Intratumor cellular heterogeneity and non-genetic cell plasticity in tumors pose a recently recognized challenge to cancer treatment. Because of the dispersion of initial cell states within a clonal tumor cell population, a perturbation imparted by a cytocidal drug only kills a fraction of cells. Due to dynamic instability of cellular states the cells not killed are pushed by the treatment into a variety of functional states, including a “stem-like state” that confers resistance to treatment and regenerative capacity. This immanent stress-induced stemness competes against cell death in response to the same perturbation and may explain the near-inevitable recurrence after any treatment. This double-edged-sword mechanism of treatment complements the selection of preexisting resistant cells in explaining post-treatment progression. Unlike selection, the induction of a resistant state has not been systematically analyzed as an immanent cause of relapse. Here, we present a generic elementary model and analytical examination of this intrinsic limitation to therapy. We show how the relative proclivity towards cell death versus transition into a stem-like state, as a function of drug dose, establishes either a window of opportunity for containing tumors or the inevitability of progression following therapy. The model considers measurable cell behaviors independent of specific molecular pathways and provides a new theoretical framework for optimizing therapy dosing and scheduling as cancer treatment paradigms move from “maximal tolerated dose,” which may promote therapy induced-stemness, to repeated “minimally effective doses” (as in adaptive therapies), which contain the tumor and avoid therapy-induced progression.
Attention-Deficit/Hyperactivity Disorder impacts children’s participation in activities that require attention to instruction, sustained mental effort, and executive functioning. Physical activity has been correlated to improvement in attention in children with ADHD. Rock climbing challenges muscular endurance, attention, and route planning. Five participants, aged 8-13, participated in the climbing program. Attention was measured pre and post climbing intervention with Trail Making Test B (TMT-B) for time to complete. Exercise intensity was measured by heart rate. Parent feedback on behavior was collected with the Conner’s Parent Rating Scale (CPRS). The social validity of the intervention was measured by the IRP-15 measures. Statistically, significant intrasession attention improvements were noted in all 5 climbers (p=.43). Two climbers were consistently working at a moderate intensity (40-60% HRmax) while 3 climbers maintained a light level of intensity (20-40% HRmax). No statistically significant improvements were found on the CPRS, although improvements are noted with qualitative reports from parents. The IRP-15 showed 100% of parents believed rock climbing was an effective intervention for their children with ADHD. Rock climbing at a light to moderate intensity is associated with improvements in attention and behavior in children with ADHD.
Provision of medication abortion in student health centers (SHC) is safe and effective, but only two states require public SHCs to provide such services. Washington state does not require medication abortion in public SHCs, yet abortion demand is greater and out-of-state patients have increased following the Dobbs decision. Here, we estimate demand for medication abortion and describe barriers to care among Washington public university students. Using publicly available data, we estimated that students at the 11 Washington public universities obtained between 404 and 549 medication abortions annually. Students must travel an average of 16 miles (range:1-78) or 73 minutes via public transit (range:22-284) round trip to the nearest abortion-providing facility. Average wait time for the first available appointment was 10 days (range:4-14), and average cost was $711. Public universities can play an integral role in expanding abortion access post-Dobbs by providing medication abortion, effectively reducing barriers to care for students.
Intratumor cellular heterogeneity and non-genetic cell plasticity in tumors pose a recently recognized challenge to cancer treatment. Because of the dispersion of initial cell states within a clonal tumor cell population, a perturbation imparted by a cytocidal drug only kills a fraction of cells. Due to dynamic instability of cellular states the cells not killed are pushed by the treatment into a variety of functional states, including a "stem-like state" that confers resistance to treatment and regenerative capacity. This immanent stress-induced stemness competes against cell death in response to the same perturbation and may explain the near-inevitable recurrence after any treatment. This double-edged-sword mechanism of treatment complements the selection of preexisting resistant cells in explaining post-treatment progression. Unlike selection, the induction of a resistant state has not been systematically analyzed as an immanent cause of relapse. Here, we present a generic elementary model and analytical examination of this intrinsic limitation to therapy. We show how the relative proclivity towards cell death versus transition into a stem-like state, as a function of drug dose, establishes either a window of opportunity for containing tumors or the inevitability of progression following therapy. The model considers measurable cell behaviors independent of specific molecular pathways and provides a new theoretical framework for optimizing therapy dosing and scheduling as cancer treatment paradigms move from "maximal tolerated dose," which may promote therapy induced-stemness, to repeated "minimally effective doses" (as in adaptive therapies), which contain the tumor and avoid therapy-induced progression.
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