Infants perceive human point-light displays as solid forms

While five-month-old infants show orientation-specific sensitivity to changes in the motion and occlusion patterns of human point-light displays, it is not known whether infants are capable of binding a human representation to these displays. Furthermore, it has been suggested that infants do not encode the same physical properties for humans and material objects. To explore these issues we tested whether infants would selectively apply the principle of solidity to upright human displays. In the first experiment infants aged six and nine months were repeatedly shown a human point-light display walking across a computer screen up to ten times or until habituated. Next, they were repeatedly shown the walking display passing behind an in-depth representation of a table, and finally they were shown the human display appearing to pass through the table top in violation of the solidity of the hidden human form. Both six- and nine-month-old infants showed significantly greater recovery of attention to this final condition. This suggests that infants are able to bind a solid vertical form to human motion. In two further control experiments we presented displays that contained similar patterns of motion but were not perceived by adults as human. Six- and nine-month-old infants did not show recovery of attention when a scrambled display or an inverted human display passed through the table. Thus, the binding of a solid human form to a display in infants only seems to occur for upright human motion. The paper considers the implications of these findings in relation to theories of infants’ developing conceptions of objects, humans and animals

A circle RNA regulatory axis promotes lung squamous metastasis via CDR1-mediated regulation of golgi trafficking

Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of circRNA is through miRNA sponging, we found that miR-671-5pmore potently silenced an axis of CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing of CDR1as or CDR1 significantly inhibited LUSC metastases and CDR1 was sufficient to promote migration and metastases. CDR1, which directly interacted with adaptor protein 1 (AP1) complex subunits and coatomer protein I (COPI) proteins, no longer promoted migration upon blockade of Golgi trafficking. Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced metastasis in vivo. This report demonstrates a novel role for CDR1 in promoting metastasis and Golgi trafficking. These findings reveal an miRNA/ circRNA axis that regulates LUSC metastases through a previously unstudied protein, CDR1. Significance: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1. Significance: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

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

The origin of very wide binary stars

A large population of fragile, wide (> 1000 AU) binary systems exists in the Galactic field and halo. These wide binary stars cannot be primordial because of the high stellar density in star forming regions, while formation by capture in the Galactic field is highly improbable. We propose that these binary systems were formed during the dissolution phase of star clusters (see Kouwenhoven et al. 2010, for details). Stars escaping from a dissolving star cluster can have very similar velocities, which can lead to the formation of a wide binary systems. We carry out N-body simulations to test this hypothesis. The results indicate that this mechanism explains the origin of wide binary systems in the Galaxy. The resulting wide binary fraction and semi-major axis distribution depend on the initial conditions of the dissolving star cluster, while the distributions in eccentricity and mass ratio are universal. Finally, since most stars are formed in (relatively tight) primordial binaries, we predict that a large fraction of the wide "binary stars" are in fact higher-order multiple systems

The formation of very wide binaries

Over the last decades, numerous wide (>1000 AU) binaries have been discovered in the Galactic field and halo. The origin of these wide binaries cannot be explained by star formation or by dynamical interactions in the Galactic field. We explain their existence by wide binary formation during the dissolution phase of young star clusters. In this scenario, two single stars that leave the dissolving cluster at the same time, in the same direction, and with similar velocities, form a new, very wide binary. Using N-body simulations we study how frequently this occurs, and how the orbital parameters of such binaries depend on the properties of the cluster from which they originate. The resulting wide binary fraction for individual star clusters is 1-30%, depending on the initial conditions. As most stars form as part of a binary or multiple system, we predict that a large fraction of these wide binaries are in fact wide triple and quadruple systems

First record of a Jurassic mammal [?'Peramura'] from Ethiopia

The first record of Mesozoic mammals in Ethiopia is a fragment of a lower mammalian molar discovered in residues left after acid dissociation of a small (ca. 4 kg) geological hand sample of a fine−grained bone bed in the lower part of the Mugher Mudstone exposed in the valley of the Jema River. This bone bed is part of a series of estuarine to fluvial deposits that are thought to be of Late Jurassic (Tithonian) age. The fragment preserves the trigonid of a molar; the distal part of its crown is missing. Morphological characters of the trigonid indicate the specimen (JEM−5/21) documents the presence of a mammal with a dentition at either a derived pretribosphenic or primitive tribosphenic grade of evolution. Absence of a well developed basal cingulid around the mesial end of the crown argues against phylogenetic relationships to the australosphenidans. Loss of the distal portion of the crown removed characters critical for determining its grade of evolution. The working hypothesis that JEM−5/21 represents a “peramuran” is advanced for testing. Hypotheses that it represents a mammal with a more derived grade of molar evolution or a previously unknown group of mammals cannot be excluded. JEM−5/21 establishes the presence of mammals in Ethiopia during the Late Jurassic, and its discovery identifies a fossil locality warranting thorough future exploration

The role of maternal anxiety disorder subtype, parenting, and infant stable temperamental inhibition in child anxiety: a prospective longitudinal study

Background:Social Anxiety Disorder (SAD) aggregates in families. To elucidate intergenerational transmission of risk, we examined whether childhood SAD and symptoms of anxiety were prospectively predicted by stable infant temperamental inhibition, maternal SAD, maternal Generalized Anxiety Disorder (GAD), and maternal parenting behaviours.Methods:We conducted a longitudinal study beginning prenatally with follow-up at 4-, 10-, 14- and 58-months postnatally. Mothers were assessed for anxiety disorders prenatally and assigned to one of three groups: SAD (n=67), GAD (n=56), and non-anxious controls (n=94). We assessed infant temperamental inhibition at 4- and 14-months, maternal parenting behaviours at 10- and 58-months, and child anxiety disorders and symptoms at 58-months. Results:Child SAD at 58-months was predicted by prenatal maternal SAD (OR=23.76, 95%CI=1.15-60.37), but not by prenatal maternal GAD (OR = 7.44, 95% CI = 0.32-124.49), stable temperamental inhibition, or maternal behaviours. Child anxiety symptoms at 58-months were predicted specifically by maternal SAD (but not GAD), and also by concurrent maternal intrusiveness. Stable temperamental inhibition moderated the association between 10-month maternal encouragement and 58-month child anxiety symptoms. Conclusions:We found evidence for specificity of risk for child SAD and anxiety symptoms from maternal SAD compared to maternal GAD. Childhood anxiety symptoms were also predicted by an interaction between a lack of maternal encouragement in infancy and stable temperamental inhibition, as well as concurrent maternal intrusiveness. The findings have clinical implications for targeted prevention of child anxiety.<br/