Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patients candidated to autologous hematopoietic stem cell transplantation

We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay ( BFU- E and CFU- GM) in short- term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL- 6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients ( 68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU- E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL- 6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/ or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting

A review of the approaches to predict the ease of swallowing and post-swallow residues

Background Swallowing is a complex physiological process transporting food from the mouth into the esophagus. Understanding how food properties condition flow, ease of swallowing and amount of post-swallow residues can support the design and development of novel products with improved texture and swallow-ability. Diagnostics allowed visualizing directly the effect of bolus consistency on flow, but complementary approaches are needed to speed up the pace of product innovation. Scope and approach This review summarizes the state of the art with respect to the in vitro and in silico approaches to predict the ease of swallowing, with an overview of the oral, pharyngeal and esophageal swallowing. Physical and computational models are discussed and compared, highlighting capabilities and limitations. Key findings and conclusions In vitro and in silico experiments represent attractive complements to the in vivo investigations because they allow varying parameters independently, which is key to understand the effect of different food and drink properties and to adapting them to different needs. Two motor control strategies are commonly used, namely imposing displacements or stresses. These models have helped clarifying the role of bolus rheology in the oral phase of swallowing and the importance of salivary coating in the pharyngeal bolus flow. Few areas of improvements were identified: the use of more realistic geometries and mechanical properties representing the relevant tissues, of lubrication boundary conditions and of a wider variety of food boli. Further clinical studies should also focus on identifying the most realistic motor control strategy to mimic human swallowing.</p

Reprint of "Experiments and discrete element simulation of the dosing of cohesive powders in a simplified geometry"

(Reprinted from Powder Technoly, vol 287, pg 108-120

Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patients candidated to autologous hematopoietic stem cell transplantation

We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay ( BFU- E and CFU- GM) in short- term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL- 6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients ( 68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU- E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL- 6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/ or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting

Slow stress relaxation behavior of cohesive powders

We present uniaxial (oedometric) compression tests on two cohesive industrially relevant granular materials (cocoa and limestone powder). A comprehensive set of experiments is performed using two devices – the FT4 Powder Rheometer and the custom made lambdameter – in order to investigate the dependence of the powders' behavior on the measurement cell geometries, stress level, relaxation time and applied strain rate. The aspect ratio α, tested with the FT4, is found to play no role for vessels with α ≲ 1 while material characteristics strongly affect the stress–strain response. After compression is stopped, the constant volume stress relaxation is found to follow a power law, consistently for both cohesive powders and for the different testing equipments. A simple (incremental, algebraic) stress evolution model is proposed to describe the relaxation of cohesive powders, which includes a response timescale along with a second, dimensionless relaxation parameter that sets the very small power law, i.e. extremely slow stress relaxation

Characterisation of cohesive powders for bulk handling and dem modelling

The flow behaviour of granular materials is relevant for many industrial applications including the pharmaceutical, chemical, consumer goods and food industries. A key issue is the accurate characterisation of these powders under different loading conditions and flow regimes, for example in mixers, pneumatic conveyors and silo filling and discharge. This paper explores the experimental aspects of cohesive powder handling at different compaction levels and flow regimes, namely inertial and quasi-static regimes. So far, laboratory element test set-ups capable of defining the full stress states at very low compaction levels have not been fully explored in literature. In contrast the mechanical behaviour of cohesive powders under relatively high consolidation stress (several kPa upward) can be carefully measured using element tests such as biaxial test, true triaxial and hollow cylinder tests. However in practice these tests are expensive and slow to conduct and are almost never performed for many industrial applications requiring material characterisation. Here we investigate simpler techniques that could be used for filling this important gap with the focus of providing test data for model calibration and simulation validation in line with the spirit of the European Commission funded PARDEM Marie Curie ITN Project. We perform particle and bulk characterisation on limestone powder with 4.7μm and 31.3 μm mean particle size, detergent powder with differences in formulation, cocoa powder with low and high fat content - relevant for different industrial applications. Of particular significance is the 4.7μm limestone powder which is the PARDEM reference powder that have been created and extensively used in a collaborative European PARDEM Project (www.pardem.eu). In the inertial, low consolidation stress regimes - more relevant for powder transport and conveying applications - we present experimental findings on the flowability and avalanching behaviour of the reference material in a rotating drum. On the other hand, in the quasi-static, higher consolidation regime, we perform shear tests with the Edinburgh Powder Tester (EPT), an extended uniaxial tester and the commercially available Freeman FT4 Powder Rheometer. For macroscopic quantities, we report the unconfined yield strength as a function of applied stress. These material characteristics provide important scientific insights for developing innovative solutions for cohesive powder handling problems. From these experiments and for best practice guideline, we highlight subtle issues associated with the experimental setup and measurements. The experiments lead to a rich quantitative description of the flow behaviour and failure properties of the materials which provide the material data for DEM model calibration and validation