In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015

Development and characterisation of a large diameter decellularised vascular allograft

The aims of this study were to develop a biological large diameter vascular graft by decellularisation of native human aorta to remove the immunogenic cells whilst retaining the essential biomechanical, and biochemical properties for the ultimate benefit of patients with infected synthetic grafts. Donor aortas (n = 6) were subjected to an adaptation of a propriety decellularisation process to remove the cells and acellularity assessed by histological analysis and extraction and quantification of total DNA. The biocompatibility of the acellular aortas was determined using standard contact cytotoxicity tests. Collagen and denatured collagen content of aortas was determined and immunohistochemistry was used to determine the presence of specific extracellular matrix proteins. Donor aortas (n = 6) were divided into two, with one half subject to decellularisation and the other half retained as native tissue. The native and decellularised aorta sections were then subject to uniaxial tensile testing to failure [axial and circumferential directions] and suture retention testing. The data was compared using a paired t-test. Histological evaluation showed an absence of cells in the treated aortas and retention of histoarchitecture including elastin content. The decellularised aortas had less than 15 ng mg¯¹ total DNA per dry weight (mean 94% reduction) and were biocompatible as determined by in vitro contact cytotoxicity tests. There were no gross changes in the histoarchitecture [elastin and collagen matrix] of the acellular aortas compared to native controls. The decellularisation process also reduced calcium deposits within the tissue. The uniaxial tensile and suture retention testing revealed no significant differences in the material properties (p > 0.05) of decellularised aorta. The decellularisation procedure resulted in minimal changes to the biological and biomechanical properties of the donor aortas. Acellular donor aorta has excellent potential for use as a large diameter vascular graft

Oral manifestations of thrombocytopaenia

The appearance in the mouth of haemorrhagic petechiae, ecchymoses or blood blisters with spontaneous bleeding is suggestive of a haemorrhagic disorder that may be caused either by functional impairment of platelets or of blood vessel walls, by an abnormal decrease in the number of circulating platelets (thrombocytopaenia), or by defects in the blood clotting mechanism. Thrombocytopaenia from decreased production or increased destruction of platelets may be caused by multiple factors including immune mediated mechanisms, drugs or infections. A diagnosis of thrombocytopaenic purpura can be made when any other disease entity that might be causing the purpura is excluded on the basis of the medical history, the physical examination, a complete blood count and a peripheral blood smear. In this paper, we outline the clinical features of oral thrombocytopaenic purpura and briefly discuss some aspects of its aetiopathogenesis and treatment

Microstructure and Fabric Transitions in Calcite Tectonites from the Sierra Alhamilla

A suite of marble specimens from the Sierra Alhamilla (Spain), deformed to large strains under natural conditions at about 300° C shows distinct variations in microstructure and fabrics. It can be demonstrated that the development of crystallographic preferred orientations and grain shape fabrics are strongly dependent on recrystallized grain size. This is interpreted to reflect the relative importance of various deformational mechanisms. Superplasticity seems to have a sharp upper grain size limit at 10–15 /smm. Within the power law creep regime, deformation in fine grained aggregates is probably dominated by diffusional, in coarser ones by dislocation mechanisms. The transition is a gradual one, and may span a grain size range of 30 /sm

Experimental investigation into the sealing capability of naturally fractured shale caprocks to supercritical carbon dioxide flow

Geological storage of CO is considered a solution for reducing the excess CO released into the atmosphere. Low permeability caprocks physically trap CO injected into underlying porous reservoirs. Injection leads to increasing pore pressure and reduced effective stress, increasing the likelihood of exceeding the capillary entry pressure of the caprocks and of caprock fracturing. Assessing on how the different phases of CO flow through caprock matrix and fractures is important for assessing CO storage security. Fractures are considered to represent preferential flow paths in the caprock for the escape of CO. Here we present a new experimental rig which allows 38 mm diameter fractured caprock samples recovered from depths of up to 4 km to be exposed to supercritical CO (scCO) under in situ conditions of pressure, temperature and geochemistry. In contrast to expectations, the results indicate that scCO will not flow through tight natural caprock fractures, even with a differential pressure across the fractured sample in excess of 51 MPa. However, below the critical point where CO enters its gas phase, the CO flows readily through the caprock fractures. This indicates the possibility of a critical threshold of fracture aperture size which controls CO flow along the fracture

Shear behavior of DFDP-1 borehole samples from the Alpine Fault, New Zealand, under a wide range of experimental conditions

The Alpine Fault is a major plate-boundary fault zone that poses a major seismic hazard in southern New Zealand. The initial stage of the Deep Fault Drilling Project has provided sample material from the major lithological constituents of the Alpine Fault from two pilot boreholes. We use laboratory shearing experiments to show that the friction coefficient µ of fault-related rocks and their precursors varies between 0.38 and 0.80 depending on the lithology, presence of pore fluid, effective normal stress, and temperature. Under conditions appropriate for several kilometers depth on the Alpine Fault (100 MPa, 160 °C, fluid-saturated), a gouge sample located very near to the principal slip zone exhibits µ = 0.67, which is high compared with other major fault zones targeted by scientific drilling, and suggests the capacity for large shear stresses at depth. A consistent observation is that every major lithological unit tested exhibits positive and negative values of friction velocity dependence. Critical nucleation patch lengths estimated using representative values of the friction velocity-dependent parameter a−b and the critical slip distance D c , combined with previously documented elastic properties of the wall rock, may be as low as ~3 m. This small value, consistent with a seismic moment M o = ~4 × 1010 for an M w = ~1 earthquake, suggests that events of this size or larger are expected to occur as ordinary earthquakes and that slow or transient slip events are unlikely in the approximate depth range of 3–7 km

New Experimental Equipment Recreating Geo-Reservoir Conditions in Large, Fractured, Porous Samples to Investigate Coupled Thermal, Hydraulic and Polyaxial Stress Processes

Abstract Use of the subsurface for energy resources (enhanced geothermal systems, conventional and unconventional hydrocarbons), or for storage of waste (CO2, radioactive), requires the prediction of how fluids and the fractured porous rock mass interact. The GREAT cell (Geo-Reservoir Experimental Analogue Technology) is designed to recreate subsurface conditions in the laboratory to a depth of 3.5 km on 200 mm diameter rock samples containing fracture networks, thereby enabling these predictions to be validated. The cell represents an important new development in experimental technology, uniquely creating a truly polyaxial rotatable stress field, facilitating fluid flow through samples, and employing state of the art fibre optic strain sensing, capable of thousands of detailed measurements per hour. The cell’s mechanical and hydraulic operation is demonstrated by applying multiple continuous orientations of principal stress to a homogeneous benchmark sample, and to a fractured sample with a dipole borehole fluid fracture flow experiment, with backpressure. Sample strain for multiple stress orientations is compared to numerical simulations validating the operation of the cell. Fracture permeability as a function of the direction and magnitude of the stress field is presented. Such experiments were not possible to date using current state of the art geotechnical equipment