Experimental and Numerical Investigation of a Lattice Structure for Energy Absorption: Application to the Design of an Automotive Crash Absorber

In this work, an experimental and numerical analysis of a lattice structure for energy absorption was carried out. The goal was to identify the most influencing parameters of the unit cell on the crushing performances of the structure, thus guiding the design of energy absorbers. Two full factorial plans of compression tests on cubic specimens of carbon nylon produced by fused deposition modeling (FDM) were performed. The factors were the beam diameter and the number of unit cells. In the first factorial plan, the specimen volume is constant and the dimensions of the unit cell are varied, while the second factorial plan assumes a constant size of the unit cell and the volume changes in accordance with their number. The results showed that the specific energy absorption increases with the diameter of the beam and decreases with the size of the unit cell. Based on these results, a crash absorber for the segment C vehicle was designed and compared with the standard component of the vehicle made of steel. In addition to a mass reduction of 25%, the improved crushing performances of the lattice structure are shown by the very smooth force-displacement curve with limited peaks and valleys

Single-lap joints of similar and dissimilar adherends bonded with a polyurethane adhesive used in the automotive industry

The mechanical performances of single-lap joints between similar and dissimilar adherends bonded with a bi-component polyurethane adhesive have been studied in the present work. The substrate materials include both carbon fibre reinforced composite material (CRFP) and painted metal substrates (PMS). The following substrate combinations were tested: CFRP/CFRP, PMS/PMS, and CFRP/PMS. Two adhesive overlaps, 12 mm and 24 mm, with a fixed thickness were studied to assess the mechanical behaviour of the adhesive joints. The experimental results have been used to construct a finite element model of the single lap joint tests. The objective is to determine the material cohesive properties, in particular the maximum shear stress and the corresponding energy release rate, of the adhesive layer for each retained combination of substrates. An optimization scheme based on transient nonlinear finite element analysis has been here considered, where cohesive parameters of the adhesive layer are handled as design variables. Material parameters are firstly identified for the 12 mm overlap, minimizing the discrepancy between the experimental and numerical force-displacement curves. Then, to validate the obtained properties, results of the 24 mm overlap single lap joint tests are used. The comparison between the experimental and numerical results shows a very good agreemen

Assessment of residual elastic properties of a damaged composite plate with combined damage index and finite element methods

In structural component applications the use of composite materials is increasing thanks to their optimal mechanical characteristics. However, the complexity of the damage evolution in composite materials significantly limits their widespread diffusion. Non-destructive tests are thus becoming ever more important. The detecting Damage Index (DId) technique has been recently brought in the realm of the non-destructive characterization tests for components made of composite material. In contrast to other techniques, this methodology allows to quantitatively assess local residual properties. In this paper, the DId technique is adopted in combination with the finite element method. The mechanical response of two composite plates (an 8-layer twill fabric carbon/epoxy) subjected to four-point bending test is firstly used to tune a finite element model of the laminate. Then, an undamaged laminate of the same composite material is progressively damaged through repeated four-point bending tests. Local residual elastic properties are mapped on the plate through the DId technique. A continuous polynomial curve has been considered to account for the variation of the elastic modulus in the finite element model. The resulting force-displacement curve of the numerical analysis is compared to experimental data of damaged plate, resulting in very good agreement. The combination of the experimental activity and the numerical finite element analysis points out the accuracy of the DId methodology in assessing local residual elastic properties of composite materials

Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives

Epidermal growth factor receptor (EGFR) inhibitors are valuable therapeutics in metastatic colorectal cancer (mCRC). Anti-EGFR monoclonal antibodies (MoAbs), such as cetuximab or panitumumab, in combination with chemotherapy are effective treatment options for patients with RAS and BRAF wild-type mCRC. Nevertheless, several issues are still open concerning the optimal use of anti-EGFR drugs in the continuum of care of mCRC. Novel approaches for increasing the efficacy of anti-EGFR therapies include better molecular selection of EGFR-dependent mCRC, intensification of chemotherapy, combination of anti-EGFR MoAbs and immune checkpoint inhibitors, and reintroduction of EGFR blockade or 'rechallenge' in selected patients who have previously responded to anti-EGFR MoAb therapy. An extensive translational research program was conducted in the Cetuximab After Progression in KRAS wIld-type colorectal cancer patients-Gruppo Oncologico dell' Italia Meridionale (CAPRI-GOIM) study with the aims of determining which subgroups of patients could benefit from the continuous inhibition of EGFR, from evaluating the role of liquid biopsy-based and its concordance with tissue-based molecular testing, and from investigating novel potential mechanisms of resistance to anti-EGFR therapies. In this review, we summarize the translational and clinical findings of the CAPRI-GOIM program in the context of the current knowledge of therapeutic strategies and of ongoing research on more appropriate uses of anti-EGFR therapies in RAS and BRAF wild-type mCRC patients

RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

BACKGROUND: High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. METHODS: Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m(2) and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. RESULTS: Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P 0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P < .001) were independent predictors of CI-AKI. Pulmonary edema occurred in 4 patients (1%). Potassium replacement was required in 16 patients (4%). No patients developed severe hypomagnesemia, hyponatremia, or hypernatremia. CONCLUSIONS: RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention

Early triple negative breast cancer: Conventional treatment and emerging therapeutic landscapes

Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline-and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of the recent advances in the management of early stage TNBC and focused on the latest emerging biomarkers and their clinical application to select the best therapeutic strategy in this hard-to-treat population

axl has a prognostic role in metastatic colorectal cancer mcrc and is a predictive biomarker of lack of efficacy of chemotherapy ct cetuximab in ras wild type wt patients pts

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Incidence and predictors of heart failure hospitalization and death in permanent pacemaker patients: a single-centre experience over medium-term follow-up

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Plant-Made Bet v 1 for Molecular Diagnosis

Allergic disease diagnosis is currently experiencing a breakthrough due to the use of allergenic molecules in serum-based assays rather than allergen extracts in skin tests. The former methodology is considered a very innovative technology compared with the latter, since it is characterized by flexibility and adaptability to the patient’s clinical history and to microtechnology, allowing multiplex analysis. Molecular-based analysis requires pure allergens to detect IgE sensitization, and a major goal, to maintain the diagnosis cost-effective, is to limit their production costs. In addition, for the production of recombinant eukaryotic proteins similar to natural ones, plant-based protein production is preferred to bacterial-based systems due to its ability to perform most of the post-translational modifications of eukaryotic molecules. In this framework, Plant Molecular Farming (PMF) may be useful, being a production platform able to produce complex recombinant proteins in short time-frames at low cost. As a proof of concept, PMF has been exploited for the production of Bet v 1a, a major allergen associated with birch (Betula verrucosa) pollen allergy. Bet v 1a has been produced using two different transient expression systems in Nicotiana benthamiana plants, purified and used in a new generation multiplex allergy diagnosis system, the patient-Friendly Allergen nano-BEad Array (FABER). Plant-made Bet v 1a is immunoreactive, binding IgE and inhibiting IgE-binding to the Escherichia coli expressed allergen currently available in the FABER test, thus suggesting an overall similar though non-overlapping immune activity compared with the E. coli expressed form

Vulnerability to low-dose combination of irinotecan and niraparib in ATM-mutated colorectal cancer

Background: Despite the advancements in new therapies for colorectal cancer (CRC), chemotherapy still constitutes the mainstay of the medical treatment. For this reason, new strategies to increase the efficacy of chemotherapy are desirable. Poly-ADP-Ribose Polymerase inhibitors (PARPi) have shown to increase the activity of DNA damaging chemotherapeutics used in the treatment of CRC, however previous clinical trials failed to validate these results and pointed out dose-limiting toxicities that hamper the use of such combinations in unselected CRC patients. Nevertheless, in these studies little attention was paid to the mutational status of homologous recombination repair (HRR) genes. Methods: We tested the combination of the PARPi niraparib with either 5-fluorouracil, oxaliplatin or irinotecan (SN38) in a panel of 12 molecularly annotated CRC cell lines, encompassing the 4 consensus molecular subtypes (CMSs). Synergism was calculated using the Chou-Talalay method for drug interaction. A correlation between synergism and genetic alterations in genes involved in homologous recombination (HR) repair was performed. We used clonogenic assays, mice xenograft models and patient-derived 3D spheroids to validate the results. The induction of DNA damage was studied by immunofluorescence. Results: We showed that human CRC cell lines, as well as patient-derived 3D spheroids, harboring pathogenic ATM mutations are significantly vulnerable to PARPi/chemotherapy combination at low doses, regardless of consensus molecular subtypes (CMS) and microsatellite status. The strongest synergism was shown for the combination of niraparib with irinotecan, and the presence of ATM mutations was associated to a delay in the resolution of double strand breaks (DSBs) through HRR and DNA damage persistence. Conclusions: This work demonstrates that a numerically relevant subset of CRCs carrying heterozygous ATM mutations may benefit from the combination treatment with low doses of niraparib and irinotecan, suggesting a new potential approach in the treatment of ATM-mutated CRC, that deserves to be prospectively validated in clinical trials