Changes in Inflammatory and Atherogenesis Biomarkers With the 2-Drug Regimen Dolutegravir Plus Lamivudine in Antiretroviral Therapy-Experienced, Virologically Suppressed People With HIV-1: A Systematic Literature Review

Background: The 2-drug regimen dolutegravir plus lamivudine has demonstrated long-term noninferior efficacy vs 3-/4-drug regimens (3/4DRs) in phase 3 trials. This systematic literature review summarizes clinical trial and real-world evidence evaluating impact of dolutegravir plus lamivudine on inflammatory and atherogenesis biomarkers in people with human immunodeficiency virus type 1 (PWH). Methods: Using Ovid MEDLINE, Embase, PubMed, and Cochrane library databases and conference proceedings, we searched for studies published from 1 January 2013 to 14 July 2021, reporting changes in inflammatory and atherogenesis biomarkers with dolutegravir plus lamivudine in antiretroviral therapy-experienced, virologically suppressed PWH aged 6518 years. Results: Four records representing 2 randomized controlled trials (RCTs) and 6 records of real-world evidence met eligibility criteria. All real-world studies evaluated CD4+/CD8+\u2005ratio, while only 1 assessed inflammatory biomarkers. Across both RCTs, no consistent pattern of change in biomarkers was observed between dolutegravir/lamivudine and 3/4DR comparators. There were significant changes in soluble CD14 favoring dolutegravir/lamivudine in TANGO at weeks 48 and 144 and SALSA at week 48, and in interleukin-6 favoring the control group in TANGO at weeks 48 and 144. In the real-world study evaluating inflammatory biomarkers, median soluble CD14 significantly decreased 48 weeks postswitch to dolutegravir plus lamivudine (P\u2005<\u2005.001), while other biomarkers remained stable. In all 6 real-world studies, increases in CD4+/CD8+\u2005ratio were reported after switch to dolutegravir plus lamivudine (follow-up, 12-60 months). Conclusions: Results show that dolutegravir plus lamivudine has a comparable impact on inflammatory and atherogenesis biomarkers vs 3/4DRs, with no consistent pattern of change after switch in virologically suppressed PWH

Between Pixels And Play: The Role of the Photograph in Videogame Nostalgias

The histories of videogames are so often contained with nostalgia for the screen, for the arcade, console, computer or game box design, and for the experience of playing itself. Various amateur photographs now archived on Flickr allow us to remember beyond the stereotypical, albeit iconic, imagery of Pac-Man and Space Invaders. The essence of play becomes captured in the photograph as a “collective memory” and “reflective nostalgia” for the places, times and actions inherent in the histories of the early 1970s and 1980s videogame era. It is through debating the so-often implied “reconstructed nostalgias” offered by videogame companies to consumers in their remakes of classic game titles that this paper explores “reflective nostalgia” of videogames by examining the role of photographs taken during the act of playing these games. In doing so it reframes 1980s videogame nostalgias beyond the “mediated space” of the screen, and moves instead towards the “play space” as another way of keeping these histories alive

The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

Background The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. Results Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. Conclusions These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

The ethical and moral responsibility of producing queer YA literature

This research project is an extension of a project I entered previously for my Banned Books course in Spring 2013. This project proved to be bigger than the confines of the assignment. I originally researched Rainbow Boys in Banned Books of America. I researched why it was banned or challenged and why its representation of queer teenagers mattered to those who read the book. However, in this new project I want to take it a step further. I want to focus on why equal representations of queer youth and queer youth of color in fictional Young Adult (and adult) matters. I will research what representation is currently available and also offer a brief history of queer YA literature and how far it has come since then. In my project I will also address the lack of positive representation and how it affects people who identify as queer and how it also plays a role when it intersects with their ethnicity/race. After doing this, I will want to find a way for the media to correct such failures and offer alternatives. I will also research currently available resources for finding good representation for queer people. Hopefully by the end of this research project, I will be able to educate those about matters of intersectionality and representation and why it matters in literature and will be able to show how it will benefit our society and most importantly how offering more resources and representation in novels will help those who live in a cisgender, white and heteronormative America. (Author abstract)Donovan, T. (2014). The ethical and moral responsibility of producing queer young adult literature. Retrieved from http://academicarchive.snhu.ed