Generation of Entanglement Outside of the Light Cone

The Feynman propagator has nonzero values outside of the forward light cone. That does not allow messages to be transmitted faster than the speed of light, but it is shown here that it does allow entanglement and mutual information to be generated at space-like separated points. These effects can be interpreted as being due to the propagation of virtual photons outside of the light cone or as a transfer of pre-existing entanglement from the quantum vacuum. The differences between these two interpretations are discussed.Comment: 25 pages, 7 figures. Additional references and figur

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Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities

The COVID-19 pandemic is a global public health crisis, with considerable mortality and morbidity exerting pressure on health-care resources, including critical care. An excessive host inflammatory response in a subgroup of patients with severe COVID-19 might contribute to the development of acute respiratory distress syndrome (ARDS) and multiorgan failure. Timely therapeutic intervention with immunomodulation in patients with hyperinflammation could prevent disease progression to ARDS and obviate the need for invasive ventilation. Granulocyte macrophage colony-stimulating factor (GM-CSF) is an immunoregulatory cytokine with a pivotal role in initiation and perpetuation of inflammatory diseases. GM-CSF could link T-cell-driven acute pulmonary inflammation with an autocrine, self-amplifying cytokine loop leading to monocyte and macrophage activation. This axis has been targeted in cytokine storm syndromes and chronic inflammatory disorders. Here, we consider the scientific rationale for therapeutic targeting of GM-CSF in COVID-19-associated hyperinflammation. Since GM-CSF also has a key role in homoeostasis and host defence, we discuss potential risks associated with inhibition of GM-CSF in the context of viral infection and the challenges of doing clinical trials in this setting, highlighting in particular the need for a patient risk-stratification algorithm

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

A low density of 0.8 g/cc for the Trojan binary asteroid 617 Patroclus

The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees). The asteroid 617 Patroclus is the only known binary Trojan (Merline et al. 2001). The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system centre of mass, describing roughly a circular orbit. Using the orbital parameters, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8 g/cc. The components of Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the solar system.Comment: 10 pages, 3 figures, 1 tabl

Symptoms after Ingestion of Pig Whipworm Trichuris suis Eggs in a Randomized Placebo-Controlled Double-Blind Clinical Trial

Symptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3rd dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was ≤14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation

On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models

[EN] In order to be reusable, history-based feature-based parametric CAD models must reliably allow for modifications while maintaining their original design intent. In this paper, we demonstrate that relations that fix the location of geometric entities relative to the reference system produce inflexible profiles that reduce model reusability. We present the results of an experiment where novice students and expert CAD users performed a series of modifications in different versions of the same 2D profile, each defined with an increasingly higher number of fix geometric constraints. Results show that the amount of fix constraints in a 2D profile correlates with the time required to complete reusability tasks, i.e., the higher the number of fix constraints in a 2D profile, the less flexible and adaptable the profile becomes to changes. In addition, a pilot software tool to automatically track this type of constraints was developed and tested. Results suggest that the detection of fix constraint overuse may result in a new metric to assess poor quality models with low reusability. The tool provides immediate feedback for preventing high semantic level quality errors, and assistance to CAD users. Finally, suggestions are introduced on how to convert fix constraints in 2D profiles into a negative metric of 3D model quality.The authors would like to thank Raquel Plumed for her support in the statistical analysis. This work has been partially funded by Grant UJI-A02017-15 (Universitat Jaume I) and DPI201784526-R (MINECO/AEI/FEDER, UE), project CAL-MBE. The authors also wish to thank the editor and reviewers for their valuable comments and suggestions that helped us improve the quality of the paper.González-Lluch, C.; Company, P.; Contero, M.; Pérez Lopez, DC.; Camba, JD. (2019). On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models. 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