Survival mediation analysis with the death-truncated mediator: The completeness of the survival mediation parameter

In medical research, the development of mediation analysis with a survival outcome has facilitated investigation into causal mechanisms. However, studies have not discussed the death-truncation problem for mediators, the problem being that conventional mediation parameters cannot be well-defined in the presence of a truncated mediator. In the present study, we systematically defined the completeness of causal effects to uncover the gap, in conventional causal definitions, between the survival and nonsurvival settings. We proposed three approaches to redefining the natural direct and indirect effects, which are generalized forms of the conventional causal effects for survival outcomes. Furthermore, we developed three statistical methods for the binary outcome of the survival status and formulated a Cox model for survival time. We performed simulations to demonstrate that the proposed methods are unbiased and robust. We also applied the proposed method to explore the effect of hepatitis C virus infection on mortality, as mediated through hepatitis B viral load

Promoting Behaviour Change in Long term Conditions using a Self-Management Platform

Physical rehabilitation of brain injuries and strokes is a time consuming and costly process. Over the past decade several studies have emerged looking at the use of highly sophisticated technologies, such as robotics and virtual reality to tap into the needs of clinicians and patients. While such technologies can be a valuable tool to facilitate intensive movement practice in a motivating and engaging environment, success of therapy also depends on self-administered therapy beyond hospital stay. With the emergence of low-cost gaming consoles such as the Nintendo Wii, new opportunities arise for home-therapy paradigms centred on social interactions and values, which could reduce the sense of isolation and other depression related complications. In this paper we examine the potential, user acceptance and usability of an unmodified Nintendo Wii gaming console as a low-cost treatment alternative to complement current rehabilitation programmes

High-Pressure Phase Stability and Superconductivity of Pnictogen Hydrides and Chemical Trends for Compressed Hydrides

Binary hydrides formed by the pnictogens of phosphorus, arsenic and antimony are studied at high pressures using first principles methods. Stable structures are predicted and their electronic, vibrational and superconducting properties are investigated. We predict that SbH$_{4}$ and AsH$_{8}$ will be high-temperature superconductors at megabar pressures, with critical temperatures in excess of 100 K. The highly symmetric hexagonal SbH$_{4}$ phase is predicted to be stabilized above about 150 GPa, which is readily achievable in diamond anvil cell experiments. We find that all phosphorus hydrides are metastable with respect to decomposition into the elements within the pressure range studied. Trends based on our results and literature data reveal a connection between the high-pressure behaviors and ambient-pressure chemical quantities which provides insight into understanding which elements may form hydrogen-rich high-temperature superconducting phases at high pressures.The authors thank Eva Zurek for sharing structure data for iodine hydride. The work at Jilin Univ. is supported by the funding of National Natural Science Foundation of China under Grant Nos. 11274136 and 11534003, 2012 Changjiang Scholar of Ministry of Education and the Postdoctoral Science Foundation of China under grant 2013M541283. L.Z. acknowledges funding support from the Recruitment Program of Global Youth Experts in China. Part of calculations was performed in the high performance computing center of Jilin Univ. R.J.N. acknowledges financial support from the Engineering and Physical Sciences Research Council (EPSRC) of the UK [EP/J017639/1]. R.J.N. and C.J.P. acknowledge use of the Archer facility of the U.K.’s national high-performance computing service (for which access was obtained via the UKCP consortium [EP/K013564/1]).This is the final version of the article. It first appeared from ACS via https://doi.org/10.1021/acs.chemmater.5b0463

Mapping the history and current situation of research on John Cunningham virus – a bibliometric analysis

<p>Abstract</p> <p>Background</p> <p>John Cunningham virus (JCV) constitutes a family of polyoma viruses, which plays important roles in the progressive multifocal leukoencephalopathy (PML) and tumorigenesis. However, no bibliometric investigation has been reported to guide the researchers and potential readers.</p> <p>Methods</p> <p>Papers were collected from database Sci-expanded and Pubmed until May 22, 2008. The highly-productive authors, institutes and countries, highly-cited authors and journals were ranked. The highly-cited articles were subjected to co-citation and chronological analysis with highly-frequent MeSH words for co-occurrence analysis.</p> <p>Results</p> <p>Until now, 1785 articles about JCV were indexed in Sci-expanded and 1506 in Pubmed. The main document type was original article. USA, Japan and Italy were the largest three producers about JCV. Temple University published 128 papers and ranked the top, followed by University of Tokyo. Khalili K and Yogo Y became the core authors due to more than 20 documents produced. Journal of Neurovirology published more than 15 papers and ranked the top. Padgett BL and Berger JR were the first two highly-cited authors. Journal of Virology and Journal of Neurovirology respectively ranked to the first two highly-cited journals. These top highly-cited articles were divided into 5 aspects: (1) The correlation between JC virus and tumors; (2) Causal correlation of JCV with PML; (3) Polyoma virus infection and its related diseases in renal-allograft recipients; (4) Detection of JCV antibody, oncogene and its encoding protein; (5) Genetics and molecular biology of JCV. The MeSH/subheadings were classified into five groups: (1) JCV and virus infectious diseases; (2) JCV pathogenicity and pathological appearance of PML; (3) JCV isolation and detection; (4) Immunology of JCV and PML; (5) JCV genetics and tumors.</p> <p>Conclusion</p> <p>JCV investigation mainly focused on its isolation and detection, as well as its correlation with PML and tumors. Establishment of transgenic animal model using JCV T antigen would be a hopeful and useful project in the further study.</p

Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

Why do Particle Clouds Generate Electric Charges?

Grains in desert sandstorms spontaneously generate strong electrical charges; likewise volcanic dust plumes produce spectacular lightning displays. Charged particle clouds also cause devastating explosions in food, drug and coal processing industries. Despite the wide-ranging importance of granular charging in both nature and industry, even the simplest aspects of its causes remain elusive, because it is difficult to understand how inert grains in contact with little more than other inert grains can generate the large charges observed. Here, we present a simple yet predictive explanation for the charging of granular materials in collisional flows. We argue from very basic considerations that charge transfer can be expected in collisions of identical dielectric grains in the presence of an electric field, and we confirm the model's predictions using discrete-element simulations and a tabletop granular experiment

A highly magnified candidate for a young galaxy seen when the Universe was 500 Myrs old

The early Universe at redshift z\sim6-11 marks the reionization of the intergalactic medium, following the formation of the first generation of stars. However, those young galaxies at a cosmic age of \lesssim 500 million years (Myr, at z \gtrsim 10) remain largely unexplored as they are at or beyond the sensitivity limits of current large telescopes. Gravitational lensing by galaxy clusters enables the detection of high-redshift galaxies that are fainter than what otherwise could be found in the deepest images of the sky. We report the discovery of an object found in the multi-band observations of the cluster MACS1149+22 that has a high probability of being a gravitationally magnified object from the early universe. The object is firmly detected (12 sigma) in the two reddest bands of HST/WFC3, and not detected below 1.2 {\mu}m, matching the characteristics of z\sim9 objects. We derive a robust photometric redshift of z = 9.6 \pm 0.2, corresponding to a cosmic age of 490 \pm 15Myr (i.e., 3.6% of the age of the Universe). The large number of bands used to derive the redshift estimate make it one of the most accurate estimates ever obtained for such a distant object. The significant magnification by cluster lensing (a factor of \sim15) allows us to analyze the object's ultra-violet and optical luminosity in its rest-frame, thus enabling us to constrain on its stellar mass, star-formation rate and age. If the galaxy is indeed at such a large redshift, then its age is less than 200 Myr (at the 95% confidence level), implying a formation redshift of zf \lesssim 14. The object is the first z>9 candidate that is bright enough for detailed spectroscopic studies with JWST, demonstrating the unique potential of galaxy cluster fields for finding highly magnified, intrinsically faint galaxies at the highest redshifts.Comment: Submitted to the Nature Journal. 39 Pages, 13 figure

A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road

Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes