Patient and Patient Group Engagement in Cancer Clinical Trials: A Stakeholder Charter.

Background-to guide the implementation of patient centricity and engagement in cancer clinical trials (CTs) and to operationalize the Canadianized version of the Clinical Trials Transformation Initiative (C-CTTI) model, the development of a charter was identified by cancer CT stakeholders. Methods-the Canadian Cancer Trial Stakeholder Charter (the Charter) was initiated by Colorectal Cancer Canada (CCC) and developed via the-1-formation of an inclusive working group (WG) that drafted the document using recommendations collected during the development of the C-CTTI model; 2-socialization of the draft Charter to solicit feedback from cancer CT stakeholders, including those who attended the 2019 CCC Conference; and 3-incorporation of stakeholders' feedback and finalization of the Charter by the WG. Results-the Charter was built around five guiding principles-1-patient centricity; 2-commitment to education and training; 3-collaboration as equal and independent partners in research; 4-transparency and accountability; and 5-high standards in data collection integrity and honesty. These principles led to the Charter's five tenets, which stipulate stakeholder commitments, aiming to make CTs accessible to all patients, improve the design and implementation of CTs to benefit patients, expand recruitment and retention of patients in CTs, and further advance cancer research and treatment. Conclusions-the Charter is intended to integrate the patient voice into the Canadian cancer CT continuum. The next phases of the C-CTTI model include the adoption and implementation of the Charter, the establishment of a patient group training program, and the development of real-world evidence/real-world data methodologies.

Bioremediation of tetrachloroethylene-contaminated groundwater in a model aquifer: effects on green frogs (Rana clamitans) and Xenopus laevis as potential wetland receptors.

Recent regulations require that the ecological effects of microorganisms introduced into the environment, such as for groundwater bioremediation, be assessed prior to their utilization. A native anuran (Rana clamitans) and a model anuran (Xenopus laevis) were used as potential wetland receptors of tetrachloroethylene (PCE)-contaminated groundwater, undergoing three bioremediation treatments: natural attenuation (NA), biostimulation (ST), and bioaugmentation (AU). Eggs of both species were exposed acutely (96 h) to remediated effluents. Xenopus tadpoles were chronically exposed to the effluents for 100 days and were screened for the presence of bacterial pathogens. There was no impact on the survivorship of the frogs exposed either acutely or chronically to the NA, ST, or AU effluents; nor was there any evidence of bacterial infection found, with the exception of control individuals. The results of these exposures suggest that bioremediation with KB-1trade mark culture poses a minimal threat to anuran development and survivorship.

The effect of a biofilm on solute diffusion in fractured porous media.

At sites in fractured rock where contamination has been exposed to the rock matrix for extended periods of time, the amount of contaminant mass residing in the matrix can be considerable. Even though it may be possible to diminish concentrations by the advection of clean water through the fracture features, back diffusion from mass held in the matrix will lead to a continuing source of contamination. In such an event, the development of a biofilm (a thin film of microbial mass) on the wall of the fractures may act to limit or prevent the back diffusion process. The objective of this preliminary study is to explore the influence imparted by the presence of a biofilm on the process of matrix diffusion. The investigation was conducted using radial diffusion cells constructed from rock core in which biofilm growth was stimulated in a central reservoir. Once biofilms were developed, forward diffusion experiments were conducted in which a conservative solute migrated from the central reservoir into the intact rock sample. Diffusion experiments were performed in a total of 11 diffusion cell pairs where biofilm growth was stimulated in one member of the pair and inhibited in the other. The effect of the presence of a biofilm on tracer diffusion was determined by comparison of the diffusion curves produced by each cell pair. A semi-analytical model that accounts for the presence of a biofilm was used to investigate the effect of the biofilm on mass transfer due to changes in the effective porosity, effective diffusion coefficient, and the depth of penetration of the biofilm into the intact rock. The results show that the biofilm acted to plug the rock matrix, rather than forming a discrete layer on the reservoir surface. The reduction in effective porosity due to the biofilm ranged from 6% to 52% with the majority of the samples in the 30% to 50% range. Based on the present results, with more efficient biofilm stimulation, it is reasonable to assume that a more complete plugging of the microcrack porosity might be possible, leaving a much thicker and efficient barrier than could be achieved via a surface biofilm.

Long-term persistence of a nutrient-starved biofilm in a limestone fracture.

The persistence of biofilms is a key element of the biobarrier concept applied to fractured rock. After a 43-day biostimulation with molasses for the biofilm growth (phase I), the effects of a 179-day starvation on the persistence of the biofilm (phase II) were investigated in a single-fractured limestone apparatus equipped to detect small changes in hydraulic conductivity (K) (cm min(-1)). The K in the central fracture section (Kf) decreased by 4.6 logs between days 0 and 167 and increased by 1.3 logs between days 167 and 222, leading to an overall 3.3-logs reduction for the 222-day experiment. Accumulation of rod- and filamentous-shaped bacteria and deposition of minerals were thought to account for the decrease in Kf. Even though the filamentous bacterial cells possibly enhanced the stability of the developing biofilm, increases in Kf became more frequent after 100 days of operation. This decrease in stability was presumably related to sloughing events, which were in turn attributed to a combination of processes, including nutrient deprivation, the release of deposited minerals, decreasing fluid flowrate, and endogenous decay as part of biofilm ageing. This study indicates that biofilms developed in fractures can persist for extended periods at reduced K when exposed to a long-term starvation.

Measurements of groundwater velocity in discrete rock fractures.

Estimating groundwater velocity in fracture networks using a Darcy or cubic law calculation is complicated by the wide distribution of fracture aperture often found in these systems and by the difficulty in measuring hydraulic head in discrete fracture features. Although difficult to conduct in a fractured rock setting, the point dilution method can be utilized to collect direct measurements of groundwater velocity in individual fractures. To compare measured against calculated velocities, more than 100 point dilution experiments were conducted within a 35 x 35 m area of a single fracture and in discrete fracture features within a fracture network at a larger scale. The dilution experiments were conducted by isolating a fracture feature in a borehole, measuring the hydraulic aperture, and measuring the decay of an injected tracer due to the advective groundwater flux across the fracture. Groundwater velocity was estimated using the hydraulic aperture and the rate of decay of the injected tracer. Estimates of the local hydraulic gradient were calculated via the cubic law using the velocity estimate and the hydraulic aperture. The results of the tests conducted in the single fracture show variable (1 to 33 m/day) but on average higher velocities in comparison to that measured during a natural gradient tracer experiment conducted previously (in which the effects of matrix diffusion were accounted for) and to that which would be calculated using the cubic law. Based on these results, it was determined that the best estimate of the average groundwater velocity, at the scale of the measurement area used for the cubic law calculations, could only be obtained using the largest apertures in the aperture distribution. Variability of the velocity measurements was also observed over time. Increases in velocity were attributed to the effect of rainfall although concurrent increases in hydraulic gradient were not detected (likely within the tolerance of the measuring devices). The groundwater velocities measured in the fracture network varied over a wider range than at the scale of the single fracture (from 2 to 388 m/day). No correlation, however, was observed between the size of the fracture aperture and measured velocity.