Bridging the Climate Information Gap: A Framework for Engaging Knowledge Brokers and Decision Makers in State Climate Assessments

Large-scale analyses like the National Climate Assessment (NCA) contain a wealth of information critical to national and regional responses to climate change but tend to be insufficiently detailed for action at state or local levels. Many states now engage in assessment processes to meet information needs for local authorities. The goals of state climate assessments (SCAs) should be to provide relevant, actionable information to state and local authorities, and to generate primary sources, build networks and inform stakeholders. To communicate local climate impacts to decision makers, SCAs should express credibility, salience and legitimacy. They can provide information (e.g., case studies, data sets) and connect stakeholders to the NCA and its process. Based on our experience in the Vermont Climate Assessment (VCA), we present a framework to engage decision makers in SCAs using a fluid network of scientific experts and knowledge brokers to conduct subject area prioritization, data analysis and writing. The VCA addressed economic, environmental and social impacts of climate change at local scales to increase resiliency and manage risk. Knowledge brokers communicated VCA findings through their own stakeholder networks. We include a qualitative impact evaluation, and believe our framework for interaction among scientists, knowledge brokers and stakeholders to be an effective structure for SCAs and a transformative experience for students

Cancer Associated Fibroblasts Promote Tumor Growth and Metastasis by Modulating the Tumor Immune Microenvironment in a 4T1 Murine Breast Cancer Model

BACKGROUND:Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS:We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+) T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer

Connection between the Accretion Disk and Jet in the Radio Galaxy 3C 111

We present the results of extensive multi-frequency monitoring of the radio galaxy 3C 111 between 2004 and 2010 at X-ray (2.4--10 keV), optical (R band), and radio (14.5, 37, and 230 GHz) wave bands, as well as multi-epoch imaging with the Very Long Baseline Array (VLBA) at 43 GHz. Over the six years of observation, significant dips in the X-ray light curve are followed by ejections of bright superluminal knots in the VLBA images. This shows a clear connection between the radiative state near the black hole, where the X-rays are produced, and events in the jet. The X-ray continuum flux and Fe line intensity are strongly correlated, with a time lag shorter than 90 days and consistent with zero. This implies that the Fe line is generated within 90 light-days of the source of the X-ray continuum. The power spectral density function of X-ray variations contains a break, with steeper slope at shorter timescales. The break timescale of 13 (+12,-6) days is commensurate with scaling according to the mass of the central black hole based on observations of Seyfert galaxies and black hole X-ray binaries (BHXRBs). The data are consistent with the standard paradigm, in which the X-rays are predominantly produced by inverse Compton scattering of thermal optical/UV seed photons from the accretion disk by a distribution of hot electrons --- the corona --- situated near the disk. Most of the optical emission is generated in the accretion disk due to reprocessing of the X-ray emission. The relationships that we have uncovered between the accretion disk and the jet in 3C 111, as well as in the FR I radio galaxy 3C 120 in a previous paper, support the paradigm that active galactic nuclei and Galactic BHXRBs are fundamentally similar, with characteristic time and size scales proportional to the mass of the central black holeComment: Accepted for publication in ApJ. 18 pages, 17 figures, 11 tables (full machine readable data-tables online in ApJ website

Should Psychotherapy be taught to Psychiatric Residents? A Debate.

Much of this discussion was inspired by a debate held at the 1984 APA Annual Meeting, entitled Does Psychodynamic Theory Have Little Relevance to Contemporary Psychiatric Care? We saw the need for a debate, resident generated, that would address a corollary issue in residency training. Our program will include an introduction, a debate involving statements for the affirmative, that is, that psychotherapy should be taught to psychiatric residents, and two statements for the negative, that psychotherapy should not be taught to psychiatric residents. Concluding remarks will follow. If our title is provocative , if what we have to say inspires you to participate in this critical discussion, either by way of pleasing, stimulating, or offending you, then we have served our purpose well

Searching for the Kuhnian moment : the Black-Scholes-Merton formula and the evolution of modern finance theory

The Black-Scholes-Merton formula has been put to widespread use by options traders because it provides a means of calculating the theoretically 'correct' price of stock options. Traders can therefore see whether the market price of stock options undervalues or overvalues them compared with their hypothetical Black-Scholes-Merton price, before choosing to buy or sell options accordingly. As a consequence of this close relationship between options pricing theory and options pricing practice, a strong performativity loop was activated, whereby market prices quickly converged on the hypothetical Black-Scholes-Merton prices following the dissemination of the formula. The theory has therefore had significant real-world effects, but how should we characterize the initial instinct to derive the theory from a philosophy of science perspective? The two books under review suggest that a Kuhnian reading of the advancement of scientific knowledge might well be the most appropriate. But, on closer inspection, it becomes clear that the publication of the Black-Scholes-Merton formula should not be seen as a Kuhnian moment with paradigm-shaping attributes. It is shown that, at most, the formula acts as an important exemplar which, via its use in the training of options pricing theorists and options pricing practitioners, reinforces the entrenchment of finance theory within the orthodox economics worldview

Increased Turnover of T Lymphocytes in HIV-1 Infection and Its Reduction by Antiretroviral Therapy

The mechanism of CD4+ T cell depletion in human immunodeficiency virus (HIV)-1 infection remains controversial. Using deuterated glucose to label the DNA of proliferating cells in vivo, we studied T cell dynamics in four normal subjects and seven HIV-1–infected patients naive to antiretroviral drugs. The results were analyzed using a newly developed mathematical model to determine fractional rates of lymphocyte proliferation and death. In CD4+ T cells, mean proliferation and death rates were elevated by 6.3- and 2.9-fold, respectively, in infected patients compared with normal controls. In CD8+ T cells, the mean proliferation rate was 7.7-fold higher in HIV-1 infection, but the mean death rate was not significantly increased. Five of the infected patients underwent subsequent deuterated glucose labeling studies after initiating antiretroviral therapy. The lymphocyte proliferation and death rates in both CD4+ and CD8+ cell populations were substantially reduced by 5–11 weeks and nearly normal by one year. Taken together, these new findings strongly indicate that CD4+ lymphocyte depletion seen in AIDS is primarily a consequence of increased cellular destruction, not decreased cellular production

Comparing results of bypass surgery and percutaneous coronary intervention for left main disease by surgical revascularization pump strategy

Objective: We performed a post hoc analysis of the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial to determine the effect an on-versus off-pump strategy had on outcomes when compared with percutaneous coronary intervention. Methods:All randomized patients in EXCEL (n = 1905) were included. The outcomes of interest were the primary end point composite of death from any cause, stroke, or myocardial infarction; the composite study end point or ischemia-driven revascularization; and the rate of death from any cause at 5 years. Event rates were based on Kaplan–Meier estimates in time-to-first-event analyses. Results: Propensity matching resulted in groups of 1142 patients (571 each) for on-pump coronary artery bypass grafting versus percutaneous coronary intervention and 472 patients (236 each) for off-pump coronary artery bypass grafting versus percutaneous coronary intervention. In the on-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point was similar (18.0% vs 22.1%, P = .19) and the composite end point or ischemia-driven revascularization (23.3% vs 31.0%, P = .01) was lower, and mortality (7.6% vs 11.8%, P = .025) was lower in the on-pump coronary artery bypass grafting group at 5 years. In the off-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point (19.4% vs 22.2%, P = .47), composite end point or ischemia-driven revascularization (25.9% vs 34.2%, P = .07), and mortality (12.5% vs 14.2%, P = .59) were similar at 5 years. Conclusions: In the EXCEL trial, on-pump coronary artery bypass grafting was associated with a decreased 5-year rate of the composite outcome of death, stroke, myocardial infarction, or ischemia-driven revascularization, and decreased mortality when compared with percutaneous coronary intervention, whereas outcomes of off-pump coronary artery bypass grafting were similar to percutaneous coronary intervention.</p

Flaring Behavior of the Quasar 3C~454.3 across the Electromagnetic Spectrum

We analyze the behavior of the parsec-scale jet of the quasar 3C~454.3 during pronounced flaring activity in 2005-2008. Three major disturbances propagated down the jet along different trajectories with Lorentz factors $\Gamma>$10. The disturbances show a clear connection with millimeter-wave outbursts, in 2005 May/June, 2007 July, and 2007 December. High-amplitude optical events in the $R$-band light curve precede peaks of the millimeter-wave outbursts by 15-50 days. Each optical outburst is accompanied by an increase in X-ray activity. We associate the optical outbursts with propagation of the superluminal knots and derive the location of sites of energy dissipation in the form of radiation. The most prominent and long-lasting of these, in 2005 May, occurred closer to the black hole, while the outbursts with a shorter duration in 2005 Autumn and in 2007 might be connected with the passage of a disturbance through the millimeter-wave core of the jet. The optical outbursts, which coincide with the passage of superluminal radio knots through the core, are accompanied by systematic rotation of the position angle of optical linear polarization. Such rotation appears to be a common feature during the early stages of flares in blazars. We find correlations between optical variations and those at X-ray and $\gamma$-ray energies. We conclude that the emergence of a superluminal knot from the core yields a series of optical and high-energy outbursts, and that the mm-wave core lies at the end of the jet's acceleration and collimation zone.Comment: 57 pages, 23 figures, 8 tables (submitted to ApJ

Disk-Jet Connection in the Radio Galaxy 3C 120

We present the results of extensive multi-frequency monitoring of the radio galaxy 3C 120 between 2002 and 2007 at X-ray, optical, and radio wave bands, as well as imaging with the Very Long Baseline Array (VLBA). Over the 5 yr of observation, significant dips in the X-ray light curve are followed by ejections of bright superluminal knots in the VLBA images. Consistent with this, the X-ray flux and 37 GHz flux are anti-correlated with X-ray leading the radio variations. This implies that, in this radio galaxy, the radiative state of accretion disk plus corona system, where the X-rays are produced, has a direct effect on the events in the jet, where the radio emission originates. The X-ray power spectral density of 3C 120 shows a break, with steeper slope at shorter timescale and the break timescale is commensurate with the mass of the central black hole based on observations of Seyfert galaxies and black hole X-ray binaries. These findings provide support for the paradigm that black hole X-ray binaries and active galactic nuclei are fundamentally similar systems, with characteristic time and size scales linearly proportional to the mass of the central black hole. The X-ray and optical variations are strongly correlated in 3C 120, which implies that the optical emission in this object arises from the same general region as the X-rays, i.e., in the accretion disk-corona system. We numerically model multi-wavelength light curves of 3C 120 from such a system with the optical-UV emission produced in the disk and the X-rays generated by scattering of thermal photons by hot electrons in the corona. From the comparison of the temporal properties of the model light curves to that of the observed variability, we constrain the physical size of the corona and the distances of the emitting regions from the central BH.Comment: Accepted for publication in the Astrophysical Journal. 28 pages, 21 figures, 2 table