Cytokine release syndrome in COVID-19 patients, a new scenario for an old concern. The fragile balance between infections and autoimmunity

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk

A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement

A Fourier transform for sheaves on Lagrangian families of real tori

We systematically develop a transform of the Fourier-Mukai type for sheaves on symplectic manifolds $X$ of any dimension fibred in Lagrangian tori. One obtains a bijective correspondence between unitary local systems supported on Lagrangian submanifolds of $X$ and holomorphic vector bundles with compatible unitary connections supported on complex submanifolds of the relative Jacobian of $X$ (suitable conditions being verified on both sides).Comment: Latex, 30 pages (in a4wide format), no figures. v2: Minor expository changes, typos corrected. v3: Final version to appear in two parts in J. Geom. Phy

A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement

Sisters in structure but different in character, some benzaldehyde and cinnamaldehyde derivatives differentially tune Aspergillus flavus secondary metabolism

Great are the expectations for a new generation of antimicrobials, and strenuous are the research efforts towards the exploration of diverse molecular scaffolds—possibly of natural origin – aimed at the synthesis of new compounds against the spread of hazardous fungi. Also high but winding are the paths leading to the definition of biological targets specifically fitting the drug’s structural characteristics. The present study is addressed to inspect differential biological behaviours of cinnamaldehyde and benzaldehyde thiosemicarbazone scaffolds, exploiting the secondary metabolism of the mycotoxigenic phytopathogen Aspergillus flavus. Interestingly, owing to modifications on the parent chemical scaffold, some thiosemicarbazones displayed an increased specificity against one or more developmental processes (conidia germination, aflatoxin biosynthesis, sclerotia production) of A. flavus biology. Through the comparative analysis of results, the ligand-based screening strategy here described has allowed us to delineate which modifications are more promising for distinct purposes: from the control of mycotoxins contamination in food and feed commodities, to the environmental management of microbial pathogens, to the investigation of specific structure–activity features for new generation drug discovery

An 81-Year-Old Man with a 6-Year History of Chronic Lymphocytic Leukemia Presenting with Disease Flare Following Ibrutinib Discontinuation

Patient: Male, 81-year-old Final Diagnosis: Chronic lymphocytic leukemia Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Hematology Objective: Background: Case Report: Conclusions: Unusual clinical course Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm and the most common leukemia in adults in Western countries. Novel agents, including BTK inhibitors and the BCL2 inhibitor venetoclax, have dramati-cally changed the treatment landscape. Moreover, a disease flare, characterized by sudden worsening of clinical symptoms, radiographic findings of rapidly worsening splenomegaly or lymphadenopathy, and laboratory changes (increased absolute lymphocyte count or lactate dehydrogenase), is a phenomenon described in up to 25% of patients with CLL after ibrutinib discontinuation. We describe a patient with CLL with disease flare after ibrutinib discontinuation due to disease progression and describe the subsequent management of vene-toclax initial treatment in the course of the disease flare. We describe the case of an 81-year-old man with a 6-year history of CLL who was treated with multiple lines of therapy and developed worsening of disease-related signs and symptoms with fever, marked increase of lym-phocyte count, acute worsening of renal function, and increase in lymph nodes and spleen size following ces-sation of targeted therapy with ibrutinib at the time of disease progression. There was subsequent overlap-ping of ibrutinib during the venetoclax dose escalation period to prevent disease flare recurrence. Our report highlights the problem of disease flare after ibrutinib discontinuation in order to avoid associated patient morbidity, underscoring the importance of awareness of this phenomenon and focusing on the addition of venetoclax at time of progression in ibrutinib-treated patients, as a temporary overlap strategy, to prevent disease flare

The machine protection system for the ELI-NP gamma beam system

The new Gamma Beam System (GBS) of the ELI-NPproject [1], currently under installation in Magurele (RO)by INFN, as part of EuroGammas consortium, can providegamma rays that open new possibilities for nuclear photonicsand nuclear physics.ELI-NP gamma rays are produced by Compton back-scattering to get monochromaticity (0,1% bandwidth), highflux (1013photons), tunable direction and energy up to19.5 MeV. Such gamma beam is obtained when a high-intensity laser collides a high-brightness electron beam withenergies up to740 MeV, a repetition rate of100 Hz, withtrains of 32 bunches within the same RF bucket.An advanced Machine Protection System (MPS) has beendeveloped, in order to ensure proper operation for this chal-lenging facility. The MPS operates on different layers of thecontrol system and is interfaced with all its sub-systems. Forinstance, it comprises different kind of beam loss monitors(based on Cherenkov optical fiber), hall probes, fast currenttransformer together with BPMs, and an embedded systembased on FPGA with distributed I/O over EtherCAT, to mon-itor vacuum and RF systems [2], which require fast responseto be interlocked within one RF pulse

Beam manipulation for resonant plasma wakefield acceleration

Plasma-based acceleration has already proved the ability to reach ultra-high accelerating gradients. However the step towards the realization of a plasma-based accelerator still requires some e ff ort to guarantee high brightness beams, stability and reliability. A significant improvement in the efficiency of PWFA has been demonstrated so far accelerating a witness bunch in the wake of a higher charge driver bunch. The transformer ratio, therefore the energy transfer from the driver to the witness beam, can be increased by resonantly exciting the plasma with a properly pre-shaped drive electron beam. Theoretical and experimental studies of beam manipulation for resonant PWFA will be presented her

The Birth of a Hawaiian Fissure Eruption

Most basaltic explosive eruptions intensify abruptly, allowing little time to document processes at the start of eruption. One opportunity came with the initiation of activity from fissure 8 (F8) during the 2018 eruption on the lower East Rift Zone of Klauea, Hawaii. F8 erupted in four episodes. We recorded 28 minutes of high-definition video during a 51-minute period, capturing the onset of the second episode on 5 May. From the videos we were able to analyze the following in-flight parameters: frequency and duration of explosions; ejecta heights; pyroclast exit velocities; in-flight total mass and estimated mass eruption rates; and the in-flight total grain size distributions. Videos record a transition from initial pulsating outgassing, via spaced, but increasingly rapid, discrete explosions, to quasi-sustained, unsteady fountaining. This transition accompanied waxing intensity (mass flux) of the F8 eruption. We infer that all activity was driven by a combination of the ascent of a coupled mixture of small bubbles and melt, and the buoyant rise of decoupled gas slugs and/or pockets. The balance between these two types of concurrent flow determined the exact form of the eruptive activity at any point in time, and changes to their relative contributions drove the transition we observed at early F8. Qualitative observations of other Hawaiian fountains at Klauea suggest that this physical model may apply more generally. This study demonstrates the value of in-flight parameters derived from high resolution videos, which offer a rapid and highly time-sensitive alternative to measurements based on sampling of deposits post-eruption

Delivery status of the ELI-NP gamma beam system

International audienceThe ELI-NP GBS is a high intensity and monochromatic gamma source under construction in Magurele (Romania). The design and construction of the Gamma Beam System complex as well as the integration of the technical plants and the commissioning of the overall facility, was awarded to the Eurogammas Consortium in March 2014. The delivery of the facility has been planned in for 4 stages and the first one was fulfilled in October 31st 2015. The engineering aspects related to the delivery stage 1 are presented