Predictive oncology: a review of multidisciplinary, multiscale in silico modeling linking phenotype, morphology and growth.

Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable understanding of the connections between phenotype and tumor morphology. Here, we critically assess advantages and disadvantages of recent computational modeling efforts (e.g., continuum, discrete, and cellular automata models) that have pursued this understanding. Based on this assessment, we review a multiscale, i.e., from the molecular to the gross tumor scale, mathematical and computational "first-principle" approach based on mass conservation and other physical laws, such as employed in reaction-diffusion systems. Model variables describe known characteristics of tumor behavior, and parameters and functional relationships across scales are informed from in vitro, in vivo and ex vivo biology. We review the feasibility of this methodology that, once coupled to tumor imaging and tumor biopsy or cell culture data, should enable prediction of tumor growth and therapy outcome through quantification of the relation between the underlying dynamics and morphological characteristics. In particular, morphologic stability analysis of this mathematical model reveals that tumor cell patterning at the tumor-host interface is regulated by cell proliferation, adhesion and other phenotypic characteristics: histopathology information of tumor boundary can be inputted to the mathematical model and used as a phenotype-diagnostic tool to predict collective and individual tumor cell invasion of surrounding tissue. This approach further provides a means to deterministically test effects of novel and hypothetical therapy strategies on tumor behavior.

Subnanometer-resolution structures of the grass carp reovirus core and virion.

Grass carp reovirus (GCRV) is a member of the Aquareovirus genus of the family Reoviridae, a large family of double-stranded RNA (dsRNA) viruses infecting plants, insects, fishes and mammals. We report the first subnanometer-resolution three-dimensional structures of both GCRV core and virion by cryoelectron microscopy. These structures have allowed the delineation of interactions among the over 1000 molecules in this enormous macromolecular machine and a detailed comparison with other dsRNA viruses at the secondary-structure level. The GCRV core structure shows that the inner proteins have strong structural similarities with those of orthoreoviruses even at the level of secondary-structure elements, indicating that the structures involved in viral dsRNA interaction and transcription are highly conserved. In contrast, the level of similarity in structures decreases in the proteins situated in the outer layers of the virion. The proteins involved in host recognition and attachment exhibit the least similarities to other members of Reoviridae. Furthermore, in GCRV, the RNA-translocating turrets are in an open state and lack a counterpart for the sigma1 protein situated on top of the close turrets observed in mammalian orthoreovirus. Interestingly, the distribution and the organization of GCRV core proteins resemble those of the cytoplasmic polyhedrosis virus, a cypovirus and the structurally simplest member of the Reoviridae family. Our results suggest that GCRV occupies a unique structure niche between the simpler cypoviruses and the considerably more complex mammalian orthoreovirus, thus providing an important model for understanding the structural and functional conservation and diversity of this enormous family of dsRNA viruses.

Environmental sustainability and the human element: Decision making in National Cancer Institute-designated cancer centers and Practice Greenhealth subscribing institutions

Background. Various aspects of sustainability have taken root in the hospital environment; however, decisions to pursue sustainable practices within the framework of a master plan are not fully developed in National Cancer Institute (NCI) -designated cancer centers and subscribing institutions to the Practice Greenhealth (PGH) listserv.^ Methods. This cross sectional study was designed to identify the organizational characteristics each study group pursed to implement sustainability practices, describe the barriers they encountered and reasons behind their choices for undertaking certain sustainability practices. A web-based questionnaire was pilot tested, and then sent out to 64 NCI-designated cancer centers and 1638 subscribing institutions to the PGH listserv.^ Results. Complete responses were received from 39 NCI-designated cancer centers and 58 subscribing institutions to the PGH listserv. NCI-designated cancer centers reported greater progress in integrating sustainability criteria into design and construction projects than hospitals of institutions subscribing to the PHG listserv (p-value = <0.05). Statistically significant differences were also identified between these two study groups in undertaking work life options, conducting energy usage assessments, developing energy conservation and optimization plans, implementing solid waste and hazardous waste minimization programs, using energy efficient vehicles and reporting sustainability progress to external stakeholders. NCI-designated cancer centers were further along in implementing these programs (p-value = <0.05). In comparing the self-identified NCI-designated cancer centers to centers that indicated they were both and NCI and PGH, the later had made greater progress in using their collective buying power to pursue sustainable purchasing practices within the medical community (p-value = <0.05). In both study groups, recycling programs were well developed.^ Conclusions. Employee involvement was viewed as the most important reason for both study groups to pursue recycling initiatives and incorporated environmental criteria into purchasing decisions. A written sustainability commitment did not readily translate into a high percentage that had developed a sustainability master plan. Coordination of sustainability programs through a designated sustainability professional was not being undertaken by a large number of institutions within each study group. This may be due to the current economic downturn or management's attention to the emerging health care legislation being debated in congress. ^ Lifecycle assessments, an element of a carbon footprint, are seen as emerging areas of opportunity for health care institutions that can be used to evaluate the total lifecycle costs of products and services.^