Purpura fulminans (PF) is a highly thrombotic subtype of disseminated intravascular coagulation that can accompany severe bacterial, and more rarely, viral infections. PF is associated with an ...extremely high mortality rate, and patients often die of overwhelming multisystemic thrombosis rather than septic shock. Survivors typically experience amputation of involved extremities and significant scarring in affected areas. Despite the devastating clinical course associated with this hemostatic complication of infection, the mechanism of PF remains poorly understood. Severe acquired deficiency of protein C and dysfunction of the protein C-thrombomodulin pathway as well as other systems that exert a negative regulatory effect on coagulation have been implicated. Management of PF involves treatment of the underlying infection, aggressive anticoagulation, and robust transfusion support aimed at correcting acquired deficiencies in natural anticoagulant proteins. In this review, we address the diagnosis and management of PF with a focus on a rational approach to this condition informed by the available data. Proposed mechanisms underlying the dysregulation of coagulation seen in PF are also covered, and implications for therapy are discussed.
•Purpura fulminans (PF) is a highly thrombotic subtype of DIC resulting from infection.•PF requires prompt recognition and treatment.•Pathophysiology involves dysfunction of endogenous anticoagulant pathways.•Therapy centers on aggressive anticoagulation and factor repletion.
•There are few examples of genomic data being used in conservation biology.•Many uncertainties accompany genomic analyses and interpretations.•We discuss how best to deal with these uncertainties in ...a conservation setting.•We outline why uptake has been difficult for practitioners and offer a solution.
The global loss of biodiversity continues at an alarming rate. Genomic approaches have been suggested as a promising tool for conservation practice as scaling up to genome-wide data can improve traditional conservation genetic inferences and provide qualitatively novel insights. However, the generation of genomic data and subsequent analyses and interpretations remain challenging and largely confined to academic research in ecology and evolution. This generates a gap between basic research and applicable solutions for conservation managers faced with multifaceted problems. Before the real-world conservation potential of genomic research can be realized, we suggest that current infrastructures need to be modified, methods must mature, analytical pipelines need to be developed, and successful case studies must be disseminated to practitioners.
The use of accelerated beams of electrons, protons or ions has furthered the development of nearly every scientific discipline. However, high-energy muon beams of equivalent quality have not yet been ...delivered. Muon beams can be created through the decay of pions produced by the interaction of a proton beam with a target. Such 'tertiary' beams have much lower brightness than those created by accelerating electrons, protons or ions. High-brightness muon beams comparable to those produced by state-of-the-art electron, proton and ion accelerators could facilitate the study of lepton-antilepton collisions at extremely high energies and provide well characterized neutrino beams
. Such muon beams could be realized using ionization cooling, which has been proposed to increase muon-beam brightness
. Here we report the realization of ionization cooling, which was confirmed by the observation of an increased number of low-amplitude muons after passage of the muon beam through an absorber, as well as an increase in the corresponding phase-space density. The simulated performance of the ionization cooling system is consistent with the measured data, validating designs of the ionization cooling channel in which the cooling process is repeated to produce a substantial cooling effect
. The results presented here are an important step towards achieving the muon-beam quality required to search for phenomena at energy scales beyond the reach of the Large Hadron Collider at a facility of equivalent or reduced footprint
.
Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer
. Here we use a systematic approach to study spatial genome integrity in situ and ...describe previously unidentified clonal relationships. We used spatially resolved transcriptomics
to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
A fusion nuclear science facility (FNSF) could play an important role in the development of fusion energy by providing the nuclear environment needed to develop fusion materials and components. The ...spherical torus/tokamak (ST) is a leading candidate for an FNSF due to its potentially high neutron wall loading and modular configuration. A key consideration for the choice of FNSF configuration is the range of achievable missions as a function of device size. Possible missions include: providing high neutron wall loading and fluence, demonstrating tritium self-sufficiency, and demonstrating electrical self-sufficiency. All of these missions must also be compatible with a viable divertor, first-wall, and blanket solution. ST-FNSF configurations have been developed simultaneously incorporating for the first time: (1) a blanket system capable of tritium breeding ratio TBR 1, (2) a poloidal field coil set supporting high elongation and triangularity for a range of internal inductance and normalized beta values consistent with NSTX/NSTX-U previous/planned operation, (3) a long-legged divertor analogous to the MAST-U divertor which substantially reduces projected peak divertor heat-flux and has all outboard poloidal field coils outside the vacuum chamber and superconducting to reduce power consumption, and (4) a vertical maintenance scheme in which blanket structures and the centerstack can be removed independently. Progress in these ST-FNSF missions versus configuration studies including dependence on plasma major radius R0 for a range 1 m-2.2 m are described. In particular, it is found the threshold major radius for TBR = 1 is R0 1.7 m, and a smaller R0 = 1 m ST device has TBR 0.9 which is below unity but substantially reduces T consumption relative to not breeding. Calculations of neutral beam heating and current drive for non-inductive ramp-up and sustainment are described. An A = 2, R0 = 3 m device incorporating high-temperature superconductor toroidal field coil magnets capable of high neutron fluence and both tritium and electrical self-sufficiency is also presented following systematic aspect ratio studies.
Batrachochytrium dendrobatidis is a fungus belonging to the Phylum Chytridiomycota, Class Chytridiomycetes, Order Chytridiales, and is the highly infectious aetiological agent responsible for a ...potentially fatal disease, chytridiomycosis, which is currently decimating many of the world's amphibian populations. The fungus infects 2 amphibian orders (Anura and Caudata), 14 families and at least 200 species and is responsible for at least 1 species extinction. Whilst the origin of the agent and routes of transmission are being debated, it has been recognised that successful management of the disease will require effective sampling regimes and detection assays. We have developed a range of unique sampling protocols together with diagnostic assays for the detection of B. dendrobatidis in both living and deceased tadpoles and adults. Here, we formally present our data and discuss them in respect to assay sensitivity, specificity, repeatability and reproducibility. We suggest that compliance with the recommended protocols will avoid the generation of spurious results, thereby providing the international scientific and regulatory community with a set of validated procedures which will assist in the successful management of chytridiomycosis in the future.
Justify your alpha Lakens, Daniel; Adolfi, Federico G.; Albers, Casper J. ...
Nature human behaviour,
2018, Letnik:
2, Številka:
3
Journal Article
Recenzirano
Odprti dostop
In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, ...including the alpha level.
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