Clinical Reactivations of Herpes Simplex Virus Type 2 Infection and Human Immunodeficiency Virus Disease Progression Markers

BACKGROUND: The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear. METHODS: Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS) into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit. RESULTS: A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p = 0.004), an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001) and 51 to 101 reduced CD4+ T cells/mm(3) over time compared to asymptomatic HSV-2 infection (trend p<0.001). CONCLUSIONS: HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C

Since HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to Minimal Hepatic Encephalopathy (MHE) in the absence of cirrhosis

Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-sectional and longitudinal clinical data

Abstract Objective To evaluate the utility of a single quantitative PCR (qPCR) measurement of HSV (HSV-1&amp;2) DNA in cervicovaginal lavage (CVL) specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH) within a cohort with semiannual schedule of follow up and collection of specimens. Methods Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data. Results The PCR assay was sensitive and reproducible with a limit of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences. Conclusion Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients

Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease

People living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes up-regulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD

Searches for Neutrinos from Gamma-Ray Bursts Using the IceCube Neutrino Observatory

Gamma-ray bursts (GRBs) are considered as promising sources of ultra-high-energy cosmic rays (UHECRs) due to their large power output. Observing a neutrino flux from GRBs would offer evidence that GRBs are hadronic accelerators of UHECRs. Previous IceCube analyses, which primarily focused on neutrinos arriving in temporal coincidence with the prompt gamma-rays, found no significant neutrino excess. The four analyses presented in this paper extend the region of interest to 14 days before and after the prompt phase, including generic extended time windows and targeted precursor searches. GRBs were selected between 2011 May and 2018 October to align with the data set of candidate muon-neutrino events observed by IceCube. No evidence of correlation between neutrino events and GRBs was found in these analyses. Limits are set to constrain the contribution of the cosmic GRB population to the diffuse astrophysical neutrino flux observed by IceCube. Prompt neutrino emission from GRBs is limited to ≲1% of the observed diffuse neutrino flux, and emission on timescales up to 104 s is constrained to 24% of the total diffuse flux.Peer Reviewe

Neutrino interferometry for high-precision tests of Lorentz symmetry with IceCube

We acknowledge the support from the following agencies: USA—US National Science Foundation–Office of Polar Programs, US National Science Foundation–Physics Division, Wisconsin Alumni Research Foundation, Center for High Throughput Computing (CHTC) at the University of Wisconsin–Madison, Open Science Grid (OSG), Extreme Science and Engineering Discovery Environment (XSEDE), US Department of Energy–National Energy Research Scientific Computing Center, Particle astrophysics research computing centre at the University of Maryland, Institute for Cyber-Enabled Research at Michigan State University and Astroparticle physics computational facility at Marquette University; Belgium—Funds for Scientific Research (FRS-FNRS and FWO), FWO Odysseus and Big Science programmes, and Belgian Federal Science Policy Office (Belspo); Germany—Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Helmholtz Alliance for Astroparticle Physics (HAP), Initiative and Networking Fund of the Helmholtz Association, Deutsches Elektronen Synchrotron (DESY), and High Performance Computing cluster of the RWTH Aachen; Sweden—Swedish Research Council, Swedish Polar Research Secretariat, Swedish National Infrastructure for Computing (SNIC), and Knut and Alice Wallenberg Foundation; Australia—Australian Research Council; Canada—Natural Sciences and Engineering Research Council of Canada, Calcul Québec, Compute Ontario, Canada Foundation for Innovation, WestGrid and Compute Canada; Denmark—Villum Fonden, Danish National Research Foundation (DNRF); New Zealand—Marsden Fund; Japan—Japan Society for Promotion of Science (JSPS) and Institute for Global Prominent Research (IGPR) of Chiba University; Korea—National Research Foundation of Korea (NRF); Switzerland—Swiss National Science Foundation (SNSF); UK—Science and Technology Facilities Council (STFC) and The Royal Society

A muon-track reconstruction exploiting stochastic losses for large-scale Cherenkov detectors

IceCube is a cubic-kilometer Cherenkov telescope operating at the South Pole. The main goal of IceCube is the detection of astrophysical neutrinos and the identification of their sources. High-energy muon neutrinos are observed via the secondary muons produced in charge current interactions with nuclei in the ice. Currently, the best performing muon track directional reconstruction is based on a maximum likelihood method using the arrival time distribution of Cherenkov photons registered by the experiment's photomultipliers. A known systematic shortcoming of the prevailing method is to assume a continuous energy loss along the muon track. However at energies $>1$ TeV the light yield from muons is dominated by stochastic showers. This paper discusses a generalized ansatz where the expected arrival time distribution is parametrized by a stochastic muon energy loss pattern. This more realistic parametrization of the loss profile leads to an improvement of the muon angular resolution of up to $20\%$ for through-going tracks and up to a factor 2 for starting tracks over existing algorithms. Additionally, the procedure to estimate the directional reconstruction uncertainty has been improved to be more robust against numerical errors

Observation of high-energy neutrinos from the Galactic plane

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, has been a mystery for over a century. Due to deflection in interstellar magnetic fields, cosmic rays from the Milky Way arrive at Earth from random directions. However, near their sources and during propagation, cosmic rays interact with matter and produce high-energy neutrinos. We search for neutrino emission using machine learning techniques applied to ten years of data from the IceCube Neutrino Observatory. We identify neutrino emission from the Galactic plane at the 4.5$\sigma$ level of significance, by comparing diffuse emission models to a background-only hypothesis. The signal is consistent with modeled diffuse emission from the Galactic plane, but could also arise from a population of unresolved point sources.Comment: Submitted on May 12th, 2022; Accepted on May 4th, 202

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale νμ_{μ} Disappearance at IceCube

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter εμτ. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of −0.0041≤εμτ≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date