Phase transitions in self-dual generalizations of the Baxter-Wu model

We study two types of generalized Baxter-Wu models, by means of transfer-matrix and Monte Carlo techniques. The first generalization allows for different couplings in the up- and down triangles, and the second generalization is to a $q$-state spin model with three-spin interactions. Both generalizations lead to self-dual models, so that the probable locations of the phase transitions follow. Our numerical analysis confirms that phase transitions occur at the self-dual points. For both generalizations of the Baxter-Wu model, the phase transitions appear to be discontinuous.Comment: 29 pages, 13 figure

Soil nutrients and beta diversity in the Bornean Dipterocarpaceae: evidence for niche partitioning by tropical rain forest trees

1   The relative importance of niche- and dispersal-mediated processes in structuring diverse tropical plant communities remains poorly understood. Here, we link mesoscale beta diversity to soil variation throughout a lowland Bornean watershed underlain by alluvium, sedimentary and granite parent materials ( c . 340 ha, 8–200 m a.s.l.). We test the hypothesis that species turnover across the habitat gradient reflects interspecific partitioning of soil resources. 2   Floristic inventories (≥ 1 cm d.b.h.) of the Dipterocarpaceae, the dominant Bornean canopy tree family, were combined with extensive soil analyses in 30 (0.16 ha) plots. Six samples per plot were analysed for total C, N, P, K, Ca and Mg, exchangeable K, Ca and Mg, extractable P, texture, and pH. 3   Extractable P, exchangeable K, and total C, N and P varied significantly among substrates and were highest on alluvium. Thirty-one dipterocarp species ( n  = 2634 individuals, five genera) were recorded. Dipterocarp density was similar across substrates, but richness and diversity were highest on nutrient-poor granite and lowest on nutrient-rich alluvium. 4   Eighteen of 22 species were positively or negatively associated with parent material. In 8 of 16 abundant species, tree distribution (≥ 10 cm d.b.h.) was more strongly non-random than juveniles (1–10 cm d.b.h.), suggesting higher juvenile mortality in unsuitable habitats. The dominant species Dipterocarpus sublamellatus (> 50% of stems) was indifferent to substrate, but nine of 11 ‘subdominant’ species (> 8 individuals ha −1 ) were substrate specialists. 5   Eighteen of 22 species were significantly associated with soil nutrients, especially P, Mg and Ca. Floristic variation was significantly correlated with edaphic and geographical distance for all stems ≥ 1 cm d.b.h. in Mantel analyses. However, juvenile variation (1–10 cm d.b.h.) was more strongly related to geographical distance than edaphic factors, while the converse held for established trees (≥ 10 cm d.b.h.), suggesting increased importance of niche processes with size class. 6   Pervasive dipterocarp associations with soil factors suggest that niche partitioning structures dipterocarp tree communities. Yet, much floristic variation unrelated to soil was correlated with geographical distance between plots, suggesting that dispersal and niche processes jointly determine mesoscale beta diversity in the Bornean Dipterocarpaceae. Journal of Ecology (2005) doi: 10.1111/j.1365-2745.2005.01077.xPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72822/1/j.1365-2745.2005.01077.x.pd

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

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