Identification of the hysteretic behaviour of a partial-strength steel-concrete moment-resisting frame structure subject to pseudodynamic tests

n/

A hysteretic multiscale formulation for nonlinear dynamic analysis of composite materials

This article has been made available through the Brunel Open Access Publishing Fund.A new multiscale finite element formulation is presented for nonlinear dynamic analysis of heterogeneous structures. The proposed multiscale approach utilizes the hysteretic finite element method to model the microstructure. Using the proposed computational scheme, the micro-basis functions, that are used to map the microdisplacement components to the coarse mesh, are only evaluated once and remain constant throughout the analysis procedure. This is accomplished by treating inelasticity at the micro-elemental level through properly defined hysteretic evolution equations. Two types of imposed boundary conditions are considered for the derivation of the multiscale basis functions, namely the linear and periodic boundary conditions. The validity of the proposed formulation as well as its computational efficiency are verified through illustrative numerical experiments

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

SKELETAL MUSCLE MITOCHONDRIAL REMODELING AND AUTOPHAGY ACTIVATION IN HIGH FAT FED AND EXERCISE TRAINED MICE

S. Ehrlicher1, S. Dasari2, S. Newsom1, M. Robinson1 1Oregon State University, Corvallis, OR;2Mayo Clinic, Rochester, MN PURPOSE: Changes to the mitochondrial proteome are implicated in insulin resistance and are regulated in part by autophagy, which is activated by exercise and suppressed by nutrients. We investigated the remodeling of the mitochondrial proteome in response to high fat feeding including sensitivity of autophagy to nutrients and requirement of exercise induced autophagy for metabolic flexibility. METHODS: Insulin resistance was induced in C57BL/6J mice (WT) using 12 weeks of high-fat (HF) compared to low-fat (LF) diet. Proteomic identification by mass spectrometry was performed on mitochondria isolated from the gastrocnemius in HF versus LF fed mice. The ability for nutrients to suppress accumulation of the autophagy marker LC3II was determined during intravenous infusion of saline, hyperinsulinemia with euglycemia or hyperglycemia with hyperinsulinemia (n=7-10). The requirement of autophagy for metabolic adaptations to exercise was assessed using a mouse model that cannot induce autophagy with exercise (BCL) versus WT control. LF and HF diet mice performed eight weeks of treadmill training then respiratory exchange ratio (RER) was measured during 24 hours of feeding or fasting (n=3-5). RESULTS: The abundance of 40 mitochondrial proteins was greater (fold change \u3e 0.5 and p\u3c0.05) in HF mice compared to LF mice, primarily in pathways of β-oxidation. Despite insulin resistance to glucose metabolism, autophagy activation was similar between diet groups during hyperglycemic-hyperinsulinemic conditions (HF, LC3II = 0.04 ±0.02; LF, LC3II = 0.03 ±0.01) but was lower (p\u3c0.05) than saline (HF, LC3II = 0.08 ±0.04; LF, LC3II = 0.06 ±0.03). BCL and WT mice had similar RER values following exercise training that reflected the LF diet (WT, RER = 0.94 ±0.01; BCL, RER = 0.93 ±0.03) and HF diet (WT, RER = 0.76 ±0.004; BCL, RER = 0.76 ±0.01). Additionally, all mice were able to shift to lipid oxidation during fasting (LF WT, RER = 0.71 ±0.01; LF BCL, RER = 0.72 ±0.01; HF WT, RER = 0.72 ±0.004; HF BCL, RER = 0.72 ±0.003). CONCLUSION: Insulin resistance shifted the mitochondrial proteome to greater β-oxidation capacity and did not change suppression of autophagy to insulin and glucose, but may impair the sensitivity of autophagy to insulin. The lack of autophagy activation during exercise did not impede whole body metabolic flexibility. Funding: K01DK103829 to MM

Comparison of restoring force models for the identification of structures with hysteresis and degradation

When subjected to events such as earthquakes, engineering structures typically exhibit a nonlinear and hysteretic behaviour with stiffness and strength degradations. Though a reliable evaluation of safety conditions should take into account the nonlinear dynamic and evolutionary nature of the structural response, the experimental identification of a nonlinear behaviour under dynamic and seismic loading is, to date, an open problem. The present research aims at evaluating the potential of different restoring force models for simulating the seismic response of hysteretic structural systems, with special emphasis on the two main problems encountered when applying this approach to full-scale structures under intense excitation: (a) a markedly time-dependent behaviour; (b) need to compare among different restoring force models, either expressed in a parametric or polynomial form. In particular, polynomial models will be formulated both in terms of restoring force and its derivative, in order to present a comprehensive discussion of different strategies. The nonlinear identification technique employed in this paper is required to account for a time-dependent behaviour. In fact, in presence of degradation or any other time-varying characteristics, instantaneous identification certainly constitutes an enhancement of the classical restoring force based approach, and may as well provide checks on the consistency of the assumed models