Two- versus three-dimensional connectivity testing of first-order queries to semi-algebraic sets

This paper addresses the question whether one can determine the connectivity of a semi-algebraic set in three dimensions by testing the connectivity of a finite number of two-dimensional ``samples'' of the set, where these samples are defined by first-order queries. The question is answered negatively for two classes of first-order queries: cartesian-product-free, and positive one-pass.Comment: corrected minor confusion in Proof of Theorem

Thermal–Mechanical FEM Analyses of a Liquid Rocket Engines Thrust Chamber

The Italian Ministry of University and Research (MIUR) funded the HYPROB Program to develop regeneratively cooled liquid rocket engines. In this type of engine, liquid propellant oxygen–methane is used, allowing us to reach very good performances in terms of high vacuum specific impulse and high thrust-to-weight ratio. The present study focused on the HYPROB final ground demonstrator, which will be able to produce a 30 kN thrust in flight conditions. In order to achieve such a thrust level, very high chamber pressures (up to 50 bar) and consequently high thermal fluxes and gradients are expected inside the thrust chamber. Very complex and high-fidelity numerical FEM models were adopted here to accurately simulate the thermal–mechanical behavior of the thrust chamber cooling channels, accounting for plasticity, creep, and low-cycle fatigue (LCF) phenomena. The aim of the current work was to investigate the main failure phenomena that could occur during the thrust chamber’s service life. Results demonstrated that LCF is the main cause of failure. The corresponding number of loading cycles to failure were calculated accordingly

FEM Substructuring for the Vibrational Characterization of a Petrol Engine

In this work the vibrational behavior of a 4-cylinder, 4-stroke, petrol engine has been simulated by leveraging on a reduced modelling strategy, based on the Component Mode Synthesis (CMS), adopted to reduce the size of the full FEM model of the engine. The FEM model of the engine, comprising all of its sub-components, has been preliminary characterized from the vibrational standpoint; subsequently, the CMS has been adopted in order to reduce the FEM model size. Frequency Response Function (FRF) analyses have been used to identify the resonant frequencies and mode shapes of the different FEM models, and the so-obtained results have been compared showing a very good agreement. The reduced model has been able to reproduce with a high accuracy the vibration response at the engine mounts. The adopted reduced modelling strategy turned out to be effective in lowering the computational burden, keeping, at the same time, an accurate replication of the engine vibrational behavior. Runtimes have been significantly reduced from 24 hours for the full FEM model to less than 2 hours for the reduced model

Passive noise control oriented design of aircraft headrests

Two Passive Noise Control (PNC) concepts were numerically evaluated in terms of their impact on the Sound Pressure Level (SPL) perceived by passengers of an aircraft flight. A concept was based on the shape optimization of the headrests, whereas the second one was based on the adoption of a high absorbing material, i.e. a nanofiber textile, to improve the acoustic performances of the headrests. To this aim, an aircraft seat was modelled with the Boundary Element Method (BEM) and loaded with a spherical distribution of monopole sources surrounding the seat. Different configurations of headrest shape and covering textiles were then compared in terms of the SPL calculated at passengers’ ears. The work shows how an acoustic-oriented design of the aircraft headrests could achieve an average SPL reduction for passengers up to 3 dBA

A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF)

Purpose: To explore pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) ceftazidime-avibactam for treating difficult-to-treat resistant Gram-negative (DTR-GN) infections in critical patients undergoing continuous venovenous haemodiafiltration (CVVHDF). Materials and methods: Patients treated with CI ceftazidime-avibactam for DTR-GN infections during CVVHDF were retrospectively assessed. Ceftazidime and avibactam concentrations were measured at steady-state and the free fraction (fCss) was calculated. Total clearance (CLtot) of both agents were calculated and the impact of CVVHDF intensity was assessed by linear regression. The joint PK/PD target of ceftazidime-avibactam was defined as optimal when both fCss/MIC≥4 for ceftazidime and fCss/CT > 1 for avibactam were achieved. Relationship between ceftazidime-avibactam PK/PD targets and microbiological outcome was assessed. Results: Eight patients with DTR-GN infections were retrieved. Median fCss were 84.5 (73.7–87.7 mg/L) for ceftazidime and 24.8 mg/L (20.7–25.8 mg/L) for avibactam. Median CLtot was 2.39 L/h (2.05–2.96 L/h) for ceftazidime and 2.56 L/h (2.12–2.98 L/h) for avibactam. Median CVVHDF dose was 38.6 mL/h/kg (35.9–40.0 mL/kg/h). CLtot were linearly correlated with CVVHDF dose (r = 0.53;p = 0.03, and r = 0.64;p = 0.006, respectively). The joint PK/PD targets were optimal granting microbiological eradication in all the assessable cases. Conclusion: CI administration of 1.25–2.5 g q8h ceftazidime-avibactam may allow prompt attainment and maintenance of optimal joint PK/PD targets during high-intensity CVVHDF

Understanding the barriers and improving care in type 2 diabetes: Brazilian perspective in time to do more in diabetes

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex disease, particularly in a continental country like Brazil. We attempted to understand and evaluate the perceptions and routines of Brazilians with T2DM and physicians, compared with other countries. METHODS: We compared the results from a 20-min online survey in Brazil with simultaneously collated data from India, Japan, Spain, UK and USA. RESULTS: In total, 652 adults with T2DM and 337 treating physicians were enrolled, of whom 100 patients and 55 physicians were from Brazil. The numbers of primary care physicians from the five countries were 221 versus 43 in Brazil, diabetes specialists were 61 versus 12. There was disconnect between the opinions of physicians and people with diabetes globally. Further, there were differences between clinical practices in Brazil versus the rest of the world, in many areas Brazilians were performing better. CONCLUSIONS: Communication between patients and physicians should be clearer. There is an urgent need to identify the deficits in education, in order to address the clinical inertia within the diabetes management team. There is a necessity to understand the specific requirements of the Brazilian population in order to contextualise international guidelines and implement local changes in practice.The online survey was supported by Novarti

Candida tropicalis fungaemia: incidence, risk factors and mortality in a general hospital

AbstractThe risk factors and clinical features of patients with Candida tropicalis fungaemia have not been fully defined. We performed a case–control study comparing 59 cases of C. tropicalis fungaemia with 177 episodes of fungaemia caused by other species of Candida in our hospital over a 24-year period (January 1985 to December 2008). Patients with C. tropicalis fungaemia were more likely to be older (median age, 67 vs. 56 years; p 0.01), to have cancer (45.5% vs. 31.6%, p 0.04), and to have the abdomen as the portal of entry (32.2% vs. 11.9%, p 0.001), and had a higher in-hospital mortality rate (61% vs. 44%, p 0.03). Multivariate analysis showed that the independent risk factors for C. tropicalis fungaemia were cancer (OR 4.5; 95% CI 1.05–3.83; p 0.03) and the abdomen as the portal of entry (OR 13.6; 95% CI 1.9–8.2; p <0.001). When survivors were compared with non-survivors, the risk factors associated with a poor outcome were neutropenia (19.4% vs. 0; p 0.03), corticosteroid treatment (36% vs. 13%; p 0.07), and septic shock (50% vs. 17.4%; p 0.01). The independent risk factors for mortality in the multivariate analysis were corticosteroid treatment (OR 8.2; 95% CI 0.9–27.7; p 0.04) and septic shock (OR 14.6; 95% CI 2.4–90.2; p 0.004), whereas urinary tract infection (OR 0.07; 95% CI 0.01–0.8; p 0.03) and catheter removal (OR 0.06; 95% CI 0.01–0.4; p 0.002) were protective factors. C. tropicalis is the fourth most common cause of fungaemia in our hospital. It is associated with underlying malignancy, the abdomen as the portal of entry, and poor outcome

A Proof of Concept of the Usefulness of a TDM-Guided Strategy for Optimizing Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Ampicillin-Based Regimens in a Case Series of Patients with Enterococcal Bloodstream Infections and/or Endocarditis

(1) Objective: To describe the usefulness of a real-time therapeutic drug monitoring (TDM)-based strategy for optimizing pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) ampicillin-based regimens in a case series of patients affected by suspected or documented enterococcal bloodstream infections (BSIs) and/or infective endocarditis (IE). (2) Methods: Patients treated with CI ampicillin-based regimens for documented or suspected enterococcal BSI/IE who underwent real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) between June 2021 and May 2022 were retrospectively assessed. Ampicillin concentrations were determined at steady state, and the free fraction (fC(ss)) was calculated according to a plasma protein binding of 20%. The fC(ss)/MIC ratio was selected as the PD parameter for ampicillin efficacy and was defined as optimal for values between 4 and 8. The requirement for TDM-guided ampicillin dosing adjustments was assessed. (3) Results: Data for 12 patients with documented (n = 10) or suspected (n = 2) enterococcal infections (7 with BSIs and 5 with IE) were retrieved. The ampicillin PK/PD target was optimal over time in all of the 10 documented infections. None of the enterococcal BSIs persisted. Following the first real-time TDM-based ECPA, ampicillin dosage was decreased by &gt;50% in 11 out of 12 patients (91.7%). (4) Conclusions: CI may be helpful in attaining aggressive ampicillin PK/PD targets in patients affected by enterococcal BSIs and/or IE. Administration of CI ampicillin after loading coupled with real-time TDM-based ECPA could be a valuable strategy for managing enterococcal infections

DBEM crack propagation for nonlinear fracture problems

A three-dimensional crack propagation simulation is performed by the Dual Boundary Element Method (DBEM). The Stress Intensity Factors (SIFs) along the front of a semi elliptical crack, initiated from the external surface of a hollow axle, are calculated for bending and press fit loading separately and for a combination of them. In correspondence of the latter loading condition, a crack propagation is also simulated, with the crack growth rates calculated using the NASGRO3 formula, calibrated for the material under analysis (steel ASTM A469). The J-integral and COD approaches are selected for SIFs calculation in DBEM environment, where the crack path is assessed by the minimum strain energy density criterion (MSED). In correspondence of the initial crack scenario, SIFs along the crack front are also calculated by the Finite Element (FE) code ZENCRACK, using COD, in order to provide, by a cross comparison with DBEM, an assessment on the level of accuracy obtained. Due to the symmetry of the bending problem a pure mode I crack propagation is realised with no kinking of the propagating crack whereas for press fit loading the crack propagation becomes mixed mode. The crack growth analysis is nonlinear because of normal gap elements used to model the press fit condition with added friction, and is developed in an iterative-incremental procedure. From the analysis of the SIFs results related to the initial cracked configuration, it is possible to assess the impact of the press fit condition when superimposed to the bending load case

Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients.

BACKGROUND: Central nervous system (CNS) infections by human polyomaviruses (HPyVs), with the exception of JC (JCPyV), have been poorly studied. METHODS: In total, 234 cerebrospinal fluid (CSF) samples were collected from patients affected with neurological disorders. DNA was isolated and subjected to quantitative real-time PCR (Q-PCR) for the detection of six HPyVs: JCPyV, BKPyV, Merkel cell PyV (MCPyV), HPyV6, HPyV7, and HPyV9. Where possible, the molecular characterization of the viral strains was carried out by nested PCR and automated sequencing. RESULTS: JCPyV was detected in 3/234 (1.3%), BKPyV in 15/234 (6.4%), MCPyV in 22/234 (9.4%), and HPyV6 in 1/234 (0.4%) CSF samples. JCPyV was detected at the highest (p < 0.05) mean load (3.7 7 107 copies/mL), followed by BKPyV (1.9 7 106 copies/mL), MCPyV (1.9 7 105 copies/mL), and HPyV6 (3.3 7 104 copies/mL). The noncoding control regions (NCCRs) of the sequenced viral strains were rearranged. CONCLUSIONS: HPyVs other than JCPyV were found in the CSF of patients affected with different neurological diseases, probably as bystanders, rather than etiological agents of the disease. However, the fact that they can be latent in the CNS should be considered, especially in immunosuppressed patients