Metastasis and bone loss: Advancing treatment and prevention

Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy

High-rate thermomechanical behavior of poly(vinyl chloride) and plasticized poly(vinyl chloride)

A combined experimental and analytical investigation was carried out in order to develop predictive capabilities for the rate-dependent behavior of poly(vinyl chloride) (PVC) and a dioctyl phthalate (DOP)-plasticized PVC, with focus on predicting the thermo-mechanically coupled behavior under high rates of deformation. The two materials were studied experimentally using both dynamic mechanical analysis (DMA) and compression testing over a wide range of strain rates (10$^{ - 4}$ s$^{ - 1}$ to 2000 s$^{ - 1})$. DMA testing revealed both an $\alpha$-transition and a low-temperature $\beta$-transition (-56$^{\circ}$C) in the neat PVC; the incorporation of 20wt% DOP in PVC reduced the $\alpha$-transition temperature by 54$^{\circ}$C, and also suppressed the $\beta$-transition peak. In compression testing, rate-sensitivity transitions were observed in both the neat PVC and the PVC-20wt% DOP compound. The transition in PVC is attributed to the shift of the $\beta$-transition, whereas the transition in the 20wt% DOP blend is due to the rubbery-to-glassy transition as the deformation rate goes from low to high. A constitutive model for the finite strain deformation of amorphous polymers, introduced elsewhere [1,2] and tailored here for the two material systems of interest, is shown to capture the large deformation stress-strain behavior at all rates tested

Climate change, species thermal emergence, and conservation design: a case study in the Canadian Northwest Atlantic

Marine Protected Areas (MPAs) are conservation tools that promote biodiversity by regulating human impacts. However, because MPAs are fixed in space and, by design, difficult to change, climate change may challenge their long-term effectiveness. It is therefore imperative to consider anticipated ecological changes in their design. We predict the time of emergence (ToE: year when temperatures will exceed a species’ tolerance) of 30 fish and invertebrate species in the Scotian Shelf-Bay of Fundy draft network of conservation areas based on climate projections under two contrasting emission scenarios (RCP 2.6 and RCP 8.5). We demonstrate a strong Southwest-to-Northeast gradient of change under both scenarios. Cold water-associated species had earlier ToEs, particularly in southwesterly areas. Under low emissions, 20.0% of habitat and 12.6% of species emerged from the network as a whole by 2100. Under high emissions, 51% of habitat and 42% of species emerged. These impacts are expected within the next 30–50 years in some southwestern areas. The magnitude and velocity of change will be tempered by reduced emissions. Our identification of high- and low-risk areas for species of direct and indirect conservation interest can support decisions regarding site and network design (and designation scheduling), promoting climate resilience

Combining thermoelastic and stress function to evaluate individual stresses around a near-edge hole

Individual stresses are determined on and near the edge of a hole which is located below a concentrated edge-load in an approximate half-plane. Experimental thermoelastic data are combined with an Airy’s stress function. Coefficients of the stress function are evaluated from the recorded TSA data and the traction-free conditions on the hole boundary are satisfied by imposing srr = trq = 0 on the edge of the hole for all values of the angle q. This advantageously enables one to reduce the number of coefficients in the stress function series. The method simultaneously smoothes the measured input data, satisfies the traction-free boundary conditions and evaluates individual stresses on, and in the neighborhood of, the edge of the hole

Determining individual stresses around a near-edge hole in a plate subjected to an offset load using thermoelasticity

The paper combines an Airy’s stress function in real, polar coordinates with the experimental method of thermoelastic stress analysis (TSA) to determine the individual stresses in an aluminum half-plane which contains a near-edge circular hole, the plate being subjected to a concentrated edge load away from the hole. The coefficients of the stress function are evaluated from the thermoelastically measured data using the least squares method. Imposing the traction-free conditions analytically, rather than discretely, on the edge of the hole significantly reduces the number of coefficients one must retain in the stress function, the number of equations involved in the least squares process, and in some cases the amount of measured input data needed. Problems such as the present one can also be solved from photoelastically recorded isochromatics. However, whereas the latter approach necessitates time-consuming iterative non-linear least squares, the present TSA-based scheme only requires linear least squares. TSA, which can be applied to the actual material of interest (no model or coating is needed, other than perhaps being painted flat black to enhance the uniformity and emissivity of the material) benefits from the availability of contemporary commercial systems capable of providing extensive amounts of data in a matter of minutes

Stresses at and in the neighbourhood of a near-edge hole in a plate subjected to an offset load from measured temperatures

An Airy stress function is used to process the associated temperature data and thereby determine the individual stresses in a plate containing a near-edge circular hole and which is subjected to a concentrated edge load away from the hole. Formulating the stress function so its origin is at the center of the hole enables the traction-free conditions to be imposed analytically on the edge of the hole. This significantly reduces the number of coefficients that must be retained in the stress function. Results agree with those from measured strains and the finite element method. The capability developed is applicable beyond the present situation, including with other measured quantities such as strains or displacements