An Analysis of the Corporate Cash Holding Decision

We investigate the tradeoff theory as an explanation for how managers allocate cash to post-spin-off parent and subsidiary firms. Spin-offs provide an opportunity to examine the determinants of cash holdings free from the confounding effects of the pecking order theory. Our results indicate that difference in asset size, sales growth, research and development expenses, net working capital, and leverage significantly affect the difference in cash holdings of post-spin-off entities. These results suggest that cash holdings are decreasing in the ease of raising cash and availability of cash from internal sources, and are increasing in growth opportunities, asymmetric information levels, and financial distress costs

Geochronological studies in Santa Barbara Basin: <SUP>55</SUP>Fe as a unique tracer for particulate settling

Sediments accumulate in the Santa Barbara Basin relatively rapidly: about 3-4 mm yr-1 based on the analysis of varves. These deposits are ideal for studying the applicability of nuclear geochronological techniques in a natural situation. Studies of the depth distribution of several radionuclides, manmade 55Fe and naturally occurring 210Pb and Th isotopes, in recent Santa Barbara sediment layers permit an evaluation of the geochemical behavior of Fe, Pb, and Th in coastal waters and have established the usefulness of 55Fe and 210Pb for dating coastial or near coastal sediments deposited during the last decade and half-century respectively

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis.

ObjectiveTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated.MethodsA randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699).ResultsTofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p&lt;0.05) and chemokines CCL2, CXCL10 and CXCL13 (p&lt;0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p&lt;0.002). Tofacitinib significantly decreased plasma CXCL10 (p&lt;0.005) at Day 28 compared with placebo.ConclusionsTofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response.Trial registration numberNCT00976599

MID3: Mission Impossible or Model-Informed Drug Discovery and Development? Point-Counterpoint Discussions on Key Challenges

MID3: Mission Impossible, or Model‐Informed, Drug Discovery and Development? At the 2019 American Society for Clinical Pharmacology and Therapeutics (ASCPT) annual meeting, point‐counterpoint discussions were held on key challenges that limit, and future directions that enhance the adoption of model‐informed drug discovery and development (MID3) across the drug discovery, development, regulatory, and utilization continuum. We envision that the opportunities discussed and lessons learned from having contrasting perspectives on issues that lack consensus may aid our discipline in more effectively implementing MID3 principles

Collective potential for large N hamiltonian matrix models and free Fisher information

We formulate the planar `large N limit' of matrix models with a continuously infinite number of matrices directly in terms of U(N) invariant variables. Non-commutative probability theory, is found to be a good language to describe this formulation. The change of variables from matrix elements to invariants induces an extra term in the hamiltonian,which is crucual in determining the ground state. We find that this collective potential has a natural meaning in terms of non-commutative probability theory:it is the `free Fisher information' discovered by Voiculescu. This formulation allows us to find a variational principle for the classical theory described by such large N limits. We then use the variational principle to study models more complex than the one describing the quantum mechanics of a single hermitian matrix (i.e., go beyond the so called D=1 barrier). We carry out approximate variational calculations for a few models and find excellent agreement with known results where such comparisons are possible. We also discover a lower bound for the ground state by using the non-commutative analogue of the Cramer-Rao inequality.Comment: 25 pages, late

Practical API Protocol Checking with Access Permissions

Reusable APIs often define usage protocols. We previously developed a sound modular type system that checks compliance with typestate-based protocols while affording a great deal of aliasing flexibility. We also developed Plural, a prototype tool that embodies our approach as an automated static analysis and includes several extensions we found useful in practice. This paper evaluates our approach along the following dimensions: (1) We report on experience in specifying relevant usage rules for a large Java standard API with our approach. We also specify several other Java APIs and identify recurring patterns. (2) We summarize two case studies in verifying third-party open-source code bases with few false positives using our tool. We discuss how tool shortcomings can be addressed either with code refactorings or extensions to the tool itself. These results indicate that our approach can be used to specify and enforce real API protocols in practice

Thirty Years After Michael E. Porter: What Do We Know About Business Exit?

Although a business exit is an important corporate change initiative, the buyer’s side seems to be more appealing to management researchers than the seller’s because acquisitions imply growth, i.e., success. Yet from an optimistic viewpoint, business exit can effectively create value for the selling company. In this paper we attempt to bring the relevance of the seller’s side back into our consciousness by asking: What do we know about business exit? We start our exploration with Porter (1976), focusing on literature that investigates the antecedents of, barriers to, and outcomes of business exit. We also include studies from related fields such as finance and economics.1 Through this research we determine three clusters of findings: factors promoting business exit, exit barriers, and exit outcomes. Overall, it is the intention of this paper to highlight the importance of business exit for research and practice. Knowing what we know about business exits and their high financial value we should bear in mind that exit need not mean failure but a new beginning for a corporation

Studies of the Response of the Prototype CMS Hadron Calorimeter, Including Magnetic Field Effects, to Pion, Electron, and Muon Beams

We report on the response of a prototype CMS hadron calorimeter module to charged particle beams of pions, muons, and electrons with momenta up to 375 GeV/c. The data were taken at the H2 and H4 beamlines at CERN in 1995 and 1996. The prototype sampling calorimeter used copper absorber plates and scintillator tiles with wavelength shifting fibers for readout. The effects of a magnetic field of up to 3 Tesla on the response of the calorimeter to muons, electrons, and pions are presented, and the effects of an upstream lead tungstate crystal electromagnetic calorimeter on the linearity and energy resolution of the combined calorimetric system to hadrons are evaluated. The results are compared with Monte Carlo simulations and are used to optimize the choice of total absorber depth, sampling frequency, and longitudinal readout segmentation.Comment: 89 pages, 41 figures, to be published in NIM, corresponding author: P de Barbaro, [email protected]

Tofacitinib versus methotrexate in rheumatoid arthritis

Background : Methotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate. Methods : We randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (>= 70% reduction in the number of both tender and swollen joints and >= 70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician). Results : Mean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [ P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels. Conclusions : In patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events