Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report

Background Primary myelofibrosis is a myeloproliferative disorder characterized by bone marrow fibrosis, abnormal cytokine expression, splenomegaly and anemia. The activation of JAK2 and the increased levels of circulating proinflammatory cytokines seem to play an important role in the pathogenesis of myelofibrosis. Novel therapeutic agents targeting JAKs have been developed for the treatment of myeloproliferative disorders. Ruxolitinib (INCB018424) is the most recent among them. Case presentation To our knowledge, there is no evidence from clinical trials of an increased risk of tuberculosis during treatment with JAK inhibitors. Here we describe the first case of tuberculosis in a patient treated with Ruxolitinib, a male with a 12-year history of chronic idiopathic myelofibrosis admitted to our Institute because of fever, night sweats, weight loss and an enlarging mass in the left inguinal area for two months. Conclusion Treatment with Ruxolitinib may have triggered the reactivation of latent tuberculosis because of an inhibition of Th1 response. Our case highlights the importance of an accurate screening for latent tuberculosis before starting an anti-JAK 2 treatmen

Tests of varied sample preparation methods for centrifuge modelling

Centrifuge modelling is an established technique capable of investigating the ground’s response to complex geotechnical events. Centrifuge models are often created from reconstituted soil, with well-defined boundary conditions and known soil parameters. Clay soil models may be prepared by mixing clay powder with distilled water to form a slurry. This slurry is placed within a soil container and subjected to a vertical stress (usually in a consolidation press or consolidated inflight). This creates an isotropic model but there is a fundamental difference between this soil model and naturally occurring soil deposits. The structure and fabric present within a naturally occurring clay is not reproduced by this preparation process. It is well-established that structure and fabric in naturally deposited soils are as significant in their effect on soil behaviour as, for instance, the stress history. Inherent structure and fabric within clay soils creates anisotropy which can vary with depth, this is particularly apparent when considering the permeability. Creating a soil model for centrifuge modelling with representative permeability anisotropy would allow for a better representation of consolidation driven events and the ability to observe long-term behaviour of complex geotechnical events. Currently, there are limited methods of doing so, leading to a considerable gap in knowledge associated with the behaviour of layered ground. This paper describes the development of the equipment and experimental procedure for quantifying the structure developed by different sample preparation techniques for centrifuge modelling

A numerical model to study the response of piles under lateral loading in unsaturated soils

The interaction between a laterally loaded pile and the surrounding soil is typically limited to the shallower soil layer. Often, this zone is above the water table and therefore the interaction takes place under unsaturated conditions. The available evidence is scarce but suggests that unsaturated conditions play a major role on the pile’s response. The actual mechanisms governing the soil–pile interaction under unsaturated soil conditions are not understood entirely, and this paper provides a useful insight on this topic. The analysis is carried out with a fully coupled three-dimensional numerical model, the soil behaviour is simulated with a Modified Cam Clay Model extended to unsaturated conditions. The model accounts for the increase in stiffness and strength of unsaturated soils as well as the volumetric collapse upon wetting. The constitutive model is calibrated on the laboratory data and validated against centrifuge data with satisfying agreement. The results highlight the substantial differences in the soil reaction against the pile depending on different water saturation profiles. The study also shows that the influence of unsaturated conditions on the pile response increases as the pile’s flexibility increases. Comparing the findings with currently available design methods such as the p-y curves, it is found that these do not adequately describe the unsaturated soil reaction against the pile, which opens the door for new research in the field. The proposed numerical model is a promising tool to further investigate the mechanisms underlying the soil–pile interaction under unsaturated soils

Numerical modelling of the response of an unsaturated silty soil under wetting and gravitational loading processes

This paper presents the results of a numerical study aiming at simulating the response of an unsaturated fine-grained soil under wetting and gravitational loading processes. This study is based on the results of some centrifuge tests carried out to assess the influence of partial saturation on the laterally loaded pile response. The hydro-mechanical behaviour of the silty soil is described using a constitutive model adapted to unsaturated conditions. The model predictions are compared with the measurements provided by LVDTs and laser transducers in the first phases of the experimental study. Besides validating the model, the numerical study aimed at investigating the influence of the after-compaction conditions on both the displacement field and the evolution of the more significant state variables during imbibition and gravitational loading processes. Finally, an additional analysis is conducted to determine the effects of the pile installation on the soil response

Centrifuge Modelling of Long-term Tunnelling Ground Movements

The increasing demand for public transport provision in cities has resulted in a requirement for enlarged public transport infrastructure. Where underground railways represent an important component of these systems, tunnel construction will inevitably lead to some degree of ground movement that can cause damage to surface structures and buried structures and services. It is important, therefore, that in the design of tunnels in urban environments these ground movements are predicted reliably. Predicting short-term ground movements resulting from tunnelling is standard when assessing the potential for damage to adjacent infrastructure. However, long-term tunnelling-induced ground movements and how these develop are understood less well and a research programme, based on geotechnical centrifuge modelling, is being conducted to improve our fundamental scientific understanding of this. The first stage of the programme has been to develop an apparatus that simulates the construction of a tunnel with a lining of known stiffness and permeability and allows construction ground loss to be replicated correctly. This paper describes the initial development of the apparatus along with results and analysis that demonstrates the suitability of the technique for the proposed study. The results obtained were observed to represent the short-term settlements that might be expected above a tunnel excavated in clay. The results also prove the modelling technique suitable for application in a full parametric study in which the geometry and boundary conditions of the model will be varied together with the permeability of the tunnel liner

Experimental technique for creating enhanced capacity piles in a centrifuge environment

none3The paper describes experimental techniques developed in the geotechnical centrifuge facility at City, University of London to test bored pile foundations with profiled bores designed to increase pile capacity. Improvements were made to existing equipment to ensure accurate measurement of the load displacement response at working loads and potential errors quantified.openLeonardo Maria Lalicata, Andrew McNamara, Sarah Elizabeth StallebrassLalicata, LEONARDO MARIA; Mcnamara, Andrew; Elizabeth Stallebrass, Sara

An experimental study into the ultimate capacity of an 'impression' pile in clay

The ultimate capacity of a novel type of piled foundation called an 'impression' pile has been investigated using centrifuge modelling techniques. The name derives from the small discrete impressions created in the side walls of a bored cast in situ pile to increase the soil/pile friction such that the impressions form nodules on the shaft of the concreted pile. The technology is suitable for bored piles in overconsolidated clay, such as London Clay. The experiments explored the influence of geometrical parameters such as the vertical spacing of the impressions, their number at each level and their shape. The data show a consistent increase in pile capacity of 40% when the impressions extend over 85% of the pile length. The ultimate capacity of the pile is primarily affected by the length of the pile which is impressed, the number of nodules at a given cross-section and the spacing of the nodules in the vertical direction, as long as this is greater than a threshold value. According to the experimental evidence, a block failure occurs for a spacing lower than this threshold value. Plastic failure mechanisms for the impression pile were established. These were used successfully to calculate the ultimate capacity of the impression piles tested with an error of less than 10%

Laterally loaded pile in unsaturated soils, a numerical study

none4The influence of partial saturation on laterally loaded piles response has been studied perform-ing three-dimensional simulation using a finite element code. The analysis simulated a single vertical floating pile embedded in a normally consolidated silty clay, subjected to a static horizontal force applied at pile head. The study aims at exploring the influence of the relative position of water table with respect to the pile length. The hydro-mechanical propriety of soil is kept constant. The constitutive model adopted to simulate the soil stress-strain response is an extension of modified Cam-Clay model that considers the evolution of the yielding surface due to variation of saturation degree. The model is formulated in terms of modified Bishop effective stress, which allows switching continuously from saturated conditions to unsaturated conditions and vice ver-sa. The modified formulation of the hardening parameter allows to correctly reproduce the volumetric behaviour observed in wetting and drying path.mixedL. M. Lalicata; A. Desideri; F. Casini; L. ThorelLalicata, L. M.; Desideri, A.; Casini, F.; Thorel, L