Extragalactic Peaked-Spectrum Radio Sources at Low Frequencies

This document is the Accepted Manuscript of the following article: J.R. Callingham, et al, 'Extragalactic Peaked-Spectrum Radio Sources at Low Frequencies', The Astrophysical Journal, 836 (2), (28pp), first published online 17 February 2017. DOI: https://doi.org/10.3847/1538-4357-836/2/174. © 2017, The American Astronomical Society. All rights reserved. Data tables, and the appendix containing all of the SEDs, are available from the journal and on request to the authorWe present a sample of 1,483 sources that display spectral peaks between 72 MHz and 1.4 GHz, selected from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. The GLEAM survey is the widest fractional bandwidth all-sky survey to date, ideal for identifying peaked-spectrum sources at low radio frequencies. Our peaked-spectrum sources are the low frequency analogues of gigahertz-peaked spectrum (GPS) and compact-steep spectrum (CSS) sources, which have been hypothesized to be the precursors to massive radio galaxies. Our sample more than doubles the number of known peaked-spectrum candidates, and 95% of our sample have a newly characterized spectral peak. We highlight that some GPS sources peaking above 5 GHz have had multiple epochs of nuclear activity, and demonstrate the possibility of identifying high redshift ($z > 2$) galaxies via steep optically thin spectral indices and low observed peak frequencies. The distribution of the optically thick spectral indices of our sample is consistent with past GPS/CSS samples but with a large dispersion, suggesting that the spectral peak is a product of an inhomogeneous environment that is individualistic. We find no dependence of observed peak frequency with redshift, consistent with the peaked-spectrum sample comprising both local CSS sources and high-redshift GPS sources. The 5 GHz luminosity distribution lacks the brightest GPS and CSS sources of previous samples, implying that a convolution of source evolution and redshift influences the type of peaked-spectrum sources identified below 1 GHz. Finally, we discuss sources with optically thick spectral indices that exceed the synchrotron self-absorption limit.Peer reviewedFinal Accepted Versio

SARS-CoV-2 antibody kinetics in blood donors with a previously positive SARS-CoV-2 antibody test within a seroprevalence survey

The persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is a matter of importance regarding the coronavirus disease 19 (COVID-19) pandemic. To observe antibody dynamics, 105 blood donors, positive for SARS-CoV-2 antibodies by a lateral flow test within a seroprevalence study, were included in this study. Thirty-nine (37%) of 105 the donors were confirmed positive by a total Ig Wantai enzyme-linked immunosorbent assay (ELISA). Three (8%) in this group of 39 reported severe and 26/39 (67%) mild to moderate COVID-19 symptoms. By further ELISA-testing, 33/39 (85%) donors were initially positive for IgG antibodies, 31/39 (79%) for IgA, and 32/39 (82%) for IgM, while 27/39 (69%) were positive for all three isotypes. Persistence of IgG, IgA, and IgM was observed in 73%, 79%, and 32% of donors, respectively, after 6–9 months of observation. For IgM antibodies, the decline in the proportion of positive donors was statistically significant (p = 0.002) during 12 months observation, for IgG only the decline at 3 months was statistically significant (p = 0.042). Four donors exhibited notable increases in antibody levels. In conclusion, persistent SARS-CoV-2 IgA antibodies and IgG antibodies at 6–9 months are present in approximately three of four individuals with previous mild to moderate COVID-19.</p

Pneumocystis Pneumonia—Is it Still a Threat Among People With Human Immunodeficiency Virus (HIV)?:A Danish HIV Cohort Study

Background We aimed to examine pneumocystis pneumonia (PCP) risk and mortality among people with human immunodeficiency virus (HIV), and associations with (1) time after HIV diagnosis, (2) calendar time, and (3) CD4 cell count. Methods From the Danish HIV cohort study, we identified all adult people with HIV (PWH) (1995-2021). We estimated incidence rates (IRs) and mortality rates. We used Poisson regression analysis to compute adjusted incidence ratios (IRRs) and mortality rate ratios. PCP risk was assessed according to time after HIV diagnosis, calendar time, and low CD4 cell count. Results Among 4882 PWH (53 647 person-years), we observed 336 PCP events (for the time period 2016-2021 compared to 1995-1999, PCP risk decreased by &gt;90% after the first year of HIV diagnosis; aIRR, 0.08 [95% confidence interval {CI},. 02-.29], and by &gt;40% in the first year, if baseline CD4 count was &lt;200 cells/μL [aIRR, 0.57 [95% CI,. 36-.90]). However, no statistically significant change in PCP risk was observed after 1995-1999 for the latter group. PCP risk remained high if the CD4 count was 100 to &lt;200 cells/μL (IR, 16.08 [95% CI, 5.19-49.89]) during the first year of combination antiretroviral therapy (cART), despite a suppressed viral load. Major reductions were found after 1 year of cART (CD4 count 100 to &lt;200 cells/μL). Although nonsignificant, the 3- and 12-month mortality rate decreased by 80% from 1995-1999 to 2016-2021. Conclusions PCP remains a significant problem among late presenters with HIV, emphasizing the importance of early HIV diagnosis. Continuing PCP prophylaxis until the CD4 count is &gt;100 cells/μL, with at least 1 year of cART and viral suppression for &gt;3 months should be considered; however; further studies are needed to confirm these results.</p

Missed Opportunities to Diagnose Common Variable Immunodeficiency:a Population-Based Case–Control Study Identifying Indicator Diseases for Common Variable Immunodeficiency

Purpose: Delayed diagnosis of common variable immunodeficiency (CVID) remains a serious problem. We investigated whether some diseases diagnosed during out-patient visits or admission to hospitals could act as indicator conditions for CVID diagnosis. Methods: In this nested case–control study, we identified 128 cases diagnosed with CVID in Denmark (1999–2013) and 640 age-, gender-, and region-matched controls. We obtained data on diseases diagnosed at hospitals in the five years before CVID diagnosis from The National Hospital Registry. We grouped hospital diagnoses in 33 major disease categories and 210 subcategories. We used conditional logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (CI) to estimate associations between disease exposure and subsequent CVID. Results: During the five years preceding a CVID diagnosis, cases had four times as many hospital contacts as the controls (p &lt; 0.001). A diagnosis in 18 major disease categories showed a significant OR for subsequent diagnosis of CVID. The most substantial association with a subsequent CVID diagnosis was a diagnosis of lower respiratory tract infections (OR: 29.9; 95% CI: 14.2–63.2) and lung diseases (35.1; 15.0–82.5). We observed a similar association when we removed the last year before diagnosis from analysis and overall, in the years &lt; 1, ≥ 1–3, and ≥ 3–5 before diagnosis, although the absolute number of exposures was small. Twenty-eight specific diseases displayed an at least 3-fold risk of subsequent CVID diagnosis. Conclusion: Targeted screening for antibody deficiency in patients diagnosed with specific diseases associated with CVID may lead to earlier CVID diagnosis and treatment and thereby potentially reduced morbidity and mortality.</p

Socioenvironmental Adversity and Adolescent Psychotic Experiences: Exploring Potential Mechanisms in a UK Longitudinal Cohort

Background and hypothesisChildren exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not been previously investigated. We hypothesized that cognitive ability and inflammation would partly explain this association.Study designData were utilized from the Environmental-Risk Longitudinal Twin Study, a cohort of 2232 children born in 1994-1995 in England and Wales and followed to age 18. Socioenvironmental adversities were measured from birth to age 10 and classified into physical risk (defined by high urbanicity and air pollution) and socioeconomic risk (defined by high neighborhood deprivation, neighborhood disorder, and family disadvantage). Cognitive abilities (overall, crystallized, fluid, and working memory) were assessed at age 12; and inflammatory markers (C-reactive protein, interleukin-6, soluble urokinase plasminogen activator receptor) were measured at age 18 from blood samples. Participants were interviewed at age 18 regarding psychotic experiences.Study resultsHigher physical risk and socioeconomic risk were associated with increased odds of psychotic experiences in adolescence. The largest mediation pathways were from socioeconomic risk via overall cognitive ability and crystallized ability, which accounted for ~11% and ~19% of the association with psychotic experiences, respectively. No statistically significant pathways were found via inflammatory markers in exploratory (partially cross-sectional) analyses.ConclusionsCognitive ability, especially crystallized ability, may partly explain the association between childhood socioenvironmental adversity and adolescent psychotic experiences. Interventions to support cognitive development among children living in disadvantaged settings could buffer them against developing subclinical psychotic phenomena

Outcome of SARS-CoV-2 infection among patients with common variable immunodeficiency and a matched control group: A Danish nationwide cohort study.

The risk of severe adult respiratory coronavirus-2 (SARS-CoV-2) infection and the course of the infection among individuals with common variable immunodeficiency (CVID) relative to the general population have been a matter of debate. We conducted a Danish nationwide study comparing the timing of SARS-CoV-2 vaccination, the risk of first confirmed SARS-CoV-2 infection, re-infection, and the outcome of infection among individuals with CVID relative to an age- and gender matched control group. Cox regression was used to calculate incidence rate ratios. The CVID patients received SARS-CoV-2 vaccinations earlier than those included in the population control group. Even so, the risks of both first infection and re-infection were increased among the individuals with CVID. The CVID group also had increased risk for hospital contacts due to SARS-CoV-2 infection relative to the general population. However, reassuringly, the risk of mechanical ventilation and death did not differ between the groups, but the numbers were low in both groups, making the estimates uncertain. Though this is the largest study to investigate the risk of SARS-CoV-2 infections and outcomes hereof among individuals with CVID relative to the general population, we cannot rule out minor differences in severity, which might only be detectable with an even larger sample size

Comparison of vaccine-induced antibody neutralization against SARS-CoV-2 variants of concern following primary and booster doses of COVID-19 vaccines

The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad protection against current and emerging SARS-CoV-2 variants

Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756

Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence:the randomized phase 2a TITAN trial

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 .</p