Ultra Long Period Cepheids: a primary standard candle out to the Hubble flow

The cosmological distance ladder crucially depends on classical Cepheids (with P=3-80 days), which are primary distance indicators up to 33 Mpc. Within this volume, very few SNe Ia have been calibrated through classical Cepheids, with uncertainty related to the non-linearity and the metallicity dependence of their period-luminosity (PL) relation. Although a general consensus on these effects is still not achieved, classical Cepheids remain the most used primary distance indicators. A possible extension of these standard candles to further distances would be important. In this context, a very promising new tool is represented by the ultra-long period (ULP) Cepheids (P \geq 80 days), recently identified in star-forming galaxies. Only a small number of ULP Cepheids have been discovered so far. Here we present and analyse the properties of an updated sample of 37 ULP Cepheids observed in galaxies within a very large metallicity range of 12+log(O/H) from ~7.2 to 9.2 dex. We find that their location in the colour(V-I)-magnitude diagram as well as their Wesenheit (V-I) index-period (WP) relation suggests that they are the counterparts at high luminosity of the shorter-period (P \leq 80 days) classical Cepheids. However, a complete pulsation and evolutionary theoretical scenario is needed to properly interpret the true nature of these objects. We do not confirm the flattening in the studied WP relation suggested by Bird et al. (2009). Using the whole sample, we find that ULP Cepheids lie around a relation similar to that of the LMC, although with a large spread (~0.4 mag).Comment: 8 pages, 4 figures, accepted for publication in Astrophysics & Space Scienc

Vortex states in 2D superconductor at high magnetic field in a periodic pinning potential

The effect of a periodic pinning array on the vortex state in a 2D superconductor at low temperatures is studied within the framework of the Ginzburg-Landau approach. It is shown that attractive interaction of vortex cores to a commensurate pin lattice stabilizes vortex solid phases with long range positional order against violent shear fluctuations. Exploiting a simple analytical method, based on the Landau orbitals description, we derive a rather detailed picture of the low temperatures vortex state phase diagram. It is predicted that for sufficiently clean samples application of an artificial periodic pinning array would enable one to directly detect the intrinsic shear stiffness anisotropy characterizing the ideal vortex lattice.Comment: 8 pages, 5 figure

Observing Supermassive Black Holes across cosmic time: from phenomenology to physics

In the last decade, a combination of high sensitivity, high spatial resolution observations and of coordinated multi-wavelength surveys has revolutionized our view of extra-galactic black hole (BH) astrophysics. We now know that supermassive black holes reside in the nuclei of almost every galaxy, grow over cosmological times by accreting matter, interact and merge with each other, and in the process liberate enormous amounts of energy that influence dramatically the evolution of the surrounding gas and stars, providing a powerful self-regulatory mechanism for galaxy formation. The different energetic phenomena associated to growing black holes and Active Galactic Nuclei (AGN), their cosmological evolution and the observational techniques used to unveil them, are the subject of this chapter. In particular, I will focus my attention on the connection between the theory of high-energy astrophysical processes giving rise to the observed emission in AGN, the observable imprints they leave at different wavelengths, and the methods used to uncover them in a statistically robust way. I will show how such a combined effort of theorists and observers have led us to unveil most of the SMBH growth over a large fraction of the age of the Universe, but that nagging uncertainties remain, preventing us from fully understating the exact role of black holes in the complex process of galaxy and large-scale structure formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and Treves A. (Eds), 2015, Springer International Publishing AG, Cha

Formation and Evolution of Supermassive Black Holes

The correlation between the mass of supermassive black holes in galaxy nuclei and the mass of the galaxy spheroids or bulges (or more precisely their central velocity dispersion), suggests a common formation scenario for galaxies and their central black holes. The growth of bulges and black holes can commonly proceed through external gas accretion or hierarchical mergers, and are both related to starbursts. Internal dynamical processes control and regulate the rate of mass accretion. Self-regulation and feedback are the key of the correlation. It is possible that the growth of one component, either BH or bulge, takes over, breaking the correlation, as in Narrow Line Seyfert 1 objects. The formation of supermassive black holes can begin early in the universe, from the collapse of Population III, and then through gas accretion. The active black holes can then play a significant role in the re-ionization of the universe. The nuclear activity is now frequently invoked as a feedback to star formation in galaxies, and even more spectacularly in cooling flows. The growth of SMBH is certainly there self-regulated. SMBHs perturb their local environment, and the mergers of binary SMBHs help to heat and destroy central stellar cusps. The interpretation of the X-ray background yields important constraints on the history of AGN activity and obscuration, and the census of AGN at low and at high redshifts reveals the downsizing effect, already observed for star formation. History appears quite different for bright QSO and low-luminosity AGN: the first grow rapidly at high z, and their number density decreases then sharply, while the density of low-luminosity objects peaks more recently, and then decreases smoothly.Comment: 31 pages, 13 figures, review paper for Astrophysics Update

Five-Year Mortality for Adults Entering Human Immunodeficiency Virus Care Under Universal Early Treatment Compared With the General US Population

Background: Mortality among adults with human immunodeficiency virus (HIV) remains elevated over those in the US general population, even in the years after entry into HIV care. We explore whether the elevation in 5-year mortality would have persisted if all adults with HIV had initiated antiretroviral therapy within 3 months of entering care. Methods: Among 82 766 adults entering HIV care at North American AIDS Cohort Collaboration clinical sites in the United States, we computed mortality over 5 years since entry into HIV care under observed treatment patterns. We then used inverse probability weights to estimate mortality under universal early treatment. To compare mortality with those for similar individuals in the general population, we used National Center for Health Statistics data to construct a cohort representing the subset of the US population matched to study participants on key characteristics. Results: For the entire study period (1999-2017), the 5-year mortality among adults with HIV was 7.9% (95% confidence interval [CI]: 7.6%-8.2%) higher than expected based on the US general population. Under universal early treatment, the elevation in mortality for people with HIV would have been 7.2% (95% CI: 5.8%-8.6%). In the most recent calendar period examined (2011-2017), the elevation in mortality for people with HIV was 2.6% (95% CI: 2.0%-3.3%) under observed treatment patterns and 2.1% (.0%-4.2%) under universal early treatment. Conclusions: Expanding early treatment may modestly reduce, but not eliminate, the elevation in mortality for people with HIV

Effect of Adopting the New Race-Free 2021 Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate Creatinine Equation on Racial Differences in Kidney Disease Progression among People with Human Immunodeficiency Virus: An Observational Study

Background: The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. Methods: We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. Results: With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI],. 73-.82), an equal risk of progressing from stage 2 to 3 (1.00;. 92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. Conclusions: The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD

Virologic outcomes among adults with HIV using integrase inhibitor-based antiretroviral therapy

Background: Integrase strand transfer inhibitor (InSTI)-based regimens have been recommended as first-line antiretroviral therapy (ART) for adults with HIV. But data on long-term effects of InSTI-based regimens on virologic outcomes remain limited. Here we examined whether InSTI improved long-term virologic outcomes compared with efavirenz (EFV). Methods: We included adults from the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen containing either InSTI or EFV between 2009 and 2016. We estimated differences in the proportion virologically suppressed up to 7 years of follow-up in observational intention-to-treat and per-protocol analyses. Results: Of 15 318 participants, 5519 (36%) initiated an InSTI-based regimen and 9799 (64%) initiated the EFV-based regimen. In observational intention-to-treat analysis, 81.3% of patients in the InSTI group and 67.3% in the EFV group experienced virologic suppression at 3 months after ART initiation, corresponding to a difference of 14.0% (95% CI 12.4 – 15.6). At 1 year after ART initiation, the proportion virologically suppressed was 89.5% in the InSTI group and 90.2% in the EFV group, corresponding to a difference of -0.7% (95% CI -2.1 to 0.8). At 7 years, the proportion virologically suppressed was 94.5% in the InSTI group and 92.5% in the EFV group, corresponding to a difference of 2.0% (95% CI -7.3 to 11.3). The observational per-protocol results were similar to intention-to-treat analyses. Conclusions: Although InSTI-based initial ART regimens had more rapid virologic response than EFV-based regimens, the long-term virologic effect was similar. Our findings may inform guidelines regarding preferred initial regimens for HIV treatment

Clinical Effectiveness of Integrase Strand Transfer Inhibitor–Based Antiretroviral Regimens Among Adults With Human Immunodeficiency Virus: A Collaboration of Cohort Studies in the United States and Canada

Background. Integrase strand transfer inhibitor (InSTI)–based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes. Methods. We included participants from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen, containing either InSTI (ie, raltegravir, dolutegravir, and elvitegravir-cobicistat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RDs), and hazard ratios (HRs) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal disease, end-stage liver disease, or death. Results. Of 15 993 participants, 5824 (36%) initiated an InSTI-based and 10 169 (64%) initiated an EFV-based regimen. During the 6-year follow-up, 440 in the InSTI group and 1097 in the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% and 14.3% for the InSTI and EFV groups, respectively, corresponding to a RD of 0.3% (95% confidence interval, −2.7% to 3.3%) and a HR of 1.08 (.97–1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding to a RD of 0.3% (−3.0% to 3.7%) and a HR of 1.09 (.96–1.25). Conclusions. InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART

Association of Race and Ethnicity with Initial Prescription of Antiretroviral Therapy among People with HIV in the US

Importance: Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) is currently the guideline-recommended first-line treatment for HIV. Delayed prescription of INSTI-containing ART may amplify differences and inequities in health outcomes. Objectives: To estimate racial and ethnic differences in the prescription of INSTI-containing ART among adults newly entering HIV care in the US and to examine variation in these differences over time in relation to changes in treatment guidelines. Design, Setting, and Participants: Retrospective observational study of 42841 adults entering HIV care from October 12, 2007, when the first INSTI was approved by the US Food and Drug Administration, to April 30, 2019, at more than 200 clinical sites contributing to the North American AIDS Cohort Collaboration on Research and Design. Exposures: Combined race and ethnicity as reported in patient medical records. Main Outcomes and Measures: Probability of initial prescription of ART within 1 month of care entry and probability of being prescribed INSTI-containing ART. Differences among non-Hispanic Black and Hispanic patients compared with non-Hispanic White patients were estimated by calendar year and time period in relation to changes in national guidelines on the timing of treatment initiation and recommended initial treatment regimens. Results: Of 41263 patients with information on race and ethnicity, 19378 (47%) as non-Hispanic Black, 6798 (16%) identified as Hispanic, and 13539 (33%) as non-Hispanic White; 36394 patients (85%) were male, and the median age was 42 years (IQR, 30 to 51). From 2007-2015, when guidelines recommended treatment initiation based on CD4+ cell count, the probability of ART initiation within 1 month of care entry was 45% among White patients, 45% among Black patients (difference, 0% [95% CI, -1% to 1%]), and 51% among Hispanic patients (difference, 5% [95% CI, 4% to 7%]). From 2016-2019, when guidelines strongly recommended treating all patients regardless of CD4+ cell count, this probability increased to 66% among White patients, 68% among Black patients (difference, 2% [95% CI, -1% to 5%]), and 71% among Hispanic patients (difference, 5% [95% CI, 1% to 9%]). INSTIs were prescribed to 22% of White patients and only 17% of Black patients (difference, -5% [95% CI, -7% to -4%]) and 17% of Hispanic patients (difference, -5% [95% CI, -7% to -3%]) from 2009-2014, when INSTIs were approved as initial therapy but were not yet guideline recommended. Significant differences persisted for Black patients (difference, -6% [95% CI, -8% to -4%]) but not for Hispanic patients (difference, -1% [95% CI, -4% to 2%]) compared with White patients from 2014-2017, when INSTI-containing ART was a guideline-recommended option for initial therapy; differences by race and ethnicity were not statistically significant from 2017-2019, when INSTI-containing ART was the single recommended initial therapy for most people with HIV. Conclusions and Relevance: Among adults entering HIV care within a large US research consortium from 2007-2019, the 1-month probability of ART prescription was not significantly different across most races and ethnicities, although Black and Hispanic patients were significantly less likely than White patients to receive INSTI-containing ART in earlier time periods but not after INSTIs became guideline-recommended initial therapy for most people with HIV. Additional research is needed to understand the underlying racial and ethnic differences and whether the differences in prescribing were associated with clinical outcomes.