Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial.

BackgroundPlacental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia.MethodsIn this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420.FindingsBetween Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator.InterpretationRepeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended.FundingTommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre

Seasonality and Prevalence of Leishmania major Infection in Phlebotomus duboscqi Neveu-Lemaire from Two Neighboring Villages in Central Mali

Phlebotomus duboscqi is the principle vector of Leishmania major, the causative agent of cutaneous leishmaniasis (CL), in West Africa and is the suspected vector in Mali. Although found throughout the country the seasonality and infection prevalence of P. duboscqi has not been established in Mali. We conducted a three year study in two neighboring villages, Kemena and Sougoula, in Central Mali, an area with a leishmanin skin test positivity of up to 45%. During the first year, we evaluated the overall diversity of sand flies. Of 18,595 flies collected, 12,952 (69%) belonged to 12 species of Sergentomyia and 5,643 (31%) to two species of the genus Phlebotomus, P. duboscqi and P. rodhaini. Of those, P. duboscqi was the most abundant, representing 99% of the collected Phlebotomus species. P. duboscqi was the primary sand fly collected inside dwellings, mostly by resting site collection. The seasonality and infection prevalence of P. duboscqi was monitored over two consecutive years. P. dubsocqi were collected throughout the year. Using a quasi-Poisson model we observed a significant annual (year 1 to year 2), seasonal (monthly) and village effect (Kemena versus Sougoula) on the number of collected P. duboscqi. The significant seasonal effect of the quasi-Poisson model reflects two seasonal collection peaks in May-July and October-November. The infection status of pooled P. duboscqi females was determined by PCR. The infection prevalence of pooled females, estimated using the maximum likelihood estimate of prevalence, was 2.7% in Kemena and Sougoula. Based on the PCR product size, L. major was identified as the only species found in flies from the two villages. This was confirmed by sequence alignment of a subset of PCR products from infected flies to known Leishmania species, incriminating P. duboscqi as the vector of CL in Mali

Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data

Drugs: psychotropic medication

Psychopharmacology offers a range of psychotropic medications to the medical practitioner. The decision to administer such medicines should be made in the context of evidence-based, realistic risk–benefits assessment and sound clinical judgement. With many psychotropics there is a potential for dependence. This can be manifest in two ways; tolerance, where an increased dose is required to produce the same effect, and withdrawal where negative psychological and/or physical consequences are associated with drug discontinuation. Such effects have been characterized in detail from studies of opiate addiction (see ‘Drug dependency: opiates and stimulants’). The following sections summarizes specific health aspects of selected ‘recreational’ and prescription psychotropic agents. Cigarette smoking leads to around 130 000 deaths annually in the UK. Part of the addictive potential of cigarettes lies in the delivery system; inhaled tobacco smoke generates a nicotine ‘hit’ within 10 seconds of inhalation, although nicotine dependence is also evident from other routes such as chewing tobacco. The behavioural effects are due to nicotine binding nicotinic acetylcholine receptors and in regular smokers cholinergic neuroadaptations probably underlie nicotine cravings during abstinence. These are transiently relieved by nicotine administration: indeed there is now strong evidence that while the regular smoker relieves negative effects of nicotine withdrawal they do not gain anything positive (Parrott et al., 2004). Historically it was believed that smoking relieved stress: however there is now strong evidence that nicotine dependence itself causes stress (Parrott, 1999)

Electron acceleration above thunderclouds

The work of MF andAMis sponsored by the Natural Environment Research Council (NERC) under grant NE/H024921/1. IK, OS, RL, and LU are supported by the international cooperation program of the ASCR grant M10042120 and by the GACR project 205-09-1253. JB is supported by the Earth-system project TAMOP-4.2.2.C-11/1/KONV-2012-0015 sponsored by the EU and European Social Foundation. OV is supported by the Spanish Ministry of Science and Innovation under project AYA2011-29936-C05-04. ChH acknowledges an ERC starting grant from the European Union.The acceleration of electrons results in observable electromagnetic waves which can be used for remote sensing. Here, we make use of similar to 4 Hz-66 MHz radio waves emitted by two consecutive intense positive lightning discharges to investigate their impact on the atmosphere above a thundercloud. It is found that the first positive lightning discharge initiates a sprite where electrons are accelerated during the exponential growth and branching of the sprite streamers. This preconditioned plasma above the thundercloud is subsequently exposed to a second positive lightning discharge associated with a bouncing-wave discharge. This discharge process causes a re-brightening of the existing sprite streamers above the thundercloud and initiates a subsequent relativistic electron beam.Publisher PDFPeer reviewe

Whistler Observations on DEMETER Compared with Full Electromagnetic Wave Simulations Sferic Earth Ionosphere (~60 km – 80 km) 0 + Whistler Lightning

International audienceTerrestrial Very Low Frequency (VLF) electromagnetic radiation, which strongly impacts the Van Allen radiation belt electron dynamics, is injected across the ionosphere into the Earth's plasmasphere from two primary sources: man-made VLF transmitters and lightning discharges. Numerical models of trans-ionospheric propagation of such waves remain unvalidated, and early models may have overestimated the absorption, hindering a comprehensive understanding of the global impact of VLF waves in the loss of radiation belt electrons. In an attempt to remedy the problem of a lack of accurate trans-ionospheric propagation models, we have used a full electromagnetic wave method (FWM) numerical code to simulate the propagation of lightning-generated whistlers into the magnetosphere and compared the results with whistlers observed on the DEMETER satellite and paired with lightning stroke data from the National Lightning Detection Network (NLDN). We have identified over 20,000 whistlers occuring in 14 different passes of DEMETER over the central United States during the summer of 2009, and 14,000 of those occured within the 2000 km x 2000 km simulation grid we used. As shown in the attached figure, which shows a histogram of the ratio of the simulated whistler energy to the measured whistler energy for the 14,000 whistlers we compared, the simulation tends to slightly underestimate the total whistler energy injected by about 5 dB. However, the simulation underestimates the DEMETER measurements more as one gets further from the source lightning stroke, so since the signal to noise ratio of more distant whistlers will be smaller, possibly additive noise in the DEMETER measurements (which of course is not accounted for in the model) may explain some of the observed discrepancy