A penalisation approach to simulate root compressors

The simulation of the unsteady flow field in root compressors requires to deal with several challenges related to the presence of moving parts and complex geometries. In the present work a penalisation approach applied to the compressible Navier- Stokes equations is investigated as a possible technique to perform this kind of simulations. In particular, the compressible Navier- Stokes equations are augmented by source terms which represent the effects of the body on the fluid and then they are integrated in both the fluid and solid domains. The presence of moving bodies is taken into account by a level set function. A validation based on a grid convergence study is performed on the flow around an impulsively started cylinder. A preliminary simulation of the flow field inside a root compressor is performed in order to predict the unsteady mass flow rate through the machine

Aortic arch rupture after multiple multilayer stent treatment of a thoracoabdominal aneurysm

Despite the improvement in diagnostic and therapeutic strategies, the treatment of thoracoabdominal aneurysms is still burdened with a high incidence of peri/postoperative morbidity and mortality. The multilayer flow modulator is a new and promising technique for the treatment of such disease; however, some limits are still evident. We report the case of a 76-year-old woman affected by a symptomatic thoracoabdominal aneurysm treated with multiple Cardiatis multilayer flow modulators complicated by aortic arch rupture on the fifth postoperative day, with subsequent patient death

An MILP approach for the optimal design of renewable battery-hydrogen energy systems for off-grid insular communities

Abstract The optimal sizing of stand-alone renewable H2-based microgrids requires the load demand to be reliably satisfied by means of local renewable energy supported by a hybrid battery/hydrogen storage unit, while minimizing the system costs. However, this task is challenging because of the high number of components that have to be installed and operated. In this work, an MILP optimization framework has been developed and applied to the off-grid village of Ginostra (on the Stromboli island, Italy), which is a good example of several other insular sites throughout the Mediterranean area. A year-long time horizon was considered to model the seasonal storage, which is necessary for off-grid areas that wish to achieve energy independence by relying on local renewable sources. The degradation costs of batteries and H2-based devices were included in the objective function of the optimization problem, i.e., the annual cost of the system. Efficiency and investment cost curves were considered for the electrolyzer and fuel cell components in order to obtain a more detailed and precise techno-economic estimation. The design optimization was also performed with the inclusion of a general demand response program (DRP) to assess its impact on the sizing results. Moreover, the effectiveness of the proposed MILP-based method was tested by comparing it with a more traditional approach, based on a metaheuristic algorithm for the optimal sizing complemented with ruled-based strategies for the system operation. Thanks to its longer-term storage capability, hydrogen is required for the optimal system configuration in order to reach energy self-sufficiency. Finally, considering the possibility of load deferral, the electricity generation cost can be reduced to an extent that depends on the amount of load that is allowed to participate in the DRP scheme. This cost reduction is mainly due to the decreased capacity of the battery storage system

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the stemness marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease

Calibration method and performance of a time-of-flight detector to measure absolute beam energy in proton therapy

Background: The beam energy is one of the most significant parameters in particle therapy since it is directly correlated to the particles' penetration depth inside the patient. Nowadays, the range accuracy is guaranteed by offline routine quality control checks mainly performed with water phantoms, 2D detectors with PMMA wedges, or multi-layer ionization chambers. The latter feature low sensitivity, slow collection time, and response dependent on external parameters, which represent limiting factors for the quality controls of beams delivered with fast energy switching modalities, as foreseen in future treatments. In this context, a device based on solid-state detectors technology, able to perform a direct and absolute beam energy measurement, is proposed as a viable alternative for quality assurance measurements and beam commissioning, paving the way for online range monitoring and treatment verification. Purpose: This work follows the proof of concept of an energy monitoring system for clinical proton beams, based on Ultra Fast Silicon Detectors (featuring tenths of ps time resolution in 50 μm active thickness, and single particle detection capability) and time-of-flight techniques. An upgrade of such a system is presented here, together with the description of a dedicated self-calibration method, proving that this second prototype is able to assess the mean particles energy of a monoenergetic beam without any constraint on the beam temporal structure, neither any a priori knowledge of the beam energy for the calibration of the system. Methods: A new detector geometry, consisting of sensors segmented in strips, has been designed and implemented in order to enhance the statistics of coincident protons, thus improving the accuracy of the measured time differences. The prototype was tested on the cyclotron proton beam of the Trento Protontherapy Center (TPC). In addition, a dedicated self-calibration method, exploiting the measurement of monoenergetic beams crossing the two telescope sensors for different flight distances, was introduced to remove the systematic uncertainties independently from any external reference. Results: The novel calibration strategy was applied to the experimental data collected at TPC (Trento) and CNAO (Pavia). Deviations between measured and reference beam energies in the order of a few hundreds of keV with a maximum uncertainty of 0.5 MeV were found, in compliance with the clinically required water range accuracy of 1 mm. Conclusions: The presented version of the telescope system, minimally perturbative of the beam, relies on a few seconds of acquisition time to achieve the required clinical accuracy and therefore represents a feasible solution for beam commission, quality assurance checks, and online beam energy monitoring

Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: a phase 1/2 trial of the European MCL network (SAKK 36/13).

BACKGROUND The Bruton's tyrosine kinase inhibitor ibrutinib and the proteasome inhibitor bortezomib have single-agent activity, non-overlapping toxicities, and regulatory approval in mantle cell lymphoma (MCL). In vitro, their combination provides synergistic cytotoxicity. In this investigator-initiated phase 1/2 trial, we established the recommended phase 2 dose of ibrutinib in combination with bortezomib, and assessed its efficacy in patients with relapsed or refractory MCL. METHODS In this phase 1/2 study open in 15 sites in Switzerland, Germany and Italy, patients with relapsed or refractory MCL after ≤2 lines of chemotherapy and both ibrutinib-naïve and bortezomib-naïve received six cycles of ibrutinibb and bortezomib, followed by ibrutinib maintenance. For the phase 1 study, a standard 3 + 3 dose escalation design was used to determine the recommended phase 2 dose of ibrutinib in combination with bortezomib. The primary endpoint in phase 1 was the dose limiting toxicities in cycle 1. The phase 2 study was an open-label, single-arm trial with a Simon's two-stage min-max design, with a primary endpoint of overall response rate (ORR) assessed by CT/MRI. This study was registered with ClinicalTrials.gov, NCT02356458. FINDINGS Between August 2015 and September 2016, nine patients were treated in the phase 1 study, and 49 patients were treated between November 2016 and March 2020 in the phase 2 of the trial. The ORR was 81.8% (90% CI 71.1, 89.8%, CR(u) 21.8%) which increased with continued ibrutinib (median 10.6 months) to 87.3%, (CR(u) 41.8%). 75.6% of patients had at least one high-risk feature (Ki-67 > 30%, blastoid or pleomorphic variant, p53 overexpression, TP53 mutations and/or deletions). In these patients, ibrutinib and bortezomib were also effective with an ORR of 74%, increasing to 82% during maintenance. With a median follow-up of 25.4 months, the median duration of response was 22.7, and the median PFS was 18.6 months. PFS reached 30.8 and 32.9 months for patients with a CR or Cru, respectively. INTERPRETATION The combination of ibrutinib and bortezomib shows durable efficacy in patients with relapsed or refractory MCL, also in the presence of high-risk features. FUNDING SAKK (Hubacher Fund), Swiss State Secretariat for Education, Research and Innovation, Swiss Cancer Research Foundation, and Janssen

Early progression as a predictor of survival in marginal zone lymphomas: An analysis from the FIL-NF10 study

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome inMZL and identifies a high-risk population