A Multi-Resolution Weak Lensing Mass Reconstruction Method

Motivated by the limitations encountered with the commonly used direct reconstruction techniques of producing mass maps, we have developed a multi-resolution maximum-likelihood reconstruction method for producing two dimensional mass maps using weak gravitational lensing data. To utilize all the shear information, we employ an iterative inverse method with a properly selected regularization coefficient which fits the deflection potential at the position of each galaxy. By producing mass maps with multiple resolutions in the different parts of the observed field, we can achieve a comparable level of signal to noise by increasing the resolution in regions of higher distortions or regions with an over-density of background galaxies. In addition, we are able to better study the sub-structure of the massive clusters at a resolution which is not attainable in the rest of the observed field. We apply our method to the simulated data and to a four square degree field obtained by the Deep Lens Survey.Comment: Preprint (30 pages, 10 figures), Submitted to Ap

On Statistical Modeling of Sequencing Noise in High Depth Data to Assess Tumor Evolution

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate our model with simulated exponentially expanded populations as well as data from cell line and patient sample dilution experiments, demonstrating its utility in prognosticating tumor progression. Our results may have the potential to identify significant mutations that can cause recurrence. These results are relevant in the pretreatment clinical setting to determine appropriate therapy and prepare for potential recurrence pretreatment

Continuous image distortion by astrophysical thick lenses

Image distortion due to weak gravitational lensing is examined using a non-perturbative method of integrating the geodesic deviation and optical scalar equations along the null geodesics connecting the observer to a distant source. The method we develop continuously changes the shape of the pencil of rays from the source to the observer with no reference to lens planes in astrophysically relevant scenarios. We compare the projected area and the ratio of semi-major to semi-minor axes of the observed elliptical image shape for circular sources from the continuous, thick-lens method with the commonly assumed thin-lens approximation. We find that for truncated singular isothermal sphere and NFW models of realistic galaxy clusters, the commonly used thin-lens approximation is accurate to better than 1 part in 10^4 in predicting the image area and axes ratios. For asymmetric thick lenses consisting of two massive clusters separated along the line of sight in redshift up to \Delta z = 0.2, we find that modeling the image distortion as two clusters in a single lens plane does not produce relative errors in image area or axes ratio more than 0.5%Comment: accepted to GR

Self-reported adverse reactions in 4337 healthcare workers immunizations against novel H1N1 influenza

Purpose: The use of the 2009 H1N1 vaccine has generated much debate concerning safety issues among the general population and physicians. Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccine Methods: We focused on the H1N1 pandemic influenza vaccine Pandemrix(R) and applied a self reporting questionnaire in a population of healthcare workers (HCWs) and medical students at a major university hospital. Results: In total, 4337 individuals were vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination rate of the employees was higher than 40%.The majority of individuals were vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported to lead to one or more adverse reactions (6.7%). Local reactions were reported in 3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%. Conclusions: Our data together with available data from several national and international institutions points to a safe pandemic influenza vaccine

Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4

Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota, and TLR4 activation in non-bone marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease

Age Distribution of Cases of 2009 (H1N1) Pandemic Influenza in Comparison with Seasonal Influenza

INTRODUCTION: Several aspects of the epidemiology of 2009 (H1N1) pandemic influenza have not been accurately determined. We sought to study whether the age distribution of cases differs in comparison with seasonal influenza. METHODS: We searched for official, publicly available data through the internet from different countries worldwide on the age distribution of cases of influenza during the 2009 (H1N1) pandemic influenza period and most recent seasonal influenza periods. Data had to be recorded through the same surveillance system for both compared periods. RESULTS: For 2009 pandemic influenza versus recent influenza seasons, in USA, visits for influenza-like illness to sentinel providers were more likely to involve the age groups of 5-24, 25-64 and 0-4 years compared with the reference group of >64 years [odds ratio (OR) (95% confidence interval (CI)): 2.43 (2.39-2.47), 1.66 (1.64-1.69), and 1.51 (1.48-1.54), respectively]. Pediatric deaths were less likely in the age groups of 2-4 and <2 years than the reference group of 5-17 years [OR (95% CI): 0.46 (0.25-0.85) and 0.49 (0.30-0.81), respectively]. In Australia, notifications for laboratory-confirmed influenza were more likely in the age groups of 10-19, 5-9, 20-44, 45-64 and 0-4 years than the reference group of >65 years [OR (95% CI): 7.19 (6.67-7.75), 5.33 (4.90-5.79), 5.04 (4.70-5.41), 3.12 (2.89-3.36) and 1.89 (1.75-2.05), respectively]. In New Zealand, consultations for influenza-like illness by sentinel providers were more likely in the age groups of <1, 1-4, 35-49, 5-19, 20-34 and 50-64 years than the reference group of >65 years [OR (95% CI): 2.38 (1.74-3.26), 1.99 (1.62-2.45), 1.57 (1.30-1.89), 1.57 (1.30-1.88), 1.40 (1.17-1.69) and 1.39 (1.14-1.70), respectively]. CONCLUSIONS: The greatest increase in influenza cases during 2009 (H1N1) pandemic influenza period, in comparison with most recent seasonal influenza periods, was seen for school-aged children, adolescents, and younger adults

Genomic Signature-Based Identification of Influenza A Viruses Using RT-PCR/Electro-Spray Ionization Mass Spectrometry (ESI-MS) Technology

BACKGROUND: The emergence and rapid spread of the 2009 H1N1 pandemic influenza A virus (H1N1pdm) in humans highlights the importance of enhancing the capability of existing influenza surveillance systems with tools for rapid identification of emerging and re-emerging viruses. One of the new approaches is the RT-PCR electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology, which is based on analysis of base composition (BC) of RT-PCR amplicons from influenza "core" genes. Combination of the BC signatures represents a "genomic print" of an influenza A virus. METHODOLOGY/PRINCIPAL FINDINGS: Here, 757 samples collected between 2006 and 2009 were tested, including 302 seasonal H1N1, 171 H3N2, 7 swine triple reassortants, and 277 H1N1pdm viruses. Of the 277 H1N1pdm samples, 209 were clinical specimens (throat, nasal and nasopharyngeal swabs, nasal washes, blood and sputum). BC signatures for the clinical specimen from one of the first cases of the 2009 pandemic, A/California/04/2009, confirmed it as an unusual, previously unrecognized influenza A virus, with "core" genes related to viruses of avian, human and swine origins. Subsequent analysis of additional 276 H1N1pdm samples revealed that they shared the genomic print of A/California/04/2009, which differed from those of North American swine triple reassortant viruses, seasonal H1N1 and H3N2 and other viruses tested. Moreover, this assay allowed distinction between "core" genes of co-circulating groups of seasonal H1N1, such as clades 2B, 2C, and their reassortants with dual antiviral resistance to adamantanes and oseltamivir. CONCLUSIONS/SIGNIFICANCE: The RT-PCR/ESI-MS assay is a broad range influenza identification tool that can be used directly on clinical specimens for rapid and accurate detection of influenza virus genes. The assay differentiates the H1N1pdm from seasonal and other nonhuman hosts viruses. Although not a diagnostic tool, this assay demonstrates its usefulness and robustness in influenza virus surveillance and detection of novel and unusual viruses with previously unseen genomic prints

Global circulation patterns of seasonal influenza viruses vary with antigenic drift.

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.T.B. was supported by a Newton International Fellowship from the Royal Society and through NIH U54 GM111274. S.R. was supported by MRC (UK, Project MR/J008761/1), Wellcome Trust (UK, Project 093488/Z/10/Z), Fogarty International Centre (USA, R01 TW008246‐01), DHS (USA, RAPIDD program), NIGMS (USA, MIDAS U01 GM110721‐01) and NIHR (UK, Health Protection Research Unit funding). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza was supported by the Australian Government Department of Health and thanks N. Komadina and Y.‐M. Deng. The Atlanta WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza was supported by the U.S. Department of 13 Health and Human Services. NIV thanks A.C. Mishra, M. Chawla‐Sarkar, A.M. Abraham, D. Biswas, S. Shrikhande, AnuKumar B, and A. Jain. Influenza surveillance in India was expanded, in part, through US Cooperative Agreements (5U50C1024407 and U51IP000333) and by the Indian Council of Medical Research. M.A.S. was supported through NSF DMS 1264153 and NIH R01 AI 107034. Work of the WHO Collaborating Centre for Reference and Research on Influenza at the MRC National Institute for Medical Research was supported by U117512723. P.L., A.R. & M.A.S were supported by EU Seventh Framework Programme [FP7/2007‐2013] under Grant Agreement no. 278433-­‐PREDEMICS and ERC Grant agreement no. 260864. C.A.R. was supported by a University Research Fellowship from the Royal Society.This is the author accepted manuscript. It is currently under infinite embargo pending publication of the final version

De novo transcriptome reconstruction and annotation of the Egyptian rousette bat

Background The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. Results Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. Conclusion We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission