Precision Prediction for the Big-Bang Abundance of Primordial Helium

Within the standard models of particle physics and cosmology we have calculated the big-bang prediction for the primordial abundance of \he to a theoretical uncertainty of less than 0.1 \pct $(\delta Y_P < \pm 0.0002)$, improving the current theoretical precision by a factor of 10. At this accuracy the uncertainty in the abundance is dominated by the experimental uncertainty in the neutron mean lifetime, $\tau_n = 885.4 \pm 2.0 sec$. The following physical effects were included in the calculation: the zero and finite-temperature radiative, Coulomb and finite-nucleon-mass corrections to the weak rates; order-$\alpha$ quantum-electrodynamic correction to the plasma density, electron mass, and neutrino temperature; and incomplete neutrino decoupling. New results for the finite-temperature radiative correction and the QED plasma correction were used. In addition, we wrote a new and independent nucleosynthesis code designed to control numerical errors to be less than 0.1\pct. Our predictions for the \EL[4]{He} abundance are presented in the form of an accurate fitting formula. Summarizing our work in one number, $Y_P(\eta = 5\times 10^{-10}) = 0.2462 \pm 0.0004 (expt) \pm < 0.0002 (theory)$. Further, the baryon density inferred from the Burles-Tytler determination of the primordial D abundance, $\Omega_B h^2 = 0.019\pm 0.001$, leads to the prediction: $Y_P = 0.2464 \pm 0.0005 (D/H) \pm < 0.0002 (theory) \pm 0.0005 (expt)$. This ``prediction'' and an accurate measurement of the primeval \he abundance will allow an important consistency test of primordial nucleosynthesis.Comment: Replaced fitting formulas - new versions differ by small but significant amount. Other minor changes. 30 pages, 17 figures, 5 table

Turning Around the Sphaleron Bound: Electroweak Baryogenesis in an Alternative Post-inflationary Cosmology

The usual sphaleron bound and the statement of the impossibility of baryon production at a second order phase transition or analytic cross-over are reformulated in the first part of the paper as requirements of the expansion rate of the Universe at the electroweak scale. With an (exact or effective) additional contribution to the energy density scaling as 1/a^6, which dominates until just before nucleosynthesis, the observed baryon asymmetry may be produced at the electroweak scale in simple extensions of the Minimal Standard Model, even in the case that the phase transition is not first order. We focus our attention on one such cosmology, in which the Universe goes through a period termed `kination' in which its energy is dominated by the kinetic energy of a scalar field. The required kinetic energy dominated modes can occur either as a field rolls down an exponential (or steeper) potential, or in the oscillation of a field about the minimum of a steep power-law potential. We implement in detail the former case with a single exponential field first driving inflation, and then rolling into a kinetic energy dominated mode. Reheating is achieved using an alternative to the usual mechanism due to Spokoiny, in which the Universe is `reheated' by particle creation in the expanding background. Density perturbations of the magnitude required for structure formation may also be generated. We show that the analogous model for the power-law potential cannot be consistently implemented. In models with inflation driven by a second field and the usual mechanism of reheating (by decay of the inflaton) the required kinetic energy dominated cosmology is viable in both types of potential.Comment: 44 pages, ReVTeX, with 9 postscipt figures (included); minor modifications to figure

Relaxing the Big-bang Bound to the Baryon Density

In the standard picture of big-bang nucleosynthesis the yields of D, $^3$He, $^4$He, and $^7$Li only agree with their inferred primordial abundances if the fraction of critical density contributed by baryons is between $0.01h^{-2}$ and $0.02h^{-2}$ ($h$ is the present value of the Hubble constant in units of 100\kms\Mpc^{-1}). This is the basis of the very convincing and important argument that baryons can contribute at most 10\% of critical density and thus cannot close the Universe. Nonstandard scenarios involving decaying particles,$^1$ inhomogeneities in the baryon density,$^2$ and even more exotic ideas$^3$ put forth to evade this bound have been largely unsuccessful.$^4$ We suggest a new way of relaxing the bound: If the tau neutrino has a mass of 20\MeV-30\MeV and lifetime of $200\sec -1000\sec$, and its decay products include electron neutrinos, the bound to the baryon mass density can be loosened by a about factor of $10$. The key is the decay-generated electron antineutrinos: around the time of nucleosynthesis they are captured by protons to produce neutrons, thereby changing the outcome of nucleosynthesis. Experiments at $e^\pm$ colliders should soon be sensitive to a tau-neutrino mass in the required range.Comment: 10p, FERMILAB Pub-94/059A, Figs available on reques

Big-bang Nucleosynthesis Enters the Precision Era

The last parameter of big-bang nucleosynthesis, the baryon density, is being pinned down by measurements of the deuterium abundance in high-redshift hydrogen clouds. When it is determined, it will fix the primeval light-element abundances. D, ^3He and ^7Li will become ``tracers'' for the study of Galactic and stellar chemical evolution, and big-bang nucleosynthesis will become an even sharper probe of particle physics, e.g., the bound to the number of light neutrino species will be tightened significantly. Two key tests of the consistency of the standard theory are on the horizon: an independent, high-precision determination of the baryon density from anisotropy of the cosmic background radiation and a precision determination of the primeval $^4$He abundance.Comment: 19 pages Latex; 8 eps figures; submitted to Rev Mod Phys (Colloquia

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?

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Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570