Evolution of systemic therapy of advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) commonly occurs in hepatitis B endemic areas, especially in Asian countries. HCC is highly refractory to cytotoxic chemotherapy. This resistance is partly related to its tumor biology, pharmacokinetic properties, and both intrinsic and acquired drug resistance. There is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients. Other systemic approaches, such as hormonal therapy and immunotherapy, have also disappointing results. Recently, encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients. In this review, we concisely summarize the evolution of developments in the systemic therapy of advanced HCC. © 2008 The WJG Press. All rights reserved.published_or_final_versio

Psychiatry and neurodevelopmental disorders: experts by experience, clinical care and research.

People with neurodevelopmental disorders often present with challenging behaviours and psychiatric illnesses. Diagnosis and treatment require patients, families and healthcare professionals to work closely together in partnership, acknowledging their respective areas of expertise. Good treatment outcomes should also be underpinned by robust research evidence. Key research priorities are highlighted

Double-Degenerate Carbon-Oxygen and Oxygen-Neon White Dwarf Mergers: A New Mechanism for Faint and Rapid Type Ia Supernovae

This is the author accepted manuscript. The final version is available from the American Astronomical Society via the DOI in this record.Type Ia supernovae (SNe Ia) originate from the thermonuclear explosion of carbon-oxygen white dwarfs (CO WDs), giving rise to luminous optical transients. A relatively common variety of subluminous SNe Ia events, referred to as SNe Iax, are believed to arise from the failed detonation of a CO WD. In this paper, we explore failed detonation SNe Ia in the context of the double-degenerate channel of merging white dwarfs. In particular, we have carried out the first fully three-dimensional simulation of the merger of a ONe WD with a CO WD. While the hot, tidally-disrupted carbon-rich disk material originating from the CO WD secondary is readily susceptible to detonation in such a merger, the ONe WD primary core is not. This merger yields a failed detonation, resulting in the ejection of a small amount of mass, and leaving behind a kicked, super-Chandrasekhar ONe WD remnant enriched by the fallback of the products of nuclear burning. The resulting outburst is a rapidly-fading optical transient with a small amount of radioactive 56Ni powering the light curve. Consequently, the ONe-CO WD merger naturally produces a very faint and rapidly-fading transient, fainter even than the faintest Type Iax events observed to date, such as SN 2008ha and SN 2010ae. More massive ONe primaries than considered here may produce brighter and longer-duration transients.The work of P.L-A. and E.G.-B. was partially funded by the MINECO AYA2014-59084-P grant and by the AGAUR. RTF thanks the Institute for Theory and Computation at the Harvard-Smithsonian Center for Astrophysics for visiting support during which a portion of this work was undertaken. RTF acknowledges support from NASA 80NSSC18K1013. This work used the Extreme Science and Engineering Discovery Environment (XSEDE) Stampede 2 supercomputer at the University of Texas at Austin’s Texas Advanced Computing Center through allocation TG-AST100038, supported by National Science Foundation grant number ACI-1548562 (Towns et al. 2014)

The Effect of Income on Democracy Revisited a Flexible Distributional Approach

We reexamine the effect of economic development on the level of democracy based on the data sets of Acemoglu et al. (2008) with a novel regression specification utilizing a zero-one-inflated beta distribution for the response variable democracy. The zero-one-inflated beta distribution is more appropriate for continuous but bounded responses with non-zero probabilities for the boundaries of the support than the other frequently used distributions such as the normal. Contrary to the results of Acemoglu et al. (2008), some support of causality is found particularly when explaining the variance of the democracy variables. Since our analysis highlights that the distribution of democracy is bimodal, we approximate the modes using two separate samples of OECD and non-OECD countries. Our results indicate that there are differences not only in the mean but also in other features of the response distribution between the two groups. For instance, higher incomes are associated with higher democracy levels in the OECD sub-sample, however for non-OECD the association is insignificant

Sixteen years of bathymetry and waves at San Diego beaches.

Sustained, quantitative observations of nearshore waves and sand levels are essential for testing beach evolution models, but comprehensive datasets are relatively rare. We document beach profiles and concurrent waves monitored at three southern California beaches during 2001-2016. The beaches include offshore reefs, lagoon mouths, hard substrates, and cobble and sandy (medium-grained) sediments. The data span two energetic El Niño winters and four beach nourishments. Quarterly surveys of 165 total cross-shore transects (all sites) at 100 m alongshore spacing were made from the backbeach to 8 m depth. Monthly surveys of the subaerial beach were obtained at alongshore-oriented transects. The resulting dataset consists of (1) raw sand elevation data, (2) gridded elevations, (3) interpolated elevation maps with error estimates, (4) beach widths, subaerial and total sand volumes, (5) locations of hard substrate and beach nourishments, (6) water levels from a NOAA tide gauge (7) wave conditions from a buoy-driven regional wave model, and (8) time periods and reaches with alongshore uniform bathymetry, suitable for testing 1-dimensional beach profile change models

A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

A network-based dynamical ranking system for competitive sports

From the viewpoint of networks, a ranking system for players or teams in sports is equivalent to a centrality measure for sports networks, whereby a directed link represents the result of a single game. Previously proposed network-based ranking systems are derived from static networks, i.e., aggregation of the results of games over time. However, the score of a player (or team) fluctuates over time. Defeating a renowned player in the peak performance is intuitively more rewarding than defeating the same player in other periods. To account for this factor, we propose a dynamic variant of such a network-based ranking system and apply it to professional men's tennis data. We derive a set of linear online update equations for the score of each player. The proposed ranking system predicts the outcome of the future games with a higher accuracy than the static counterparts.Comment: 6 figure