Better Together: Engaging Stakeholders in Learning and Leadership to Guide Foundation Resources Toward Adaptive Systems Change

In 2014, the Kansas Health Foundation brought together a group of knowledgeable stakeholders from a multitude of specialties to focus on reducing tobacco use specifically among Kansans with mental illness. Over 15 months, the group and the foundation worked to learn deeply about the issue and inform action that could be taken on individual, organizational, and systemic levels. The wealth of knowledge and experience brought by each participant to the discussion and learning about this complex issue, together from a range of perspectives, resulted in a more productive dialogue. The model proved very effective, as evidenced by the group’s success in achieving a number of policy, system, and environmental changes — including expanding cessation benefits available under Medicaid in Kansas — and could be replicated by any foundation. The foundation continues to work collaboratively on this issue and discover more about what is effective in reducing tobacco use. What it learned alongside its community partners has powerfully informed the foundation’s approach to this work and has resulted in meaningful change, at multiple levels, in the behavioral health system

Emergent Systems Energy Laws for Predicting Myosin Ensemble Processivity

In complex systems with stochastic components, systems laws often emerge that describe higher level behavior regardless of lower level component configurations. In this paper, emergent laws for describing mechanochemical systems are investigated for processive myosin-actin motility systems. On the basis of prior experimental evidence that longer processive lifetimes are enabled by larger myosin ensembles, it is hypothesized that emergent scaling laws could coincide with myosin-actin contact probability or system energy consumption. Because processivity is difficult to predict analytically and measure experimentally, agent-based computational techniques are developed to simulate processive myosin ensembles and produce novel processive lifetime measurements. It is demonstrated that only systems energy relationships hold regardless of isoform configurations or ensemble size, and a unified expression for predicting processive lifetime is revealed. The finding of such laws provides insight for how patterns emerge in stochastic mechanochemical systems, while also informing understanding and engineering of complex biological systems

Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network

Drosophila provides an inexpensive and quantitative platform for measuring whole animal drug response. A complementary approach is virtual screening, where chemical libraries can be efficiently screened against protein target(s). Here, we present a unique discovery platform integrating structure-based modeling with Drosophila biology and organic synthesis. We demonstrate this platform by developing chemicals targeting a Drosophila model of Medullary Thyroid Cancer (MTC) characterized by a transformation network activated by oncogenic dRetM955T. Structural models for kinases relevant to MTC were generated for virtual screening to identify unique preliminary hits that suppressed dRetM955T-induced transformation. We then combined features from our hits with those of known inhibitors to create a ‘hybrid’ molecule with improved suppression of dRetM955T transformation. Our platform provides a framework to efficiently explore novel kinase inhibitors outside of explored inhibitor chemical space that are effective in inhibiting cancer networks while minimizing whole body toxicity

A Slope-Based Method for Least Cost Tolerance Allocation

In this paper, a new methodology is presented to solve the tolerance allocation-process selection problem simultaneously The prob lem is modeled using discrete and continuous variables and is transformed into a model with only continuous variables by defining an efficient tolerance-cost curve for each component Since the efficient tolerance-cost curve is neither convex nor concave, nonlinear programming method ologies cannot be directly applied The tolerance-cost curve is piecewise linearly approximated and an efficient methodology is developed to solve the problem The method starts with a solution which minimizes the objective function value but is not feasible The infeasibility is iteratively reduced in a way that the increase in the objective function value is minimal Computational analysis indicates that the method is very robust and requires negligible CPU timeYeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The Size and Growth of the Hidden Economy in Norway

The present size of the hidden economy in Norway is between 4 and 6 percent of GDP, of which hidden labor income constitutes about half. A survey approach reveals that 415 of the population is of the opinion that people in general accept income from moonlighting that is not reported, and 213 believes that this share of acceptance is on the increase. Furthermore, surveys clearly show that hidden labor services are of satisfactory quality, that they mainly are paid for in cash, but with checks being increasingly used, and that buyers find it easier to obtain services from the hidden labor market than from the regular one. A shortening of the work week in order to alleviate unemployment may result in an increased supply of hidden labor

Thromboprophylaxis Is Associated With Reduced Post-hospitalization Venous Thromboembolic Events in Patients With Inflammatory Bowel Diseases

Background & Aims Patients with inflammatory bowel diseases (IBDs) have increased risk for venous thromboembolism (VTE); those who require hospitalization have particularly high risk. Few hospitalized patients with IBD receive thromboprophylaxis. We analyzed the frequency of VTE after IBD-related hospitalization, risk factors for post-hospitalization VTE, and the efficacy of prophylaxis in preventing post-hospitalization VTE. Methods In a retrospective study, we analyzed data from a multi-institutional cohort of patients with Crohn's disease or ulcerative colitis and at least 1 IBD-related hospitalization. Our primary outcome was a VTE event. All patients contributed person-time from the date of the index hospitalization to development of VTE, subsequent hospitalization, or end of follow-up. Our main predictor variable was pharmacologic thromboprophylaxis. Cox proportional hazard models adjusting for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results From a cohort of 2788 patients with at least 1 IBD-related hospitalization, 62 patients developed VTE after discharge (2%). Incidences of VTE at 30, 60, 90, and 180 days after the index hospitalization were 3.7/1000, 4.1/1000, 5.4/1000, and 9.4/1000 person-days, respectively. Pharmacologic thromboprophylaxis during the index hospital stay was associated with a significantly lower risk of post-hospitalization VTE (HR, 0.46; 95% CI, 0.22–0.97). Increased numbers of comorbidities (HR, 1.30; 95% CI, 1.16–1.47) and need for corticosteroids before hospitalization (HR, 1.71; 95% CI, 1.02–2.87) were also independently associated with risk of VTE. Length of hospitalization or surgery during index hospitalization was not associated with post-hospitalization VTE. Conclusions Pharmacologic thromboprophylaxis during IBD-related hospitalization is associated with reduced risk of post-hospitalization VTE.National Institutes of Health (U.S.) (U54-LM008748

Evidence and Ideology in Macroeconomics: The Case of Investment Cycles

The paper reports the principal findings of a long term research project on the description and explanation of business cycles. The research strongly confirmed the older view that business cycles have large systematic components that take the form of investment cycles. These quasi-periodic movements can be represented as low order, stochastic, dynamic processes with complex eigenvalues. Specifically, there is a fixed investment cycle of about 8 years and an inventory cycle of about 4 years. Maximum entropy spectral analysis was employed for the description of the cycles and continuous time econometrics for the explanatory models. The central explanatory mechanism is the second order accelerator, which incorporates adjustment costs both in relation to the capital stock and the rate of investment. By means of parametric resonance it was possible to show, both theoretically and empirically how cycles aggregate from the micro to the macro level. The same mathematical tool was also used to explain the international convergence of cycles. I argue that the theory of investment cycles was abandoned for ideological, not for evidential reasons. Methodological issues are also discussed

Normalization of Plasma 25-Hydroxy Vitamin D Is Associated with Reduced Risk of Surgery in Crohn’s Disease

available in PMC 2014 August 01AB Background: Vitamin D may have an immunologic role in Crohn's disease (CD) and ulcerative colitis (UC). Retrospective studies suggested a weak association between vitamin D status and disease activity but have significant limitations. Methods: Using a multi-institution inflammatory bowel disease cohort, we identified all patients with CD and UC who had at least one measured plasma 25-hydroxy vitamin D (25(OH)D). Plasma 25(OH)D was considered sufficient at levels >=30 ng/mL. Logistic regression models adjusting for potential confounders were used to identify impact of measured plasma 25(OH)D on subsequent risk of inflammatory bowel disease-related surgery or hospitalization. In a subset of patients where multiple measures of 25(OH)D were available, we examined impact of normalization of vitamin D status on study outcomes. Results: Our study included 3217 patients (55% CD; mean age, 49 yr). The median lowest plasma 25(OH)D was 26 ng/mL (interquartile range, 17-35 ng/mL). In CD, on multivariable analysis, plasma 25(OH)D =30 ng/mL. Similar estimates were also seen for UC. Furthermore, patients with CD who had initial levels <30 ng/mL but subsequently normalized their 25(OH)D had a reduced likelihood of surgery (odds ratio, 0.56; 95% confidence interval, 0.32-0.98) compared with those who remained deficient. Conclusion: Low plasma 25(OH)D is associated with increased risk of surgery and hospitalizations in both CD and UC, and normalization of 25(OH)D status is associated with a reduction in the risk of CD-related surgery. (C) Crohn's & Colitis Foundation of America, Inc

MicroRNAs and Developmental Robustness: A New Layer Is Revealed

MicroRNAs provide a new layer of regulation to ensure that a developmental program of programmed cell death yields a reproducible outcome in spite of perturbations to the system