Design Tools for Bolted End-Plate Beam-to-Column Joints

Predicting the response of beam-to-column joints is essential to evaluate the response of moment frames. The well-known component method is based on a mechanical modelling of the joint, through joint subdivision into more elementary components subsequently reassembled together to obtain the whole joint characteristics. Significant advantages of the component method are the following: (i) the mechanics-based modelling approach; (ii) the easier general characteristics of components. However, the method is commonly perceived by practicing engineers as being too laborious for practical applications. Within this context, this paper summarizes the results of a theoretical study aiming to develop simplified analysis tools for bolted end-plate beam-to-column joints, based on the Eurocode 3 component method. The accuracy of the component method was first evaluated, by comparing theoretical predictions of the plastic resistance and initial stiffness with corresponding experimental data collected from the available literature. Subsequently, design/analysis charts were developed through a parametric application of the component method by means of automatic calculation tools. They are easy and quick tools to be used in the first phases of the design process, in order to identify joint configurations and geometrical properties satisfying specified joint structural performances. The parametric analysis allowed also identifying further simplified analytical tools, in the form of nondimensional equations for predicting quickly the joint structural properties. With reference to selected geometries, the approximate equations were verified to provide sufficiently accurate predictions of both the stiffness and the resistance of the examined beam-to-column joints

Comparison between percutaneous and laparoscopic microwave ablation of hepatocellular carcinoma

Background: Based on patient and tumor characteristics, some authors favor laparoscopic microwave ablation (LMWA) over the percutaneous approach (PMWA) for treatment of hepatocellular carcinoma (HCC). We compared the two techniques in terms of technique efficacy, local tumor progression (LTP) and complication rates. Study design: A retrospective comparative analysis was performed on 91 consecutive patients (102 HCC tumors) who underwent PMWA or LMWA between October 2014 and May 2019. Technique efficacy at one-month and LTP at follow-up were assessed by contrast-enhanced CT/MRI. Kaplan–Meier estimates and Cox regression were used to compare LTP-free survival (LTPFS). Results: At baseline analysis, LMWA group showed higher frequency of multinodular disease (p < .001) and average higher energy delivered over tumor size (p = .033); PMWA group showed higher rates of non-treatment-naïve patients (p = .001), patients with Hepatitis-C (p = .03) and BCLC-A1 disease (p = .006). Technique efficacy was not significantly different between the two groups (p = .18). Among effectively treated patients, 75 (83 tumors) satisfied ≥6 months follow-up, 54 (57 tumors) undergoing PMWA and 21 (26 tumors) LMWA. LTP occurred in 14/83 cases (16.9%): 12 after PMWA (21.1%) and 2 after LMWA (7.7%). At univariate analysis, technique did not correlate to LTPFS (p = .28). Subgroup analysis showed a trend toward worse LTPFS after PMWA of subcapsular tumors (p = .16). Major complications were observed in six patients (6.6%), 2 after PMWA and 4 after LMWA (3.2% vs 14.3%, p = .049). Conclusions: Technical approach did not affect LTPFS. Complications were reported more frequently after LMWA. Despite higher complication rates, LMWA seems a valid option for treatment of subcapsular tumors

Metabolomic alterations do not induce metabolic burden in the industrial yeast M2n[pBKD2-Pccbgl1]-C1 engineered by multiple δ-integration of a fungal β-glucosidase gene

CITATION: Favaro L., et al. 2019. Metabolomic alterations do not induce metabolic burden in the industrial yeast M2n[pBKD2-Pccbgl1]-C1 engineered by multiple d-integration of a fungal b-glucosidase gene. Frontiers in Bioengineering and Biotechnology. 7:376. doi:10.3389/fbioe.2019.00376The original publication is available at https://www.frontiersin.org/articles/10.3389/fbioe.2019.00376/fullIn the lignocellulosic yeast development, metabolic burden relates to redirection of resources from regular cellular activities toward the needs created by recombinant protein production. As a result, growth parameters may be greatly affected. Noteworthy, Saccharomyces cerevisiae M2n[pBKD2-Pccbgl1]-C1, previously developed by multiple d-integration of the b-glucosidase BGL3, did not show any detectable metabolic burden. This work aims to test the hypothesis that the metabolic burden and the metabolomic perturbation induced by the d-integration of a yeast strain, could differ significantly. The engineered strain was evaluated in terms of metabolic performances and metabolomic alterations in different conditions typical of the bioethanol industry. Results indicate that the multiple d-integration did not affect the ability of the engineered strain to grow on different carbon sources and to tolerate increasing concentrations of ethanol and inhibitory compounds. Conversely, metabolomic profiles were significantly altered both under growing and stressing conditions, indicating a large extent of metabolic reshuffling involved in the maintenance of the metabolic homeostasis. Considering that four copies of BGL3 gene have been integrated without affecting any parental genes or promoter sequences, deeper studies are needed to unveil the mechanisms implied in these metabolomic changes, thus supporting the optimization of protein production in engineered strains.Padova Universityhttps://www.frontiersin.org/articles/10.3389/fbioe.2019.00376/fullPublisher’s versio

Fingerprints as Predictors of Schizophrenia: A Deep Learning Study

Background and hypothesis: The existing developmental bond between fingerprint generation and growth of the central nervous system points to a potential use of fingerprints as risk markers in schizophrenia. However, the high complexity of fingerprints geometrical patterns may require flexible algorithms capable of characterizing such complexity. Study design: Based on an initial sample of scanned fingerprints from 612 patients with a diagnosis of non-affective psychosis and 844 healthy subjects, we have built deep learning classification algorithms based on convolutional neural networks. Previously, the general architecture of the network was chosen from exploratory fittings carried out with an independent fingerprint dataset from the National Institute of Standards and Technology. The network architecture was then applied for building classification algorithms (patients vs controls) based on single fingers and multi-input models. Unbiased estimates of classification accuracy were obtained by applying a 5-fold cross-validation scheme. Study results: The highest level of accuracy from networks based on single fingers was achieved by the right thumb network (weighted validation accuracy = 68%), while the highest accuracy from the multi-input models was attained by the model that simultaneously used images from the left thumb, index and middle fingers (weighted validation accuracy = 70%). Conclusion: Although fitted models were based on data from patients with a well established diagnosis, since fingerprints remain lifelong stable after birth, our results imply that fingerprints may be applied as early predictors of psychosis. Specially, if they are used in high prevalence subpopulations such as those of individuals at high risk for psychosis.This work was supported by several grants funded by the Instituto de Salud Carlos III and the Spanish Ministry of Science and Innovation (co-funded by the European Regional Development Fund/European Social Fund “Investing in your future”): Miguel Servet Research Contract (CPII13/00018 to RS, CPII16/00018 to EP-C, CP20/00072 to MF-V), PFIS Contract (FI19/0352 to MG-R). Research Mobility programme (MV18/00054 to EP-C), Research Projects (PI18/00877 and PI21/00525 to RS). It has also been supported by the Centro de Investigación Biomédica en Red de Salud Mental and the Generalitat de Catalunya: 2014SGR1573 and 2017SGR1365 to EP-C and SLT008/18/00206 to IF-R from the Departament de Salut. The authors have declared that there are no conflicts of interest in relation to the subject of this study.S

Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units

Purpose: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods: In this retrospective–prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55–69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89–175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil–lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion: Daily values or trends over time of parameters associated with acute organ dysfunction, acid–base derangement, coagulation impairment, or systemic inflammation were associated with patient survival

Safety of extended interval dosing immune checkpoint inhibitors:a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.</p