Recent studies suggest that most cases of myelodysplastic syndrome (MDS) are clonally heterogeneous, with a founding clone and multiple subclones. It is not known whether specific gene mutations ...typically occur in founding clones or subclones. We screened a panel of 94 candidate genes in a cohort of 157 patients with MDS or secondary acute myeloid leukemia (sAML). This included 150 cases with samples obtained at MDS diagnosis and 15 cases with samples obtained at sAML transformation (8 were also analyzed at the MDS stage). We performed whole-genome sequencing (WGS) to define the clonal architecture in eight sAML genomes and identified the range of variant allele frequencies (VAFs) for founding clone mutations. At least one mutation or cytogenetic abnormality was detected in 83% of the 150 MDS patients and 17 genes were significantly mutated (false discovery rate ≤0.05). Individual genes and patient samples displayed a wide range of VAFs for recurrently mutated genes, indicating that no single gene is exclusively mutated in the founding clone. The VAFs of recurrently mutated genes did not fully recapitulate the clonal architecture defined by WGS, suggesting that comprehensive sequencing may be required to accurately assess the clonal status of recurrently mutated genes in MDS.
The LUX-ZEPLIN (LZ) experiment Akimov, D.Yu; Angelides, N.; Araújo, H.M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2020, Volume:
953, Issue:
C
Journal Article
Peer reviewed
Open access
We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time ...projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850’ level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements.
Recent studies show widespread encroachment of forest into savannas with important consequences for the global carbon cycle and land-atmosphere interactions. However, little research has focused on ...in situ measurements of the successional sequence of savanna to forest in Africa. Using long-term inventory plots we quantify changes in vegetation structure, above-ground biomass (AGB) and biodiversity of trees ≥10 cm diameter over 20 years for five vegetation types: savanna; colonising forest (F1), monodominant Okoume forest (F2); young Marantaceae forest (F3); and mixed Marantaceae forest (F4) in Lopé National Park, central Gabon, plus novel 3D terrestrial laser scanning (TLS) measurements to assess forest structure differences. Over 20 years no plot changed to a new stage in the putative succession, but F1 forests strongly moved towards the structure, AGB and diversity of F2 forests. Overall, savanna plots showed no detectable change in structure, AGB or diversity using this method, with zero trees ≥10 cm diameter in 1993 and 2013. F1 and F2 forests increased in AGB, mainly as a result of adding recruited stems (F1) and increased Basal Area (F2), whereas F3 and F4 forests did not change substantially in structure, AGB or diversity. Critically, the stability of the F3 stage implies that this stage may be maintained for long periods. Soil carbon was low, and did not show a successional gradient as for AGB and diversity. TLS vertical plant profiles showed distinctive differences amongst the vegetation types, indicating that this technique can improve ecological understanding. We highlight two points: (i) as forest colonises, changes in biodiversity are much slower than changes in forest structure or AGB; and (ii) all forest types store substantial quantities of carbon. Multi-decadal monitoring is likely to be required to assess the speed of transition between vegetation types.
The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is ...smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.
Summary Background Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue ...terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. Methods In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7–30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. Results Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2·5% vs 3·0%, p=0·1). Two versus 13 (0·03% vs 0·22%, p=0·0020) were permanently disabled; total dead or disabled: 156 versus 190 (2·6% vs 3·2%, p=0·0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 1·6% vs 82/4426 1·9%, risk ratio 0·86 95% CI 0·63–1·18, p=0·35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 1·9% vs 57/1519 3·8%, risk ratio 0·49 95% CI 0·32–0·77, p=0·0013). Interpretation If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. Funding UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).
Data availability and temporal resolution make it challenging to unravel the anatomy (duration and temporal phasing) of the Last Glacial abrupt climate changes. Here, we address these limitations by ...investigating the anatomy of abrupt changes using sub-decadal-scale records from Greenland ice cores. We highlight the absence of a systematic pattern in the anatomy of abrupt changes as recorded in different ice parameters. This diversity in the sequence of changes seen in ice-core data is also observed in climate parameters derived from numerical simulations which exhibit self-sustained abrupt variability arising from internal atmosphere-ice-ocean interactions. Our analysis of two ice cores shows that the diversity of abrupt warming transitions represents variability inherent to the climate system and not archive-specific noise. Our results hint that during these abrupt events, it may not be possible to infer statistically-robust leads and lags between the different components of the climate system because of their tight coupling.
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