Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: study protocol for an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) is responsible for about 100,000 maternal deaths every year, most of which occur in low- and middle-income countries. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases blood loss in surgery and reduces death due to bleeding after trauma. When given within 3 h of birth, TXA reduces deaths due to bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. Over one third of pregnant women in the world are anaemic and many are severely anaemic. These women have an increased risk of PPH and suffer more severe outcomes if PPH occurs. There is an urgent need to identify a safe and effective way to reduce postpartum bleeding in anaemic women. METHODS/DESIGN: The WOMAN-2 trial is an international, multicentre, randomised, double-blind, placebo-controlled trial to quantify the effects of TXA on postpartum bleeding in women with moderate or severe anaemia. Ten thousand women with moderate or severe anaemia who have given birth vaginally will be randomised to receive 1 g of TXA or matching placebo by intravenous injection immediately (within 15 min) after the umbilical cord is cut or clamped. The primary outcome is the proportion of women with a clinical diagnosis of primary PPH. The cause of PPH will be described. Data on maternal health and wellbeing, maternal blood loss and its consequences, and other health outcomes will be collected as secondary outcomes. The main analyses will be on an 'intention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses will be based on the severity of anaemia (moderate versus severe) and type of labour (induced or augmented versus spontaneous). A study with 10,000 patients will have over 90% power to detect a 25% relative reduction from 10 to 7.5% in PPH. The trial will be conducted in hospitals in Africa and Asia. DISCUSSION: The WOMAN-2 trial should provide reliable evidence for the effects of TXA for preventing postpartum bleeding in women with anaemia. TRIAL REGISTRATION: ISRCTN, ISRCTN62396133 . Registered on 7 December 2017; ClincalTrials.gov, ID: NCT03475342 . Registered on 23 March 2018

Traffic and Related Self-Driven Many-Particle Systems

Since the subject of traffic dynamics has captured the interest of physicists, many astonishing effects have been revealed and explained. Some of the questions now understood are the following: Why are vehicles sometimes stopped by so-called ``phantom traffic jams'', although they all like to drive fast? What are the mechanisms behind stop-and-go traffic? Why are there several different kinds of congestion, and how are they related? Why do most traffic jams occur considerably before the road capacity is reached? Can a temporary reduction of the traffic volume cause a lasting traffic jam? Under which conditions can speed limits speed up traffic? Why do pedestrians moving in opposite directions normally organize in lanes, while similar systems are ``freezing by heating''? Why do self-organizing systems tend to reach an optimal state? Why do panicking pedestrians produce dangerous deadlocks? All these questions have been answered by applying and extending methods from statistical physics and non-linear dynamics to self-driven many-particle systems. This review article on traffic introduces (i) empirically data, facts, and observations, (ii) the main approaches to pedestrian, highway, and city traffic, (iii) microscopic (particle-based), mesoscopic (gas-kinetic), and macroscopic (fluid-dynamic) models. Attention is also paid to the formulation of a micro-macro link, to aspects of universality, and to other unifying concepts like a general modelling framework for self-driven many-particle systems, including spin systems. Subjects such as the optimization of traffic flows and relations to biological or socio-economic systems such as bacterial colonies, flocks of birds, panics, and stock market dynamics are discussed as well.Comment: A shortened version of this article will appear in Reviews of Modern Physics, an extended one as a book. The 63 figures were omitted because of storage capacity. For related work see http://www.helbing.org

Is there really a beauty premium or an ugliness penalty on earnings?

Purpose Economists have widely documented the “beauty premium” and “ugliness penalty” on earnings. Explanations based on employer and client discrimination would predict a monotonic association between physical attractiveness and earnings; explanations based on occupational self-selection would explain the beauty premium as a function of workers’ occupations; and explanations based on individual differences would predict that the beauty premium would disappear once appropriate individual differences are controlled. In this paper, we empirically tested the three competing hypotheses about the “beauty premium”. Design/Methodology/Approach We analyzed a nationally representative and prospectively longitudinal sample from the National Longitudinal Survey of Adolescent Health (Add Health). Findings Findings The results contradicted the discrimination and self-selection explanations and strongly supported the individual differences explanation. Very unattractive respondents always earned significantly more than unattractive respondents, sometimes more than average-looking or attractive respondents. Multiple regression analyses showed that there was very weak evidence for the beauty premium, and it disappeared completely once individual differences, such as health, intelligence, and Big Five personality factors, were statistically controlled. Implications Past findings of beauty premium and ugliness penalty may possibly be due to the fact that: 1) “very unattractive” and “unattractive” categories are usually collapsed into “below average” category; and 2) health, intelligence (as opposed to education) and Big Five personality factors are not controlled. It appears that more beautiful workers earn more, not because they are beautiful, but because they are healthier, more intelligent, and have better (more Conscientious and Extraverted, and less Neurotic) personality. Originality/Value This is the first study to show that: 1) very unattractive workers have extremely high earnings and earn more than physically more attractive workers, suggesting evidence for the potential ugliness premium; and 2) the apparent beauty premium and ugliness penalty may be a function of unmeasured traits correlated with physical attractiveness, such as health, intelligence, and personality

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

The high energy Universe at ultra-high resolution: the power and promise of X-ray interferometry

We propose the development of X-ray interferometry (XRI), to reveal the Universe at high energies with ultra-high spatial resolution. With baselines which can be accommodated on a single spacecraft, XRI can reach 100 μ as resolution at 10 Å (1.2 keV) and 20 μ as at 2 Å (6 keV), enabling imaging and imaging-spectroscopy of (for example) X-ray coronae of nearby accreting supermassive black holes (SMBH) and the SMBH ‘shadow’; SMBH accretion flows and outflows; X-ray binary winds and orbits; stellar coronae within ∼ 100 pc and many exoplanets which transit across them. For sufficiently luminous sources XRI will resolve sub-pc scales across the entire observable Universe, revealing accreting binary SMBHs and enabling trigonometric measurements of the Hubble constant with X-ray light echoes from quasars or explosive transients. A multi-spacecraft ‘constellation’ interferometer would resolve well below 1 μ as, enabling SMBH event horizons to be resolved in many active galaxies and the detailed study of the effects of strong field gravity on the dynamics and emission from accreting gas close to the black hole

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021