BACKGROUNDNo therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODSWe conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao 2 ) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao 2 ) to the fraction of inspired oxygen (Fio 2 ) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTSA total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS

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The plant circadian clock is proposed to be a network of several interconnected feedback loops, and loss of any component leads to changes in oscillator speed. We previously reported that Arabidopsis thaliana EARLY FLOWERING4 (ELF4) is required to sustain this oscillator and that the elf4 mutant is arrhythmic. This phenotype is shared with both elf3 and lux. Here, we show that overexpression of either ELF3 or LUX ARRHYTHMO (LUX) complements the elf4 mutant phenotype. Furthermore, ELF4 causes ELF3 to form foci in the nucleus. We used expression data to direct a mathematical position of ELF3 in the clock network. This revealed direct effects on the morning clock gene PRR9, and we determined association of ELF3 to a conserved region of the PRR9 promoter. A cis-element in this region was suggestive of ELF3 recruitment by the transcription factor LUX, consistent with both ELF3 and LUX acting genetically downstream of ELF4. Taken together, using integrated approaches, we identified ELF4/ELF3 together with LUX to be pivotal for sustenance of plant circadian rhythms.

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We screened the electronic records of 2,799 patients admitted in Tongji Hospital from January 10th to February 18th, 2020. There were 375 discharged patients including 201 survivors. We built a prognostic prediction model based on XGBoost machine learning algorithm and then tested 29 patients (included 3 patients from other hospital) who were cleared after February 19th. Results:The mean age of the 375 patients was 58.83 years old with 58.7% of males. Fever was the most common initial symptom (49.9%), followed by cough (13.9%), fatigue (3.7%), and dyspnea (2.1%). Our model identified three key clinical features, i.e., lactic dehydrogenase (LDH), lymphocyte and High-sensitivity C-reactive protein (hs-CRP), from a pool of more than 300 features. The clinical route is simple to check and can precisely and quickly assess the risk of death. Therefore, it is of great clinical significance. : medRxiv preprint Conclusion:The three indices-based prognostic prediction model we built is able to predict the mortality risk, and present a clinical route to the recognition of critical cases from severe cases. It can help doctors with early identification and intervention, thus potentially reducing mortality.

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This technical note considers the identification of nonlinear discrete-time systems with additive process noise but without measurement noise. In particular, we propose a method and its associated algorithm to identify the system nonlinear functional forms and their associated parameters from a limited number of time-series data points. For this, we cast this identification problem as a sparse linear regression problem and take a Bayesian viewpoint to solve it. As such, this approach typically leads to nonconvex optimisations. We propose a convexification procedure relying on an efficient iterative reweighted 1-minimisation algorithm that uses general sparsity inducing priors on the parameters of the system and marginal likelihood maximisation. Using this approach, we also show how convex constraints on the parameters can be easily added to the proposed iterative re-weighted 1-minimisation algorithm. In the supplementary material [1], we illustrate the effectiveness of the proposed identification method on two classical systems in biology and physics, namely, a genetic repressilator network and a large scale network of interconnected Kuramoto oscillators.

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