A microgravity isolation mount

The design and preliminary testing of a system for isolating microgravity sensitive payloads from spacecraft vibrational and impulsive disturbances is discussed. The Microgravity Isolation Mount (MGIM) concept consists of a platform which floats almost freely within a limited volume inside the spacecraft, but which is constrained to follow the spacecraft in the long term by means of very weak springs. The springs are realized magnetically and form part of a six degree of freedom active magnetic suspension system. The latter operates without any physical contact between the spacecraft and the platform itself. Power and data transfer is also performed by contactless means. Specifications are given for the expected level of input disturbances and the tolerable level of platform acceleration. The structural configuration of the mount is discussed and the design of the principal elements, i.e., actuators, sensors, control loops and power/data transfer devices are described. Finally, the construction of a hardware model that is being used to verify the predicted performance of the MGIM is described

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

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

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

Nanofabrication of two-dimensional arrays of magnetite particles for fundamental rock magnetic studies

Magnetic measurements of samples with precisely controlled magnetic mineralogy, grain size, and interparticle spacing are needed to provide crucial experimental rock magnetic underpinning for paleomagnetic studies. We report a novel nanofabrication method for producing two-dimensional arrays of cylindrical synthetic magnetite particles with well-defined composition, particle size, and interparticle spacing. The samples are fabricated by writing dot arrays with electron beam lithography, transferring these patterns into sputtered Fe thin films by reactive ion etching in a CO/NH3 plasma, and oxidizing the resulting Fe particles in a controlled atmosphere to form magnetite. Scanning electron microscopy and transmission electron microscopy have been used to monitor the fabrication process and to determine the particle geometry. The particle sizes of our samples range between 100 nm and 265 nm with center-to-center spacings between 180 nm and 310 nm. Low-temperature magnetic remanence data confirm the stoichiometry of the magnetite. We present magnetic hysteresis data and first-order reversal curve diagrams for our samples and compare these with previously published data from other synthetic and natural magnetite samples. The ability to independently control particle size and interparticle spacing of magnetite grains makes our synthetic samples ideal for studying the influence of magnetostatic interactions on the paleomagnetic recording fidelity of naturally occurring magnetite in rocks

Protein synthesis in halophytes: The influence of potassium, sodium and magnesium in vitro

The amino acid (S-35-methionine) incorporating activity of an in vitro wheat germ translation system was found to be maximal in 80 to 125 mol m-3 K with 2 to 4 mol m-3 Mg both as the acetate. Substitution of Na for K, or chloride for acetate at concentrations above 80 mol m-3 inhibited incorporation. When the K acetate concentration was raised to 200 mol m-3, no incorporation of radioactive methionine occurred. Translation by polysomes extracted from leaf tissue of S. maritima, supplemented with post-ribosomal supernatant from wheat germ, showed activity which was optimal in the presence of 225 mol m-3 K acetate and 8 mol m-3 Mg acetate. However, the translation system was not directly comparable with the wheat germ system, as studies with an initiation inhibitor, aurintricarboxylic acid, suggested that the S. maritima system was essentially elongation-dependent, while initiation occurred in the wheat germ system. Elongation-dependent polysomal preparations were extracted from leaves of the glycophytes Pisum sativum, Triticum aestivum, Oryza sativa and Hordeum vulgare, and from the halophytes Atriplex isatidea and Inula crithmoides. Translation by polysomes from the salt-tolerant plants was optimal at higher K and Mg concentrations, than by polysomes from the glycophytes. Furthermore, NaCl was better able partially to substitute for the role of K in polysomal preparations from halophytes than glycophytes