Characterization of interstitial stem cells in hydra by cloning

A procedure has been developed for cloning interstitial stem cells from hydra. Clones are prepared by introducing small numbers of viable cells into aggregates of nitrogen mustard-inactivated host tissue. Clones derived from added stem cells are identified after 1–2 weeks of growth by staining with toluidine blue. The incidence of clones increases with increasing input of viable cells according to one-hit Poisson statistics, indicating that clones arise from single cells. After correction for cell losses in the procedure, about 1.2% of the input cells are found to form clones. This compares with estimates from in vivo experiments of about 4% stem cells in whole hydra [David, C. N., and Gierer, A. (1974). Cell cycle kinetics and development of Hydra attenuata. III. Nerve and nematocyte differentiation. J. Cell Sci. 16, 359–375.] Differentiation of nematocytes and nerve cells in clones was analyzed by labeling precursors with [3H]thymidine and scoring labeled nerves and nematocytes 2 days later. Nine clones examined in this way contained both differentiated nerve cells and nematocytes, demonstrating that the interstitial stem cell is multipotent. This result suggests that the observed localization of nerve and nematocyte differentiation in whole hydra probably occurs at the level of stemcell determination. The observation that differentiated cells occur very early in clone development suggests that a stem cell's decision to proliferate or differentiate is regulated by shortrange feedback signals which are already saturated in young clones

Linear mixed models with endogenous covariates: modeling sequential treatment effects with application to a mobile health study

Mobile health is a rapidly developing field in which behavioral treatments are delivered to individuals via wearables or smartphones to facilitate health-related behavior change. Micro-randomized trials (MRT) are an experimental design for developing mobile health interventions. In an MRT the treatments are randomized numerous times for each individual over course of the trial. Along with assessing treatment effects, behavioral scientists aim to understand between-person heterogeneity in the treatment effect. A natural approach is the familiar linear mixed model. However, directly applying linear mixed models is problematic because potential moderators of the treatment effect are frequently endogenous---that is, may depend on prior treatment. We discuss model interpretation and biases that arise in the absence of additional assumptions when endogenous covariates are included in a linear mixed model. In particular, when there are endogenous covariates, the coefficients no longer have the customary marginal interpretation. However, these coefficients still have a conditional-on-the-random-effect interpretation. We provide an additional assumption that, if true, allows scientists to use standard software to fit linear mixed model with endogenous covariates, and person-specific predictions of effects can be provided. As an illustration, we assess the effect of activity suggestion in the HeartSteps MRT and analyze the between-person treatment effect heterogeneity

UK community health visiting: challenges faced during lean implementation

This paper presents an overview of the challenges and potential of lean implementation for the health visiting service in England and examines the rhetoric and the reality of the situation. It is coauthored by academic researchers and senior service providers so as to embrace the multidimensional issues impacting on this subject. If lean thinking is to be implemented in relation to health visiting, it is important to understand how it is likely to be viewed by practitioners and line managers in settings where it is used. In order to contextualize the discussion, an introduction to the roles, systems, and structures of health visiting are provided. The literature on what lean implementation is, what it means, and in particular the application and potential of the approach to primary care and public health services is reviewed. The process and findings from a focus group convened within a large primary care organization in the National Health Service during their lean implementation is reported. The paper concludes that it is important for staff at all levels to see a clear link between strategic aims and objectives and the planning processes operated by providers and commissioners. It appears that the successful introduction of lean thinking should focus more on productive working and thereby reducing waste. This has the potential to refresh workforce models to ensure that health visiting and other practitioners liberate the use of their specialist knowledge and skills. In a context of enhanced partnership working, the stage is then set for providers to add value to the whole system and together improve service user outcomes