Dynamics of a camphoric acid boat at the air–water interface

We report experiments on an agarose gel tablet loaded with camphoric acid (c-boat) spontaneously set into motion by surface tension gradients on the water surface. We observe three distinct modes of c-boat motion: harmonic mode where the c-boat speed oscillates sinusoidally in time, a steady mode where the c-boat maintains constant speed, and an intermittent mode where the c-boat maintains near-zero speed between sudden jumps in speed. Whereas all three modes have been separately reported before in different systems, controlled release of Camphoric Acid (CA) from the agarose gel matrix allowed the observation of all the three modes in the same system. These three modes are a result of a competition between the driving (surface tension gradients) and drag forces acting on the c-boat. Moreover we suggest that there exist two time scales corresponding to spreading of CA and boat motion and the mismatch of these two time scales give rise to the three modes in boat motion. We reproduced all the modes of motion by varying the air–water interfacial tension using Sodium Dodecyl Sulfate (SDS)

Time-Evolution of a Fractal Distribution: Particle Concentrations in Free-Surface Turbulence

Steady-state turbulence is generated in a tank of water and the trajectories of particles forming a compressible system on the surface are tracked in time. The initial uniformly distributed floating particles coagulate and form a fractal distribution, a rare manifestation of a fractal object observable in real-space. The surface pattern reaches a steady state in approximately 1 s. Measurements are made of the fractal dimensions $D_q(t)$ ($q=1$ to $6$) of the floating particles starting with the uniform distribution $D_q(0)$ = 2 for Taylor Microscale Reynolds number $Re_{\lambda} \simeq 160$. Focus is on the the time-evolution of the correlation dimension $D_2(t)$ as the steady state is approached. This steady state is reached in several large eddy turnover times and does so at an exponential rate

Central nervous system manganese induced lesions and clinical consequences in patients with hereditary hemorrhagic telangiectasia

Abstract Background Around 47–74% of patients with hereditary hemorrhagic telangiectasia (HHT) have hepatic vascular malformations (HVMs); magnetic resonance images (MRI) of the central nervous system (CNS) might show in T1 sequences a hyper-intensity signal in different areas, mainly in the basal ganglia (BG) as consequence of manganese (Mn) deposits as observed in cirrhotic patients. These patients might suffer from different neuropsychiatric disorders (hepatic encephalopathy). In HHT patients, even in the presence of hepatic shunts, hepatocellular function is usually preserved. Additionally, Mn shares iron absorption mechanisms, transferrin and CNS transferrin receptors. In iron deficiency conditions, the Mn may harbor transferrin and access BG. The objectives were to describe frequency of BG Mn deposit-induced lesions (BGMnIL) in HHT patients, its relationship with iron deficiency anemia (IDA) and HVMs. Finally, explore the association between neuropsychological and motor consequences. We performed a cross-sectional study. We determined HHT patients with or without BG-MnIL by the MRI screening of the CNS. We included all patients with lesions and a random sample of those without lesions. All patients underwent standardized and validated neuropsychological assessment to evaluate BG actions. Results were analyzed with multiple logistic regression, adjusting for potential confounders. Results Among 307 participants from a cohort included in the Institutional HHT Registry, 179 patients had MRI performed and Curaçao Criteria ≥3. The prevalence of BG-MnIL was 34.6% (95%CI 27.69-42.09). While neuropsychological symptoms were present in all patients, BG-MnIL patients performed poorly in three of the neuropsychological tests (serial dotting, line tracing time, number connection test A). HVMs frequency in BG-MnIL was 95.1%, versus 71.4% in those without lesions (p < 0.001). IDA frequency was 90.3% versus 54% (p < 0.001). When IDA is present, estimated risk for BG-MnIL is remarkably high (OR 7.73, 95%CI 2.23–26.73). After adjustment for possible confounders (gender, age, presence of HVMs), IDA was still associated with increased risk of BG-MnIL (adjusted OR 6.32, 95% CI 2.32–17.20; p < 0.001). Conclusions Physicians should assess BG-MnIL in HHT patients in CNS-MRI. IDA and HVMs present increased risk of lesions. Patients with BG-MnIL have neuropsychological impairment, and they might benefit from sparing IDA, or undergoing future therapeutic options. Trial registration NCT01761981 . Registered January 3rd 2013

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 &lt;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&lt;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&lt;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