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A 68–year–old Caucasian male, post–Bentall procedure with a bioprosthetic valve following extensive aortic dissection involving the ascending aorta and aortic arch, presented to the Emergency Department with persistent fever for over a month. During his hospitalization, he experienced ventricular fibrillation in the setting of hypokalemia, successfully managed with Advanced Cardiovascular Life Support (ACLS) and DC shock, leading to the restoration of sinus rhythm. Subsequently, he was admitted to the Cardiovascular Intensive Care Unite. Blood tests revealed neutrophilic leukocytosis with elevated inflammatory markers, anemia, and a troponin curve consistent with myocardial injury in the context of sepsis and anemia. Echocardiography demonstrated a left ventricle of normal dimensions with globally depressed function (EF 45%), attributed to apical akinesia. The prosthetic valve was functioning normally, and there were no signs of endocarditic vegetations or pericardial involvement. A transesophageal echocardiogram confirmed the absence of vegetations. Given echocardiographic signs of myocardial ischemia, coronary angiography was performed, revealing a coronary circulation free from significant stenosis. Cultural exams showed positivity for Enterococcus faecalis. A PET–CT revealed the presence of radioisotope uptake around the vascular prosthesis situated in the aortic arch. An Infectious Disease specialist recommended antibiotic therapy with Piperacillin/Tazobactam and Teicoplanin. At the one–month follow–up, the patient remained asymptomatic, free from new febrile episodes. The follow–up echocardiogram indicated improved global systolic function, and inflammatory markers remained consistently negative. Repeat blood cultures were negative. This case illustrates a suspected endocarditis on a prosthetic valve where both transthoraci and transesophageal echocardiography yielded negative results. The use of PET–CT, on the other hand, revealed the presence of vascular graft infection, proving to be a valuable method in this clinical setting.

A 56–year–old Caucasian woman with a silent cardiac history, a history of smoking, and a previous hip prosthesis surgery presented to the emergency department. She reported oppressive chest pain radiating to the left arm intermittently for about 2 days, precipitated by significant emotional stress at work. The 12–lead ECG revealed sinus bradycardia, symmetrically negative T waves in the anterolateral leads, and prolonged QTc interval (544 ms). The echocardiogram showed apical akinesia, basal hyperkinesia, and moderately depressed global systolic function (ejection fraction 45%). Laboratory tests indicated elevated myocardial necrosis enzyme levels (hs–TnI 549 pg/ml), negative inflammatory markers, normal electrolytes, hemogram within normal limits, and normal renal function. She was admitted with a working diagnosis of NSTEMI–ACS. On admission, the patient was asymptomatic for angina, and had stable vital signs, particularly a blood pressure of 120/70 mmHg and a heart rate of 55 bpm. Clinical examination revealed no abnormalities. The InterTAK score was 67. Coronary angiography revealed severe stenosis of the mid–left anterior descending coronary artery, treated with PTCA–DES. The intracoronary imaging (OCT) showed a plaque with characteristics of stability, leading to the consideration of the diagnosis of Takotsubo syndrome in patient with CAD. Subsequent echocardiography showed nearly complete recovery of systolic function. At the one–month follow–up, the patient exhibited preserved systolic function (EF 60%). This case highlights Takotsubo syndrome with concomitant coronary artery disease (CAD) as a bystander. According to Mayo Clinic criteria, the coexistence of severe CAD would exclude the diagnosis of Takotsubo. However, recent studies suggest the potential for coexistence, prompting the need for additional imaging modalities such as OCT and CMR to differentiate culprit from bystander lesions. Utilizing these techniques may alter the prevalence of Takotsubo syndrome, necessitating a reassessment of cases initially classified as NSTEMI–ACS.

An in situ diagnostic for verifying the spectral phase of an intense laser pulse at focus is presented. This diagnostic relies on measuring the effect of optical compression on ionization-induced blueshifting of the laser spectrum. Experimental results from the Berkeley Lab Laser Accelerator, a laser source rigorously characterized by conventional techniques, are presented and compared with simulations to illustrate the utility of this technique. These simulations show distinguishable effects from second-, third-, and fourth-order spectral phase.

Laser-plasma accelerators (LPAs) are capable of accelerating charged particles to very high energies in very compact structures. In theory, therefore, they offer advantages over conventional, large-scale particle accelerators. However, the energy gain in a single-stage LPA can be limited by laser diffraction, dephasing, electron-beam loading and laser-energy depletion. The problem of laser diffraction can be addressed by using laser-pulse guiding and preformed plasma waveguides to maintain the required laser intensity over distances of many Rayleigh lengths; dephasing can be mitigated by longitudinal tailoring of the plasma density; and beam loading can be controlled by proper shaping of the electron beam. To increase the beam energy further, it is necessary to tackle the problem of the depletion of laser energy, by sequencing the accelerator into stages, each powered by a separate laser pulse. Here, we present results from an experiment that demonstrates such staging. Two LPA stages were coupled over a short distance (as is needed to preserve the average acceleration gradient) by a plasma mirror. Stable electron beams from a first LPA were focused to a twenty-micrometre radius—by a discharge capillary-based active plasma lens—into a second LPA, such that the beams interacted with the wakefield excited by a separate laser. Staged acceleration by the wakefield of the second stage is detected via an energy gain of 100 megaelectronvolts for a subset of the electron beam. Changing the arrival time of the electron beam with respect to the second-stage laser pulse allowed us to reconstruct the temporal wakefield structure and to determine the plasma density. Our results indicate that the fundamental limitation to energy gain presented by laser depletion can be overcome by using staged acceleration, suggesting a way of reaching the electron energies required for collider applications.

• Portable, quasi-static particle-in-cell code method for plasma acceleration. • Orders-of-magnitude speedup over CPU implementation exploiting fast GPU computing. • Speedup obtained with optimized memory management and exploiting efficient GPU FFTs. • Scalability to hundreds of cutting-edge GPU with a novel parallelization method. • Open-repository, well-documented implementation based on the AMReX framework. Modeling plasma accelerators is a computationally challenging task and the quasi-static particle-in-cell algorithm is a method of choice in a wide range of situations. In this work, we present the first performance-portable, quasi-static, three-dimensional particle-in-cell code HiPACE++. By decomposing all the computation of a 3D domain in successive 2D transverse operations and choosing appropriate memory management, HiPACE++ demonstrates orders-of-magnitude speedups on modern scientific GPUs over CPU-only implementations. The 2D transverse operations are performed on a single GPU, avoiding time-consuming communications. The longitudinal parallelization is done through temporal domain decomposition, enabling near-optimal strong scaling from 1 to 512 GPUs. HiPACE++ is a modular, open-source code enabling efficient modeling of plasma accelerators from laptops to state-of-the-art supercomputers. Program Title: HiPACE++ CPC Library link to program files: https://doi.org/10.17632/zh3rc7hvrm.1 Developer's repository link: HiPACE++ GitHub repository Licensing provisions: BSD 3-clause Programming language: C++ Nature of problem: Modeling plasma accelerators is a computationally challenging task requiring nanometer-scale resolutions over meter-scale propagation distances. The quasi-static particle-in-cell method enables high-fidelity simulations of this strongly non-linear process, but these simulations can be very expensive. Solution method: The quasi-static particle-in-cell algorithm is modified to enable efficient utilization of accelerated hardware, in particular with GPU computing, reducing the cost of simulations by orders of magnitude. A novel longitudinal parallelization enables excellent strong scaling of this method up to hundreds of GPUs. Reference: 10.5281/zenodo.5358483 [ABSTRACT FROM AUTHOR]

Generation of high intensity and well collimated multi energetic proton beams from laser-matter interaction extend the possibility to use protons as a diagnostic to image imploding target in Inertial Confinement Fusion experiments. An experiment was done at the Rutherford Appleton Laboratory (Vulcan Laser Petawatt laser) to study fast electron propagation in cylindrically compressed targets, a subject of interest for fast ignition. This was performed in the framework of the experimental road map of HiPER (the European High Power laser Energy Research facility Project). In the experiment, protons accelerated by a ps-laser pulse were used to radiograph a 220 m diameter cylinder (20 m wall, filled with low density foam), imploded with 200 J of green laser light in 4 symmetrically incident beams of pulse length 1 ns. Point projection proton backlighting was used to get the compression history and the stagnation time. Detailed comparison with 2D numerical hydro simulations has been done using a Monte Carlo code adapted to describe multiple scattering and plasma effects and with those from hard X-ray radiography. These analysis shows that due to the very large mass densities reached during implosion processes, protons traveling through the target undergo a very large number of collisions which deviate protons from their original trajectory reducing proton radiography resolution. Here we present a simple analytical model to study the proton radiography diagnostic performance as a function of the main experimental parameters such as proton beam energy and target areal density. This approach leads to define two different criteria for PR resolution (called "strong" and "weak" condition) describing different experimental conditions. Finally numerical simulations using both hydrodynamic and Monte Carlo codes are presented to validate analytical predictions.

Abstract: We present a numerical scheme to solve the fully 3D Maxwell–Vlasov equations. The aim is to investigate the interaction of a laser pulse with a plasma and the acceleration of electrons and ions. We choose the approach based on numerical particles to approximate the distribution function interpreted, according to the Klimontovich formalism, as a probability distribution function. The key points are a high order implicit scheme to approximate the space differential operators and a time evolution scheme of adequate accuracy. [Copyright &y& Elsevier]

Abstract: We show that with an eighth order scheme the dispersion relation is very accurately reproduced and the numerical Cherenkov effect is small so that a good isotropy is obtained for the phase velocity. The comparison with an exact solution for the Gaussian wave packet confirms the accuracy of the method. The evolution of particles in the plane wave field is considered and an analysis of the first integrals of motion confirm the accuracy of the characteristics of the distribution function. [Copyright &y& Elsevier]

Male to female sex reversal results from failure of testis development. Mutations in the SRYgene or in other genes involved in the sexual differentiation pathway are considered to cause XY gonadal dysgenesis. The majority of the mutations in the SRYdescribed so far are located within the SRYcoding region, mainly in the HMG-box conserved domain. Comparison of 5′ flanking SRYgene sequences among different species indicated the presence of several putative conserved consensus sequences for different transcription regulators. In this study, we investigated a 360 bp sequence encompassing the SRYputative core promoter, in 17 patients with variable degrees of 46,XY sex reversal, which have been previously shown not to bear mutations in the SRYcoding region. Sequencing analysis of the SRYpromoter in one patient with complete XY gonadal dysgenesis revealed a three base pair deletion in one of the Sp1 binding sites. The deletion abolished Sp1 binding in vitro.This is the first report on a naturally occurring mutation affecting the Sp1 regulatory element in the SRYpromoter region, which is associated with sex reversal. Additionally, upon familial investigation the father, who had 18 genital surgeries due to severe hypospadia without cryptorchidism, was found to bear the same deletion and several relatives were referred to have sexual ambiguity.

Goals of workProspective clinical study to evaluate patients suffering from solid tumor using a totally implanted venous access device (TIVAD) to determine: (1) if there is a relationship between cutaneous contamination at port insertion site and catheter-related bloodstream infection (CRBI); (2) development modalities of CRBI; (3) if there is a relationship between chemotherapy administration modalities by push/bolus versus continuous infusion and CRBI.Patients and methodsWe studied 41 consecutive patients who needed a TIVAD positioned for chemotherapy administration by bolus/push or continuous infusion. In every patient, we performed blood cultures from blood samples from port catheters and cutaneous cultures from cutaneous tampons of the skin surrounding the implant area on the first (T0) and eight day (T1) postoperatively, after 1 month (T2), and after 3 months (T3) from insertion.Main resultsThe study was completed on 40 patients; in one case, the port was removed at T2 for septic complications. We obtained four positive blood cultures (two, 5%), two in the same patient, all caused by staphylococcus. Positive cutaneous tampons were 21 (13%) in 11 patients (27%); the four CRBI occurred in this group of patients with none in the remaining 30 patients (73%) for a total number of 120 tampons ( p<0.01). In two cases, the same germ was isolated from both the skin and blood. None of the patients presented a local infection of the subcutaneous pocket. Positive cutaneous cultures decrease over time: T0–T2, 24–5%; T1–T3, 20–5% ( p<0.04). There were no differences in CRBI incidence and positive cutaneous tampons between the two chemotherapy administration modalities.ConclusionsCutaneous microbial flora has a primary role in CRBI development within TIVADs; there is a relationship between cutaneous colonization and CRBI; colonization reaches its maximum during the first days after catheterization in which the use of the system is at high risk; colonization occurs both via extraluminal and endoluminal routes; there is no difference in CRBI incidence between bolus and continuous infusion administration.

Meropenem, a new carbapenem antibiotic, was assessed to evaluate its effects on some functional parameters of human polymorphonuclear (PMN) and natural killer (NK) cells in comparison with imipenem/cilastatin. Both drugs significantly inhibited PMN phagocytosis and chemotaxis at concentrations of 2,000 and 4,000 μg/ml. They affected PMN microbicidal activity, evaluated against Candida albicans, only at 4,000 μg/ml. A study of the effects of both drugs on peripheral NK populations and the human NK line (NK-92) showed that even at 4,000 μg/ml there was no effect on antitumor activity. These data indicate that meropenem can reduce some PMN antimicrobial functions only at very high concentrations like imipenem/cilastatin, whereas no concentration influenced NK activity.

AbstractWe measured the parameter reproducibility and radial electron density profile of capillary discharge waveguides with diameters of 650 $\mathrm{\mu} \mathrm{m}$to 2 mm and lengths of 9 to 40 cm. To the best of the authors’ knowledge, 40 cm is the longest discharge capillary plasma waveguide to date. This length is important for $\ge$10 GeV electron energy gain in a single laser-driven plasma wakefield acceleration stage. Evaluation of waveguide parameter variations showed that their focusing strength was stable and reproducible to $<0.2$% and their average on-axis plasma electron density to $<1$%. These variations explain only a small fraction of laser-driven plasma wakefield acceleration electron bunch variations observed in experiments to date. Measurements of laser pulse centroid oscillations revealed that the radial channel profile rises faster than parabolic and is in excellent agreement with magnetohydrodynamic simulation results. We show that the effects of non-parabolic contributions on Gaussian pulse propagation were negligible when the pulse was approximately matched to the channel. However, they affected pulse propagation for a non-matched configuration in which the waveguide was used as a plasma telescope to change the focused laser pulse spot size.

Coronatine is a phytotoxin produced by some plant-pathogenic bacteria. It has been shown that coronatine mimics the action of methyl jasmonate (MeJA) in plants. MeJA is a plant-signaling molecule involved in stress responses such as wounding and pathogen attack. In Arabidopsis thaliana, MeJA is essential for pollen grain development. The coi1 (for coronatine-insensitive) mutant of Arabidopsis, which is insensitive to coronatine and MeJA, produces sterile male flowers and shows an altered response to wounding. When the differential display technique was used, a message that was rapidly induced by coronatine in wild-type plants but not in coi1 was identified and the corresponding cDNA was cloned. The coronatine-induced gene ATHCOR1 (for A. thaliana coronatine-induced) is expressed in seedlings, mature leaves, flowers, and siliques but was not detected in roots. The expression of this gene was dramatically reduced in coi1 plants, indicating that COI1 affects its expression. ATHCOR1 was rapidly induced by MeJA and wounding in wild-type plants. The sequence of ATHCOR1 shows no strong homology to known proteins. However, the predicted polypeptide contains a conserved amino acid sequence present in several bacterial, animal, and plant hydrolases and includes a potential ATP/GTP-binding-site motif (P-loop).

Summary: Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days.Although we found a three- to fivefold pharmaco-kinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6–14 days of continuous use). Two-thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters.Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks. Use of individual pharmacokinetic information, instead of population parameters, may account for superior performance characteristic of this computer-assisted continuous drug infusion system.

According to Wortmann classification, the Building Industry (BI) can be defined as engineer-to-order (ETO) industry: the engineering-process starts only when an order is acquired. This definition implies that every final product (building) is almost unique' and processes cannot be easily standardized or automated. Because of this, BI is one of the less efficient industries today' mostly leaded by craftsmanship. In the last years' several improvements in process efficiency have been made focusing on manufacturing and installation processes only. In order to improve the efficiency of design and engineering processes as well, the scientific community agrees that the most fruitful strategy should be Front-End Design (FED). Nevertheless, effective techniques and tools are missing. This paper discusses outcomes of a research activity that aims at highlighting whether Parametric and Generative Design techniques allow reducing wastes of resources and improving the overall efficiency of the BI, by pushing the Digitalization of design and engineering processes of products. Focusing on the Glued-Laminated-Timber industry, authors will show how Parametric and Generative Design techniques can be introduced in a standard supply-chain system, highlighting potentials and criticism on the supply-chain system as a whole.