In dealing with systems as complex as the cytoskeleton, we need organizing principles or, short of that, an empirical framework into which these systems fit. We report here unexpected invariants of cytoskeletal behavior that comprise such an empirical framework. We measured elastic and frictional moduli of a variety of cell types over a wide range of time scales and using a variety of biological interventions. In all instances elastic stresses dominated at frequencies below 300 Hz, increased only weakly with frequency, and followed a power law; no characteristic time scale was evident. Frictional stresses paralleled the elastic behavior at frequencies below 10 Hz but approached a Newtonian viscous behavior at higher frequencies. Surprisingly, all data could be collapsed onto master curves, the existence of which implies that elastic and frictional stresses share a common underlying mechanism. Taken together, these findings define an unanticipated integrative framework for studying protein interactions within the complex microenvironment of the cell body, and appear to set limits on what can be predicted about integrated mechanical behavior of the matrix based solely on cytoskeletal constituents considered in isolation. Moreover, these observations are consistent with the hypothesis that the cytoskeleton of the living cell behaves as a soft glassy material, wherein cytoskeletal proteins modulate cell mechanical properties mainly by changing an effective temperature of the cytoskeletal matrix. If so, then the effective temperature becomes an easily quantified determinant of the ability of the cytoskeleton to deform, flow, and reorganize.

A B S T R A C T PurposeNational guidelines recommend that discussions about end-of-life (EOL) care planning happen early for patients with incurable cancer. We do not know whether earlier EOL discussions lead to less aggressive care near death. We sought to evaluate the extent to which EOL discussion characteristics, such as timing, involved providers, and location, are associated with the aggressiveness of care received near death. Patients and MethodsWe studied 1,231 patients with stage IV lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium, a population-and health system-based prospective cohort study, who died during the 15-month study period but survived at least 1 month. Our main outcome measure was the aggressiveness of EOL care received. ResultsNearly half of patients received at least one marker of aggressive EOL care, including chemotherapy in the last 14 days of life (16%), intensive care unit care in the last 30 days of life (9%), and acute hospital-based care in the last 30 days of life (40%). Patients who had EOL discussions with their physicians before the last 30 days of life were less likely to receive aggressive measures at EOL, including chemotherapy (P ϭ .003), acute care (P Ͻ .001), or any aggressive care (P Ͻ .001). Such patients were also more likely to receive hospice care (P Ͻ .001) and to have hospice initiated earlier (P Ͻ .001). ConclusionEarly EOL discussions are prospectively associated with less aggressive care and greater use of hospice at EOL.

Background National guidelines recommend that physicians discuss end-of-life (EOL) care planning with cancer patients whose life expectancy is less than one year. Objective To evaluate the incidence of EOL discussions for patients with stage IV lung or colorectal cancer, and where, when, and with whom discussions take place. Design Prospective cohort study of patients diagnosed with lung or colorectal cancer from 2003 to 2005. Setting Subjects lived in Northern California, Los Angeles County, North Carolina, Iowa, or Alabama, or received care in one of five large health maintenance organizations or one of fifteen Veteran’s Health Administration sites. Patients 2155 patients with stage IV lung or colorectal cancer. Measurements EOL discussions reported in patient and surrogate interviews or documented in medical records through 15 months after diagnosis. Results 73% of patients had EOL discussions identified by at least one source. Among patients who died during follow-up (N=1470), 87% had EOL discussions, versus 41% of patients who were alive at the end of follow-up (N=685). Among first EOL discussions documented in records (N=1081), 55% occurred in the hospital. Oncologists documented EOL discussions with only 27% of their patients. Among patients with documented EOL discussions who died during follow-up (N=959), discussions took place a median of 33 days before death. Limitations The depth and quality of EOL discussions was not evaluated. Much of the information about discussions came from surrogates of patients who died before baseline interviews could be obtained. Conclusions Although most patients with stage IV lung or colorectal cancer have discussions with physicians about EOL care planning before death, many discussions occur during acute hospital care, with non-oncology providers, and late in the course of illness.