Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial

Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD). Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg) or modafinil (200 mg) one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS) by at least 2 grades (responder) and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (P < .0001). Responder rates with armodafinil (72.12%) and modafinil (74.29%) were comparable (P = .76). Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg

Rasch analysis of the Patient and Observer Scar Assessment Scale (POSAS) in burn scars

The Patient and Observer Scar Assessment Scale (POSAS) is a questionnaire that was developed to assess scar quality. It consists of two separate six-item scales (Observer Scale and Patient Scale), both of which are scored on a 10-point rating scale. After many years of experience with this scale in burn scar assessment, it is appropriate to examine its psychometric properties using Rasch analysis. Cross-sectional data collection from seven clinical trials resulted in a data set of 1,629 observer scores and 1,427 patient scores of burn scars. We examined the person-item map, item fit statistics, reliability, response category ordering, and dimensionality of the POSAS. The POSAS showed an adequate fit to the Rasch model, except for the item surface area. Person reliability of the Observer Scale and Patient Scale was 0.82 and 0.77, respectively. Dimensionality analysis revealed that the unexplained variance by the first contrast of both scales was 1.7 units. Spearman correlation between the Observer Scale Rasch measure and the overall opinion of the clinician was 0.75. The Rasch model demonstrated that the POSAS is a reliable and valid scale that measures the single-construct scar qualit

The NANOGrav 15 yr Data Set: Search for Transverse Polarization Modes in the Gravitational-wave Background

\ua9 2024. The Author(s). Published by the American Astronomical Society.Recently we found compelling evidence for a gravitational-wave background with Hellings and Downs (HD) correlations in our 15 yr data set. These correlations describe gravitational waves as predicted by general relativity, which has two transverse polarization modes. However, more general metric theories of gravity can have additional polarization modes, which produce different interpulsar correlations. In this work, we search the NANOGrav 15 yr data set for evidence of a gravitational-wave background with quadrupolar HD and scalar-transverse (ST) correlations. We find that HD correlations are the best fit to the data and no significant evidence in favor of ST correlations. While Bayes factors show strong evidence for a correlated signal, the data does not strongly prefer either correlation signature, with Bayes factors ∼2 when comparing HD to ST correlations, and ∼1 for HD plus ST correlations to HD correlations alone. However, when modeled alongside HD correlations, the amplitude and spectral index posteriors for ST correlations are uninformative, with the HD process accounting for the vast majority of the total signal. Using the optimal statistic, a frequentist technique that focuses on the pulsar-pair cross-correlations, we find median signal-to-noise ratios of 5.0 for HD and 4.6 for ST correlations when fit for separately, and median signal-to-noise ratios of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While the signal-to-noise ratios for each of the correlations are comparable, the estimated amplitude and spectral index for HD are a significantly better fit to the total signal, in agreement with our Bayesian analysis

Comparing Recent Pulsar Timing Array Results on the Nanohertz Stochastic Gravitational-wave Background

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1σ. The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we "extended" each PTA's data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA's Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA

Comparing recent PTA results on the nanohertz stochastic gravitational wave background

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within $1\sigma$. The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we "extended" each PTA's data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings and Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA's Data Release 3, which will involve not just adding in additional pulsars, but also including data from all three PTAs where any given pulsar is timed by more than as single PTA.Comment: 21 pages, 9 figures, submitted to Ap

Long-Term Programming of Antigen-Specific Immunity from Gene Expression Signatures in the PBMC of Rhesus Macaques Immunized with an SIV DNA Vaccine

While HIV-1-specific cellular immunity is thought to be critical for the suppression of viral replication, the correlates of protection have not yet been determined. Rhesus macaques (RM) are an important animal model for the study and development of vaccines against HIV/AIDS. Our laboratory has helped to develop and study DNA-based vaccines in which recent technological advances, including genetic optimization and in vivo electroporation (EP), have helped to dramatically boost their immunogenicity. In this study, RMs were immunized with a DNA vaccine including individual plasmids encoding SIV gag, env, and pol alone, or in combination with a molecular adjuvant, plasmid DNA expressing the chemokine ligand 5 (RANTES), followed by EP. Along with standard immunological assays, flow-based activation analysis without ex vivo restimulation and high-throughput gene expression analysis was performed. Strong cellular immunity was induced by vaccination which was supported by all assays including PBMC microarray analysis that identified the up-regulation of 563 gene sequences including those involved in interferon signaling. Furthermore, 699 gene sequences were differentially regulated in these groups at peak viremia following SIVmac251 challenge. We observed that the RANTES-adjuvanted animals were significantly better at suppressing viral replication during chronic infection and exhibited a distinct pattern of gene expression which included immune cell-trafficking and cell cycle genes. Furthermore, a greater percentage of vaccine-induced central memory CD8+ T-cells capable of an activated phenotype were detected in these animals as measured by activation analysis. Thus, co-immunization with the RANTES molecular adjuvant followed by EP led to the generation of cellular immunity that was transcriptionally distinct and had a greater protective efficacy than its DNA alone counterpart. Furthermore, activation analysis and high-throughput gene expression data may provide better insight into mechanisms of viral control than may be observed using standard immunological assays

How to Detect an Astrophysical Nanohertz Gravitational Wave Background

\ua9 2023. The Author(s). Published by the American Astronomical Society.Analyses of pulsar timing data have provided evidence for a stochastic gravitational wave background in the nanohertz frequency band. The most plausible source of this background is the superposition of signals from millions of supermassive black hole binaries. The standard statistical techniques used to search for this background and assess its significance make several simplifying assumptions, namely (i) Gaussianity, (ii) isotropy, and most often, (iii) a power-law spectrum. However, a stochastic background from a finite collection of binaries does not exactly satisfy any of these assumptions. To understand the effect of these assumptions, we test standard analysis techniques on a large collection of realistic simulated data sets. The data-set length, observing schedule, and noise levels were chosen to emulate the NANOGrav 15 yr data set. Simulated signals from millions of binaries drawn from models based on the Illustris cosmological hydrodynamical simulation were added to the data. We find that the standard statistical methods perform remarkably well on these simulated data sets, even though their fundamental assumptions are not strictly met. They are able to achieve a confident detection of the background. However, even for a fixed set of astrophysical parameters, different realizations of the universe result in a large variance in the significance and recovered parameters of the background. We also find that the presence of loud individual binaries can bias the spectral recovery of the background if we do not account for them