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

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

How Are Completely Desolvated Ions Produced in Electrospray Ionization: Insights from Molecular Dynamics Simulations

We apply molecular dynamics (MD) simulations to study the final phase of electrospray ionization (ESI), where an ion loses all of its associated solvent molecules. By applying an electric field to a cluster of H₂O molecules solvating an ion and including a surrounding gas of varying pressure, we demonstrate that collisions with the gas play a major role in removing this final layer of solvent. We make quantitative predictions of the critical velocity required for the cluster to start losing molecules via collisions with gas and propose that this should be important in real ESI experiments. Such collisions have heretofore not been explicitly considered in discussions of the ESI process

How Are Completely Desolvated Ions Produced in Electrospray Ionization: Insights from Molecular Dynamics Simulations

We apply molecular dynamics (MD) simulations to study the final phase of electrospray ionization (ESI), where an ion loses all of its associated solvent molecules. By applying an electric field to a cluster of H₂O molecules solvating an ion and including a surrounding gas of varying pressure, we demonstrate that collisions with the gas play a major role in removing this final layer of solvent. We make quantitative predictions of the critical velocity required for the cluster to start losing molecules via collisions with gas and propose that this should be important in real ESI experiments. Such collisions have heretofore not been explicitly considered in discussions of the ESI process

Serum Thyrotropin Concentrations are not Predictive of Aggressive Breast Cancer Biology in Euthyroid Individuals

OBJECTIVE: The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin [thyroid-stimulating hormone (TSH)] concentration and markers of aggressive breast cancer biology, as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics. METHODS: This was a retrospective cohort study of patients from 2002–2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and Her2/neu) and pre-diagnosis serum TSH data (n=437) were included. All patients had one of six receptor profiles: ER+ PR+ Her2/neu −, ER+ PR− Her2/neu−, ER+ PR+ Her2/neu+, ER+ PRHer2/ neu+, ER− PR− Her2/neu+, ER− PR− Her2/neu−. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions for a potential relationship with markers of breast cancer aggressiveness. RESULTS: Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu− profile (OR=0.52, p=0.0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, or tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed. CONCLUSIONS: Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort

The emergence of Y-chromosome haplogroup J1e among Arabic-speaking populations

Haplogroup J1 is a prevalent Y-chromosome lineage within the Near East. We report the frequency and YSTR diversity data for its major sub-clade (J1e). The overall expansion time estimated from 453 chromosomes is 10 000 years. Moreover, the previously described J1 (DYS388=13) chromosomes, frequently found in the Caucasus and eastern Anatolian populations, were ancestral to J1e and displayed an expansion time of 9000 years. For J1e, the Zagros/Taurus mountain region displays the highest haplotype diversity, although the J1e frequency increases toward the peripheral Arabian Peninsula. The southerly pattern of decreasing expansion time estimates is consistent with the serial drift and founder effect processes. The first such migration is predicted to have occurred at the onset of the Neolithic, and accordingly J1e parallels the establishment of rain-fed agriculture and semi-nomadic herders throughout the Fertile Crescent. Subsequently, J1e lineages might have been involved in episodes of the expansion of pastoralists into arid habitats coinciding with the spread of Arabic and other Semitic-speaking populations

The ARIEL payload: A technical overview

The Atmospheric Remote-Sensing Infrared Exoplanet Large-survey, ARIEL, has been selected to be the next (M4) medium class space mission in the ESA Cosmic Vision programme. From launch in 2028, and during the following 4 years of operation, ARIEL will perform precise spectroscopy of the atmospheres of ~1000 known transiting exoplanets using its metre-class telescope. A three-band photometer and three spectrometers cover the 0.5 µm to 7.8 µm region of the electromagnetic spectrum. This paper gives an overview of the mission payload, including the telescope assembly, the FGS (Fine Guidance System) - which provides both pointing information to the spacecraft and scientific photometry and low-resolution spectrometer data, the ARIEL InfraRed Spectrometer (AIRS), and other payload infrastructure such as the warm electronics, structures and cryogenic cooling systems