Combined analysis of solar neutrino and solar irradiance data: further evidence for variability of the solar neutrino flux and its implications concerning the solar core

A search for any particular feature in any single solar neutrino dataset is unlikely to establish variability of the solar neutrino flux since the count rates are very low. It helps to combine datasets, and in this article we examine data from both the Homestake and GALLEX experiments. These show evidence of modulation with a frequency of 11.85 yr-1, which could be indicative of rotational modulation originating in the solar core. We find that precisely the same frequency is prominent in power spectrum analyses of the ACRIM irradiance data for both the Homestake and GALLEX time intervals. These results suggest that the solar core is inhomogeneous and rotates with sidereal frequency 12.85 yr-1. We find, by Monte Carlo calculations, that the probability that the neutrino data would by chance match the irradiance data in this way is only 2 parts in 10,000. This rotation rate is significantly lower than that of the inner radiative zone (13.97 yr-1) as recently inferred from analysis of Super-Kamiokande data, suggesting that there may be a second, inner tachocline separating the core from the radiative zone. This opens up the possibility that there may be an inner dynamo that could produce a strong internal magnetic field and a second solar cycle.Comment: 22 pages, 9 tables, 10 figure

Further Evidence Suggestive of a Solar Influence on Nuclear Decay Rates

Recent analyses of nuclear decay data show evidence of variations suggestive of a solar influence. Analyses of datasets acquired at the Brookhaven National Laboratory (BNL) and at the Physikalisch-Technische Bundesanstalt (PTB) both show evidence of an annual periodicity and of periodicities with sidereal frequencies in the neighborhood of 12.25 year^{-1} (at a significance level that we have estimated to be 10^{-17}). It is notable that this implied rotation rate is lower than that attributed to the solar radiative zone, suggestive of a slowly rotating solar core. This leads us to hypothesize that there may be an "inner tachocline" separating the core from the radiative zone, analogous to the "outer tachocline" that separates the radiative zone from the convection zone. The Rieger periodicity (which has a period of about 154 days, corresponding to a frequency of 2.37 year^{-1}) may be attributed to an r-mode oscillation with spherical-harmonic indices l=3, m=1, located in the outer tachocline. This suggests that we may test the hypothesis of a solar influence on nuclear decay rates by searching BNL and PTB data for evidence of a "Rieger-like" r-mode oscillation, with l=3, m=1, in the inner tachocline. The appropriate search band for such an oscillation is estimated to be 2.00-2.28 year^{-1}. We find, in both datasets, strong evidence of a periodicity at 2.11 year^{-1}. We estimate that the probability of obtaining these results by chance is 10^{-12}.Comment: 12 pages, 6 figures, v2 has a color corrected Fig 6, a corrected reference, and a corrected typ

Power Spectrum Analysis of Physikalisch-Technische Bundesanstalt Decay-Rate Data: Evidence for Solar Rotational Modulation

Evidence for an anomalous annual periodicity in certain nuclear decay data has led to speculation concerning a possible solar influence on nuclear processes. We have recently analyzed data concerning the decay rates of Cl-36 and Si-32, acquired at the Brookhaven National Laboratory (BNL), to search for evidence that might be indicative of a process involving solar rotation. Smoothing of the power spectrum by weighted-running-mean analysis leads to a significant peak at frequency 11.18/yr, which is lower than the equatorial synodic rotation rates of the convection and radiative zones. This article concerns measurements of the decay rates of Ra-226 acquired at the Physikalisch-Technische Bundesanstalt (PTB) in Germany. We find that a similar (but not identical) analysis yields a significant peak in the PTB dataset at frequency 11.21/yr, and a peak in the BNL dataset at 11.25/yr. The change in the BNL result is not significant since the uncertainties in the BNL and PTB analyses are estimated to be 0.13/yr and 0.07/yr, respectively. Combining the two running means by forming the joint power statistic leads to a highly significant peak at frequency 11.23/yr. We comment briefly on the possible implications of these results for solar physics and for particle physics.Comment: 15 pages, 13 figure

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Cost-effectiveness of robot-assisted radical cystectomy vs open radical cystectomy for patients with bladder cancer

Importance The value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is unclear. Objectives To compare the cost-effectiveness of iRARC with that of ORC. Design, Setting, and Participants This economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023. Interventions Patients were randomized to receive either iRARC (n = 169) or ORC (n = 169). Main Outcomes and Measures Costs of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion. Results A total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% [95% CI, 0.42%-12.28%]), and readmissions to hospital (14.56% [95% CI, 5.00%-24.11%]), but increases in theater time (31.35 [95% CI, 13.67-49.02] minutes). The additional cost of iRARC per patient was £1124 (95% CI, −£576 to £2824 [US $1622 (95$831 to $4075)]) with an associated gain in quality-adjusted life-years of 0.01124 (95$144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status. Conclusions and Relevance In this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease