Virgo Cluster

Quantification of ocean heat uptake from changes in atmospheric O2 and CO2 composition

The ocean is the main source of thermal inertia in the climate system. Ocean heat uptake during recent decades has been quantified using ocean temperature measurements. However, these estimates all use the same imperfect ocean dataset and share additional uncertainty due to sparse coverage, especially before 2007. Here, we provide an independent estimate by using measurements of atmospheric oxygen (O2) and carbon dioxide (CO2) – levels of which increase as the ocean warms and releases gases – as a whole ocean thermometer. We show that the ocean gained 1.29 ± 0.79 × 1022 Joules of heat per year between 1991 and 2016, equivalent to a planetary energy imbalance of 0.80 ± 0.49 W watts per square metre of Earth’s surface. We also find that the ocean-warming effect that led to the outgassing of O2 and CO2 can be isolated from the direct effects of anthropogenic emissions and CO2 sinks. Our result – which relies on high-precision O2 atmospheric measurements dating back to 1991 – leverages an integrative Earth system approach and provides much needed independent confirmation of heat uptake estimated from ocean data

Hierarchy measure for complex networks

Nature, technology and society are full of complexity arising from the intricate web of the interactions among the units of the related systems (e.g., proteins, computers, people). Consequently, one of the most successful recent approaches to capturing the fundamental features of the structure and dynamics of complex systems has been the investigation of the networks associated with the above units (nodes) together with their relations (edges). Most complex systems have an inherently hierarchical organization and, correspondingly, the networks behind them also exhibit hierarchical features. Indeed, several papers have been devoted to describing this essential aspect of networks, however, without resulting in a widely accepted, converging concept concerning the quantitative characterization of the level of their hierarchy. Here we develop an approach and propose a quantity (measure) which is simple enough to be widely applicable, reveals a number of universal features of the organization of real-world networks and, as we demonstrate, is capable of capturing the essential features of the structure and the degree of hierarchy in a complex network. The measure we introduce is based on a generalization of the m-reach centrality, which we first extend to directed/partially directed graphs. Then, we define the global reaching centrality (GRC), which is the difference between the maximum and the average value of the generalized reach centralities over the network. We investigate the behavior of the GRC considering both a synthetic model with an adjustable level of hierarchy and real networks. Results for real networks show that our hierarchy measure is related to the controllability of the given system. We also propose a visualization procedure for large complex networks that can be used to obtain an overall qualitative picture about the nature of their hierarchical structure.Comment: 29 pages, 9 figures, 4 table

Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification

Stromal-derived intratumoural heterogeneity (ITH) has been shown to undermine molecular stratification of patients into appropriate prognostic/predictive subgroups. Here, using several clinically relevant colorectal cancer (CRC) gene expression signatures, we assessed the susceptibility of these signatures to the confounding effects of ITH using gene expression microarray data obtained from multiple tumour regions of a cohort of 24 patients, including central tumour, the tumour invasive front and lymph node metastasis. Sample clustering alongside correlative assessment revealed variation in the ability of each signature to cluster samples according to patient-of-origin rather than region-of-origin within the multi-region dataset. Signatures focused on cancer-cell intrinsic gene expression were found to produce more clinically useful, patient-centred classifiers, as exemplified by the CRC intrinsic signature (CRIS), which robustly clustered samples by patient-of-origin rather than region-of-origin. These findings highlight the potential of cancer-cell intrinsic signatures to reliably stratify CRC patients by minimising the confounding effects of stromal-derived ITH

Evaluation of whole genome sequencing for outbreak detection of Salmonella enterica

Salmonella enterica is a common cause of minor and large food borne outbreaks. To achieve successful and nearly 'real-time' monitoring and identification of outbreaks, reliable sub-typing is essential. Whole genome sequencing (WGS) shows great promises for using as a routine epidemiological typing tool. Here we evaluate WGS for typing of S. Typhimurium including different approaches for analyzing and comparing the data. A collection of 34 S. Typhimurium isolates was sequenced. This consisted of 18 isolates from six outbreaks and 16 epidemiologically unrelated background strains. In addition, 8 S. Enteritidis and 5 S. Derby were also sequenced and used for comparison. A number of different bioinformatics approaches were applied on the data; including pan-genome tree, k-mer tree, nucleotide difference tree and SNP tree. The outcome of each approach was evaluated in relation to the association of the isolates to specific outbreaks. The pan-genome tree clustered 65% of the S. Typhimurium isolates according to the pre-defined epidemiology, the k-mer tree 88%, the nucleotide difference tree 100% and the SNP tree 100% of the strains within S. Typhimurium. The resulting outcome of the four phylogenetic analyses were also compared to PFGE revealing that WGS typing achieved the greater performance than the traditional method. In conclusion, for S. Typhimurium, SNP analysis and nucleotide difference approach of WGS data seem to be the superior methods for epidemiological typing compared to other phylogenetic analytic approaches that may be used on WGS. These approaches were also superior to the more classical typing method, PFGE. Our study also indicates that WGS alone is insufficient to determine whether strains are related or un-related to outbreaks. This still requires the combination of epidemiological data and whole genome sequencing results

Estimating the Impact of Plasma HIV-1 RNA Reductions on Heterosexual HIV-1 Transmission Risk

Background: The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions. Methodology/Principal Findings: We use prospective data collected from 2004 to 2008 in East and Southern African HIV-1 serodiscordant couples to model the relationship of plasma HIV-1 RNA levels and heterosexual transmission risk with confirmation of HIV-1 transmission events by HIV-1 sequencing. The model is based on follow-up of 3381 HIV-1 serodiscordant couples over 5017 person-years encompassing 108 genetically-linked HIV-1 transmission events. HIV-1 transmission risk was 2.27 per 100 person-years with a log-linear relationship to log10 plasma HIV-1 RNA. The model predicts that a decrease in average plasma HIV-1 RNA of 0.74 log10 copies/mL (95% CI 0.60 to 0.97) reduces heterosexual transmission risk by 50%, regardless of the average starting plasma HIV-1 level in the population and independent of other HIV-1-related population characteristics. In a simulated population with a similar plasma HIV-1 RNA distribution the model estimates that 90% of overall HIV-1 infections averted by a 0.74 copies/mL reduction in plasma HIV-1 RNA could be achieved by targeting this reduction to the 58% of the cohort with plasma HIV-1 levels ≥4 log10 copies/mL. Conclusions/Significance: This log-linear model of plasma HIV-1 levels and risk of sexual HIV-1 transmission may help estimate the impact on HIV-1 transmission and infections averted from candidate interventions that reduce plasma HIV-1 RNA levels

IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni

Dental amalgam and mercury in dentistry

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Mercury in dentistry has re-emerged as a contentious issue in public health, predominantly because so many people are inadvertently exposed to mercury in order to obtain the benefits of dental amalgam fillings, and the risks remain difficult to interpret. This commentary aims to examine the issues involved in public policy assessment of the continued use of dental amalgam in dentistry.AJ Spence