Endowment Effects Within Corporate Agency Relationships

Behavioral economics is an increasingly prominent field within corporate law scholarship. A particularly noteworthy behavioral bias is the endowment effect – the observed differential between an individual\u27s willingness to pay to obtain an entitlement and her willingness to accept to part with one. Should endowment effects pervade corporate contexts, they would significantly complicate much common wisdom within business law, such as the presumed optimality of ex ante agreements. Existing research, however, does not adequately address the extent to which people manifest endowment effects within agency relationships. This article presents an experimental test for endowment effects for subjects situated in an agency relationship that typifies many firms. We find that subjects do not exhibit significant endowment effects. An additional experimental test suggests that this finding may be largely due to framing: subjects situated as agents may view entitlements principally in terms of exchange value, thereby dampening endowment

Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System.

Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy.

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

Evolution of magnetized, differentially rotating neutron stars: Simulations in full general relativity

We study the effects of magnetic fields on the evolution of differentially rotating neutron stars, which can form in stellar core collapse or binary neutron star coalescence. Magnetic braking and the magnetorotational instability (MRI) both redistribute angular momentum; the outcome of the evolution depends on the star's mass and spin. Simulations are carried out in axisymmetry using our recently developed codes which integrate the coupled Einstein-Maxwell-MHD equations. For initial data, we consider three categories of differentially rotating, equilibrium configurations, which we label normal, hypermassive and ultraspinning. Hypermassive stars have rest masses exceeding the mass limit for uniform rotation. Ultraspinning stars are not hypermassive, but have angular momentum exceeding the maximum for uniform rotation at the same rest mass. We show that a normal star will evolve to a uniformly rotating equilibrium configuration. An ultraspinning star evolves to an equilibrium state consisting of a nearly uniformly rotating central core, surrounded by a differentially rotating torus with constant angular velocity along magnetic field lines, so that differential rotation ceases to wind the magnetic field. In addition, the final state is stable against the MRI, although it has differential rotation. For a hypermassive neutron star, the MHD-driven angular momentum transport leads to catastrophic collapse of the core. The resulting rotating black hole is surrounded by a hot, massive, magnetized torus undergoing quasistationary accretion, and a magnetic field collimated along the spin axis--a promising candidate for the central engine of a short gamma-ray burst. (Abridged)Comment: 27 pages, 30 figure

Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders

Background: A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods: Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion: This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised

Chemodynamics of Compact Stellar Systems in NGC 5128: How similar are Globular Clusters, Ultra-Compact Dwarfs, and Dwarf Galaxies?

Velocity dispersion measurements are presented for luminous GCs in NGC 5128 derived from high-res. UVES spectra. The measurements are made with the pPXF code that parametrically recovers line-of-sight velocity dispersions. Combining the measured velocity dispersions with surface photometry and structural parameter data from HST enables both dynamical masses and M/L ratios to be derived. The fundamental plane relations of these clusters are investigated in order to fill the apparent gap between the relations of Local Group GCs and more massive early-type galaxies. It is found that the properties of these massive stellar systems match those of nuclear clusters in dwarf elliptical galaxies and UCDs better than those of Local Group GCs, and that all objects share similarly old (>8 Gyr) ages, suggesting a possible link between the formation and evolution of dE,Ns, UCDs and massive GCs. We find a very steep correlation between dynamical (M/L) ratio and dynamical mass of the form (M/L)_dyn ~ M_dyn^(0.24+/-0.02) above M_dyn = 2x10^6 Msol. Formation scenarios are investigated with a chemical abundance analysis using absorption line strengths calibrated to the Lick/IDS index system. The results lend support to two scenarios contained within a single general formation scheme. Old, massive, super-solar [alpha/Fe] systems are formed on short (<100 Myr) timescales through the merging of single-collapse GCs which themselves are formed within single, giant molecular clouds. More intermediate- and old-aged (~3-10 Gyr), solar- to sub-solar [alpha/Fe] systems are formed on much longer (~Gyr) timescales through the stripping of dE,Ns in the 10^13-10^15 Msol potential wells of massive galaxies and galaxy clusters.Comment: 12 pages (ApJ style) with 11 figures and 7 tables, accepted for publication in Ap

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates &gt;= 98% of peripheral immune cells with &gt;= 4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

Systemic immunity is required for effective cancer immunotherapy

Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection

MetaCyto: A Tool for Automated Meta-analysis of Mass and Flow Cytometry Data

While meta-analysis has demonstrated increased statistical power and more robust estimations in studies, the application of this commonly accepted methodology to cytometry data has been challenging. Different cytometry studies often involve diverse sets of markers. Moreover, the detected values of the same marker are inconsistent between studies due to different experimental designs and cytometer configurations. As a result, the cell subsets identified by existing auto-gating methods cannot be directly compared across studies. We developed MetaCyto for automated meta-analysis of both flow and mass cytometry (CyTOF) data. By combining clustering methods with a silhouette scanning method, MetaCyto is able to identify commonly labeled cell subsets across studies, thus enabling meta-analysis. Applying MetaCyto across a set of ten heterogeneous cytometry studies totaling 2,926 samples enabled us to identify multiple cell populations exhibiting differences in abundance between demographic groups

The Extended Environment of M17: A Star Formation History

M17 is one of the youngest and most massive nearby star-formation regions in the Galaxy. It features a bright H II region erupting as a blister from the side of a giant molecular cloud (GMC). Combining photometry from the Spitzer GLIMPSE survey with complementary infrared (IR) surveys, we identify candidate young stellar objects (YSOs) throughout a 1.5 deg x 1 deg field that includes the M17 complex. The long sightline through the Galaxy behind M17 creates significant contamination in our YSO sample from unassociated sources with similar IR colors. Removing contaminants, we produce a highly-reliable catalog of 96 candidate YSOs with a high probability of association with the M17 complex. We fit model spectral energy distributions to these sources and constrain their physical properties. Extrapolating the mass function of 62 intermediate-mass YSOs (M >3 Msun), we estimate that >1000 stars are in the process of forming in the extended outer regions of M17. From IR survey images from IRAS and GLIMPSE, we find that M17 lies on the rim of a large shell structure ~0.5 deg in diameter (~20 pc at 2.1 kpc). We present new maps of CO and 13CO (J=2-1) emission, which show that the shell is a coherent, kinematic structure associated with M17 at v = 19 km/s. The shell is an extended bubble outlining the photodissociation region of a faint, diffuse H II region several Myr old. We provide evidence that massive star formation has been triggered by the expansion of the bubble. The formation of the massive cluster ionizing the M17 H II region itself may have been similarly triggered. We conclude that the star formation history in the extended environment of M17 has been punctuated by successive waves of massive star formation propagating through a GMC complex.Comment: 31 pages, 15 figures, accepted for publication in ApJ. For a version with higher-quality figures, see http://www.astro.wisc.edu/glimpse/Povich2009_M17.pd