The geometric paradigm in computational elasto-plasticity

Computational methods, for large displacements of continua in the elastoplastic range, rely on the mathematical modeling of the nonlinear constitutive behavior. In last decades an increasing favor has been deserved to nonlinear models based on a chain decomposition of the deformation gradient. The troubles involved in a structural analysis based on this model are well-known and have not been overcome although many efforts devoted to this end. Our investigation towards a more satisfactory model starts from the new analysis of the rate elastic behavior performed in [1, 2] since the difficulties faced by previous formulations were the very motivation for the discard of rate constitutive models in elasto-plasticity [3]. The new definition of hypo-elasticity, the detection of simple integrability conditions and a new formulation of conservativeness, lead to a definition of rate elasticity suitable for an effective modeling of rate elasto-plastic constitutive behaviors [4]. The treatment is based on a geometric definition of spatial and material fields and on the statement of a geometric paradigm assessing the rules for comparison of material fields naturally provided by push-pull according to the relevant transformation. The rates involved in constitutive relations are Lie-derivatives of stress field and constitutive parameters. Geometric compatibility requires that elastic and plastic stretchings additively give the Lie-derivative of metric field. No privileged reference configuration is involved and no consequent multiplicative decomposition of deformation gradient is assumed. Computational methods are shown to be based on the pull-back of constitutive relations to a straightened out trajectory segment which plays the role of computation chamber wherein linear operations of differentiation and integration may be performed. Accordingly, finite elastic and plastic stretches are considered as purely computational tools with no physical interpretation in constitutive relations. Both 3-D and lower dimensional structural models, such as wires and membranes, may be analysed by a direct application of the theory. The outcome is a significant improvement of physical insight and computational effectiveness with respect to previous treatments of finite elasto-plasticity

On torsion of nonlocal Lam strain gradient FG elastic beams

Abstract The nonlocal strain gradient theory of elasticity is the focus of numerous studies in literature. Eringen's nonlocal integral convolution and Lam's strain gradient model are unified by a variational methodology which leads to well-posed structural problems of technical interest. The proposed nonlocal Lam strain gradient approach is presented for functionally graded (FG) beams under torsion. Static and dynamic responses are shown to be significantly affected by size effects that are assessed in terms of nonlocal and gradient length parameters. Analytical elastic rotations and natural frequencies are established by making recourse to a simple solution procedure which is based on equivalence between integral convolutions and differential equations supplemented with variationally consistent (but non-standard) nonlocal boundary conditions. Effects of Eringen's nonlocal parameter and stretch and rotation gradient parameters on the torsional behavior of FG nano-beams are examined and compared with outcomes in literature. The illustrated methodology is able to efficiently model both stiffening and softening torsional responses of modern composite nano-structures by suitably tuning the small-scale parameters

Analytical Solutions of Viscoelastic Nonlocal Timoshenko Beams

A consistent nonlocal viscoelastic beam model is proposed in this paper. Specifically, a Timoshenko bending problem, where size-and time-dependent effects cannot be neglected, is investigated. In order to inspect scale phenomena, a stress-driven nonlocal formulation is used, whereas to simulate time-dependent effects, fractional linear viscoelasticity is considered. These two approaches are adopted to develop a new Timoshenko bending model. Analytical solutions and application samples of the proposed formulation are presented. Moreover, in order to show influences of viscoelastic and size effects on mechanical response, parametric analyses are provided. The contributed results can be useful for the design and optimization of small-scale devices exhibiting flexural behaviour

Predictive factors in GEP-NEN: The integrated role of Ki67, beta-catenin and morphology

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Desenvolvimento de um modelo de identidade de marca para indicações geográficas:uma aplicação à IG Matas de Rondônia.

A Indicação Geográfica (IG) da região Matas de Rondônia para Robustas Amazônicos, do tipo denominação de origem (DO), é a primeira sustentável da espécie Coffea canephora do mundo. Este registro inseriu Rondônia, no mapa das regiões produtoras de cafés especiais do Brasil, conferindo credibilidade ao grão produzido com critérios de qualidade e oferecendo nova oportunidade para a agricultura familiar na Amazônia, uma vez que a base da cafeicultura da região é familiar. Com o registro da IG concedido pelo INPI (Brasil) em 1º de junho de 2021, os cafés denominados Robustas Amazônicos passaram a ter um diferencial de origem e qualidade

The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study

Background and objectives: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral glucosamine sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2×2 factorial design. Methods: A total of 407 overweight (BMI ≥ 27 kg/m2) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) glucosamine sulfate + no DEP (GS, N = 102), and (4) DEP + glucosamine sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero-anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline glucosamine sulfate 1500 mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of ≥1 mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. Results: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with glucosamine sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2×2 factorial design allowed analysis of patients receiving glucosamine sulfate (= 204) vs. those not receiving it (= 203), similarly for those on the DEP (= 203) or not (= 204). Glucosamine sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. Conclusions: Glucosamine sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss

Microenvironment and tumor inflammatory features improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms

Microenvironment-related immune and inflammatory markers, when combined with established Ki-67 and morphology parameters, can improve prognostic prediction in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Therefore, we evaluated the prognostic value of microenvironment and tumor inflammatory features (MoTIFs) in GEP-NENs. For this purpose, formalin-fixed paraffin-embedded tissue sections from 350 patients were profiled by immunohistochemistry for immune, inflammatory, angiogenesis, proliferation, NEN-, and fibroblast-related markers. A total of 314 patients were used to generate overall survival (OS) and disease-free survival (DFS) MoTIFs prognostic indices (PIs). PIs and additional variables were assessed using Cox models to generate nomograms for predicting 5-year OS and DFS. A total of 36 patients were used for external validation of PIs and nomograms' prognostic segregations. From our analysis, G1/G2 versus G3 GEP-NENs showed phenotypic divergence with immune-inflammatory markers. HLA, CD3, CD8, and PD-1/PD-L1 IHC expression separated G3 into two sub-categories with high versus low adaptive immunity-related features. MoTIFs PI for OS based on COX-2Tumor(T) > 4, PD-1Stromal(S) > 0, CD8S < 1, and HLA-IS < 1 was associated with worst survival (hazard ratio [HR] 2.50; 95% confidence interval [CI], 2.12–2.96; p < 0.0001). MoTIFs PI for DFS was based on COX-2T > 4, PD-1S > 4, HLA-IS < 1, HLA-IT < 2, HLA-DRS < 6 (HR 1.77; 95% CI, 1.58–1.99; p < 0.0001). Two nomograms were developed including morphology (HR 4.83; 95% CI, 2.30–10.15; p < 0.001) and Ki-67 (HR 11.32; 95% CI, 5.28–24.24; p < 0.001) for OS, and morphology (PI = 0: HR 10.23; 95% CI, 5.67–18.47; PI = 5: HR 2.87; 95% CI, 1.21–6.81; p < 0.001) and MoTIFs PI for DFS in well-differentiated GEP-NENs (HR 6.21; 95% CI, 2.52–13.31; p < 0.001). We conclude that G1/G2 to G3 transition is associated with immune-inflammatory profile changes; in fact, MoTIFs combined with morphology and Ki-67 improve 5-year DFS prediction in GEP-NENs. The immune context of a subset of G3 poorly differentiated tumors is consistent with activation of adaptive immunity, suggesting a potential for responsiveness to immunotherapy targeting immune checkpoints

Favorable outcome of SARS-CoV-2 infection in pediatric hematology oncology patients during the second and third pandemic waves in Italy: a multicenter analysis from the Infectious Diseases Working Group of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)

COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis