Analysing time dependent problems

Inverse analysis for time dependent problems is discussed i n this chapter. When time dependent processes are analysed, further uncertainties c ome from initial conditions as well as from time dependent boundary conditions and loads , in addition to model parameters. Inverse modelling techniques have been specifi cally developed for this class of problems, which exploit the availability of a set of measurement and/or mon- itoring data at given locations at subsequent time instants . Sequential Bayesian data assimilation is introduced, and a brief review of filtering t echniques is given. In fil- tering the problem unknown is the time evolution of the proba bility density function of the system state, described by means of appropriate time d ependent variables and time invariant parameters, conditioned to all previous obs ervations. Particle filtering is chosen to conceptually illustrate the methodology, by me ans of two simple introduc- tory examples

The role of health technology assessment bodies in shaping drug development.

This is the final version of the article. Available from the publisher via the DOI in this record.The use of health technology assessment (HTA) to inform policy-making is established in most developed countries. Compared to licensing agencies, HTA agencies have different interests and, therefore, different evidence requirements. Criteria for coverage or reimbursement decisions on pharmaceutical compounds vary; however, it is common to include, as part of the HTA, a comparative effectiveness evaluation. This type of clinical data might go beyond that required for market authorization, thus creating an additional evidence gap between the regulatory and the reimbursement submission. The relevance of submissions to HTA agencies is consistently increasing in a pharmaceutical company's perspective, as market prospects are strongly influenced by third-party payers' coverage. In this study, we aim to describe current HTA activities with a potential impact throughout the drug development process of pharmaceuticals, with a comparative emphasis on the systems in place in Italy and in the UK. Based on an extensive literature and website review, we identified three major classes of HTA activities, beyond mainstream HTA, with the potential to influence the drug development program: 1) horizon scanning and early HTA; 2) bipartite and tripartite early dialogue between manufacturers, regulators, and HTA assessors; and 3) managed market entry agreements. From early stages of clinical research up to postauthorization studies, there is a trend toward increased collaboration between parties, anticipation of market access evidence collection, and postmarketing risk-sharing. Heterogeneity of HTA practices increases the complexity of the market access environment. Overall, there are signals that market access departments are gaining importance in the pharmaceutical companies, but there is still a lack of evidence and reporting on how the increasing relevance of HTA has reshaped the way clinical development is designed and managed

Numerical investigation of the equipment set-up in triaxial testing of soft soils

Element testing of soft soils is challenging due to the large strains attained in the pre-failure range. Besides the heterogeneity of natural samples, the set-up configuration is the main driving factor for non-homogenous response. Stress, strain and pore pressure non-uniformities induced by the loading system affect the observed behaviour and complicate proper interpretation of the results. Among the difficulties encountered in the interpretation of laboratory data, the unexpected decrease of the stress ratio frequently observed on Dutch organic soft clays on the wet side of critical state is investigated by numerically back-analysing the triaxial test set-up. A 3D finite element simulation using an advanced constitutive model for soft clays developed at TU Delft was performed to clarify the nature of the response. The results indicate that a decrease in the deviatoric stress up to critical state may be interpreted as a true feature of the soil response. However, the response at large strains is very much influenced by the triaxial shear apparatus, in particular, by the rotation of the top cap which triggers geometrical instability. Practical recommendations are given to limit the effects of the set-up configuration on the determination of the undrained shear strength to be used for field applications

Consequences of drying on the hydro-mechanical response of fibrous peats upon compression

Peats are encountered in waterlogged deltaic areas, where degradation is delayed by favourable environmental conditions. The recent increase in frequency and severity of droughts is expected to accelerate peat degradation, in turn increasing subsidence and flood risk, urging better understanding of the response of peats to drying events. To this aim, compression tests on natural and reconstituted peat samples were performed, supported by X-ray micro-computed tomography. The peat fabric was found to be the key factor in the response to drying, with fibres playing the most significant role. Drying in peats starts affecting the macro-fabric, with an irreversible reduction in volume and disruption of the fibrous network occurring under saturated conditions until a threshold void ratio is reached, below which desaturation occurs of the intra-fibres and intra-peds pores. The first drying stage dramatically decreases the compressibility, while the hydraulic conductivity is hardly affected due to the enlargement of macropores. Secondary compressibility is affected by the peat fabric besides the organic content. The total organic content does not change substantially during drying; hence, it is not the best proxy to describe the consequences of drying on the response of fibrous peats. The fibre content can be better used to serve the aim

A laboratory investigation on an undisturbed silty sand from a slope prone to landsliding

A laboratory investigation is presented for undisturbed samples of a silty sand under saturated conditions. The soil was sampled from test pits south of Rüdlingen in North–East Switzerland, where a landslide triggering experiment was carried out on a steep forest slope. The aim of the work was to characterise the behaviour of the soil in triaxial tests, in the light of the possible failure mechanisms of the slope. Conventional drained and undrained triaxial tests were conducted to detect critical state conditions as well as peak shear strength as a function of confining pressure. Soil specimens were also exposed to stress paths simulating in situ water pressure increase to study the stress–strain response and to enhance the ability to predict failure conditions more accurately in the future. Possible unstable response along the stress paths analysed was investigated by means of second order work and strain acceleration. The results show that temporary unstable conditions may be encountered for this soil at stress ratios below ultimate failure and even below critical state line, depending on void ratio, drainage conditions and time dependent compressibility. A modified state parameter is explored as a potentially useful tool to discriminate conditions leading to eventual collapse

Multi-scale Modelling of Natural Composites Using Thermodynamics-Based Artificial Neural Networks and Dimensionality Reduction Techniques

Modelling natural composites, as the majority of real geomaterials, requires facing their intrinsic multiscale nature. This allows to consider multiphysics coupling occurring at the microscale, then reflected onto the macroscopic behavior. Geotechnics is constantly requiring reliable constitutive models of natural compolve large-scale engineering problems accurately and efficiently. This need motivates the contribution. To capture in detail the macroscopic effects of microssites to socopic processes, many authors have developed multi-scale numerical schemes. A common drawback of such methods is the prohibitive computational cost. Recently,Machine Learning based approaches have raised as promising alternatives to traditional methods. Artificial Neural Networks – ANNs – have been used to predict the constitutive behaviour of complex, heterogeneous materials, with reduced calculation costs. However, a major weakness of ANN is the lack of a rigorous framework based on principles of physics. This often implies a limited capability to extrapolate values ranging outside the training set and the need of large, high-quality datasets, on which performing the training. This work focuses on the use of Thermodynamics-based Artificial Neural Networks – TANN – to predict the constitutive behaviour of natural composites. Dimensionality reduction techniques – DRTs – are used to embed information of microscopic processes into a lower dimensional manifold. The obtained set of variables is used to characterize the state of the material at the macroscopic scale. Entanglement of DRTs with TANN allows to reproduce the complex nonlinear material response with reduced computational costs and guarantying thermodynamic admissibility. To demonstrate the method capabilities an application to a heterogeneous material model is presented

Beyond internet as tool: A mixed-methods study of online drug discussion

This thesis describes how internet use has shaped drug practices among Australians who engage in the recreational use of psychostimulants and hallucinogens (‘party drugs’) and participate in public internet forums. This thesis uniquely contributes to drugs research by applying theoretical frameworks from internet studies, finding that internet forums enable the consumption and production of drug information, facilitate the production of alternative online places, and are increasingly converged with offline social worlds

Preliminary experimental investigation into the use of recycled fibres from textile waste for the improvement of embankments

Failures that occurred in the last few decades highlighted the need to raise awareness about the emergent risk related to the impact localised degradation phenomena have on embankments. Common interventions aimed to improve embankments, such as the reconstruction of the damaged area or the injection of low-pressure grouts to fill fractures and burrows, may cause the weakening of the structure due to discontinuities between natural and treated zones. Moreover, since such repair techniques require huge volumes of materials, more sustainable solutions are encouraged. At the same time, the textile and fashion industries are looking for sustainable waste management and disposal strategies to face environmental problems concerned with the voluminous textile waste dispatched to landfills or incinerators. The use of soil mixed with textile waste in embankment improvement has been investigated to identify an effective engineering practice and to provide a strategy for the circular economy of textiles. Preliminary laboratory tests have been conducted on soil specimens collected from the Secchia River embankment, Northern Italy, to define the appropriate mixture proportions and to compare physical properties and hydro-mechanical behaviour of natural and treated soils. The results show that an appropriate fibre content offers manageable and relatively homogeneous mixtures. The indluence on soil consistency is mainly due to the textile fibre hydrophilic nature. The addition of fibres reduces the maximum dry density and increases the optimum water content. At low stress levels, the compressibility and hydraulic conductivity appear higher, however macro voids produced during sample preparation may alter the findings

NUMERICAL EVALUATION OF THE TEMPORAL VARIATION OF VIBRATIONS INDUCED BY UNDERGROUND TRAINS

The change in the dynamic response of shallow soils as caught by two geophysical test campaigns is exploited to numerically predict the variation in the ground borne vibrations induced by the passage of underground trains. Multiple causes may lead to a variation in the perception of vibrations over time: from an increase in the train load to the roughness of the railway track, from the increase of the train speed to the modification of the dynamic response of the surrounding soil. In the present study, special attention is devoted to the effect of the hydrological regime on the latter. Two scenarios were calibrated on the results of repeated geodynamic tests on the same site in Milano but at two different times. The two investigations revealed differences in the dynamic response of above-ground soils which can be related to different saturation profiles. The passage of a typical convoy is simulated in the time domain. Differences between the two scenarios are highlighted together with the role played by the static axle load of the train. Furthermore, comparisons with recorded accelerations are provided to validate the model

A numerical assessment of variable saturation of the upper layers on the ground borne vibrations from underground trains: A case history

Ground borne vibrations generated by the passage of underground trains may change over time due to objective causes, such as increasing weight and speed of trains or ageing of the infrastructure components, as well as a variation in the dynamic response of the soil surrounding the tunnel. Among the possible causes of changes in the soil dynamic response, its hydrologic state has been seldom investigated. In this contribution, the role played by the conditions of the soil above the water table is addressed, starting from a case history in the city of Milano. Two-dimensional plane strain numerical models have been developed for the infrastructure. The models were calibrated on the results of two geophysical investigations performed at the same site in the city centre, but at two different times, which allowed distinguishing different dynamic responses. The system was excited by a synthetic load time history, matching a reference dynamic load spectrum included in Italian recommendations. Limitations of using this input on a 2D plane strain model were assessed by comparing the computed vibrations with experimental acceleration records collected on the tunnel. The results of the two numerical models are compared with those of a simulation performed assuming fully dry conditions above the water table. Overall, the set of analyses shows that even small changes in the dynamic response of the soil, interpretated as a consequence of variable saturation, may result in a change of a few decibels in the acceleration levels. Much larger accelerations are predicted on average with the simpler dry model, clearly showing the advantages of a more accurate modelling strategy