Competing With the NYSE

We study the stock exchange rivalry between the New York Stock Exchange (NYSE) and the Consolidated Stock Exchange (Consolidated) from 1885 to 1926 using a new database of bid-ask spreads and stock data collected from The New York Times and other primary sources. The magnitude of this important, but largely forgotten rivalry was substantial. From 1885 to 1895, the ratio of Consolidated to NYSE volume averaged 40 percent and reached as high as 60 percent. The market share of the Consolidated averaged 23 percent for approximately 40 years. The Consolidated focused on the relatively liquid securities on the NYSE as measured by bid-ask spreads and trading volume. Our results suggest that NYSE bid-ask spreads fell by more than 10 percent when the Consolidated began to trade NYSE stocks while bid-ask spreads for our quasicontrol group of stocks trading on the Boston Stock Exchange remain unchanged. The effect persisted over the entire history of the stock market rivalry until a series of scandals and investigations of the Consolidated by state regulators led to the demise of the exchange in the 1920s. The analysis suggests three conclusions: (1) the NYSE has faced significant long-run competition (2) the NYSE may be susceptible to a similar level of competition in the future and (3) that the Consolidated may have improved the efficiency of stock prices by contributing to the price discovery process.

A randomized placebo-controlled trial of methotrexate in psoriatic arthritis.

OBJECTIVE: MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA. METHODS: A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA. The primary outcome was PsA response criteria (PsARC). Other outcomes included ACR20, DAS-28 and their individual components. Missing data were imputed using multiple imputation methods. Treatments were compared using logistic regression analysis (adjusted for age, sex, disease duration and, where appropriate, individual baseline scores). RESULTS: Four hundred and sixty-two patients were screened and 221 recruited. One hundred and nine patients received MTX and 112 received placebo. Forty-four patients were lost to follow-up (21 MTX, 23 placebo). Twenty-six patients discontinued treatment (14 MTX, 12 placebo). Comparing MTX with placebo in all randomized patients at 6 months showed no significant effect on PsARC [odds ratio (OR) 1.77, 95% CI 0.97, 3.23], ACR20 (OR 2.00, 95% CI 0.65, 6.22) or DAS-28 (OR 1.70, 95% CI 0.90, 3.17). There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ and pain. The only benefits of MTX were reductions in patient and assessor global scores and skin scores at 6 months (P = 0.03, P < 0.001 and P = 0.02, respectively). There were no unexpected adverse events. CONCLUSIONS: This trial of active PsA found no evidence for MTX improving synovitis and consequently raises questions about its classification as a disease-modifying drug in PsA. Trial registration. Current Controlled Trials, www.controlled-trials.com, ISRCTN:54376151

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

Arctic shipping and polar seaways

Climate change in the Arctic triggered a series of discourses about the opening-up of a previously unreachable region. Navigation remains however difficult in the Arctic, transits are still very limited, as sea-ice still is a major constraint. How did the development policies of both the North West Passage and the Northern Sea Route unfold ? What are the recent trends in Arctic shipping ?

Characterization of Ice Adhesion: Approaches and Modes of Loading

Airborne structures are vulnerable to atmospheric icing in cold weather operation conditions. Most of the ice adhesion-related works have focused on mechanical ice removal strategies because of practical considerations, while limited literature is available for a fundamental understanding of the ice adhesion process. Here, we present fracture mechanics-based approaches to characterize interfacial fracture parameters for the tensile and shear behavior of a typical ice/aluminum interface. An experimental framework employing single cantilever beam, direct shear, and push-out shear tests were developed to achieve near mode-I and near mode-II fracture conditions at the interface. Both analytical (beam bending and shear-lag analysis), and numerical (finite element analysis incorporating cohesive zone method) models were used to extract mode-I and II interfacial fracture parameters. The combined experimental and numerical results, as well as surveying published results for the direct shear and push-out shear tests, showed that mode-II interfacial strength and toughness could be significantly affected by the test method due to geometrically induced interfacial residual stress. As a result, the apparent toughness of the zero-angle push-out test could reach an order of magnitude higher than those derived from direct shear tests. Moreover, it was found that the interfacial ice adhesion is fracture mode insensitive and roughness insensitive for tensile and shear modes, for the observed modes of failures in this stud

Expression and regulation of HIF-1alpha in macrophages under inflammatory conditions; significant reduction of VEGF by CaMKII inhibitor

<p>Abstract</p> <p>Background</p> <p>Macrophages expressing the pro-angiogenic transcription factor hypoxia-inducible factor (HIF)-1alpha have been demonstrated in rheumatoid arthritis (RA) in the synovial tissue. Aim of the present study was to investigate intracellular signal transduction regulation of pro-inflammatory HIF-1 alpha expression in macrophages to identify possible new intervention strategies. We investigated the effects of CaMKII-inhibitors amongst other kinase inhibitors, on HIF-1 alpha expression and downstream production of pro-angiogenic factors in macrophages.</p> <p>Methods</p> <p>Differentiated THP-1 cells and synovial fluid (SF) macrophages were stimulated with 1 μg/ml LPS with or without pretreatment with specific inhibitors of the ERK pathway (PD98059), the PI3K pathway (LY294002), and the CaMKII pathway (KN93 and SMP-114). mRNA and protein expression of HIF-1 alpha, VEGF, MMP-9, and IL-8 was measured in cell lysates and cell supernatants.</p> <p>Results</p> <p>HIF-1 alpha protein expression in LPS-stimulated THP-1 macrophages could be blocked by ERK- and PI3K-inhibitors, but also by the CaMKII inhibitor KN93. THP-1 and SF macrophages produced high levels of VEGF, IL-8, and MMP-9, and VEGF protein production was significantly inhibited by PI3K-inhibitor, and by both CaMKII inhibitors. LPS stimulation in an hypoxic environment did not change VEGF levels, suggesting that LPS induced VEGF production in macrophages is more important than the hypoxic induction.</p> <p>Conclusions</p> <p>Expression of HIF-1 alpha and downstream effects in macrophages are regulated by ERK-, PI3K, but also by CaMKII pathways. Inhibition of HIF-1α protein expression and significant inhibition of VEGF production in macrophages was found using CaMKII inhibitors. This is an unknown but very interesting effect of the CaMKII inhibitor SMP-114, which has been in clinical trial as DMARD for the treatment of RA. This effect may contribute to the anti-arthritic effects of SMP-114.</p

Physical activity but not sedentary activity is reduced in primary Sjögren’s syndrome

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren’s syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594–3158) versus 3708 (1732–8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135–375) versus 343 (223–433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0–480) versus 1560 (570–3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0–480) versus 480 (0–1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS

A methodological framework to distinguish spectrum effects from spectrum biases and to assess diagnostic and screening test accuracy for patient populations: Application to the Papanicolaou cervical cancer smear test

<p>Abstract</p> <p>Background</p> <p>A spectrum effect was defined as differences in the sensitivity or specificity of a diagnostic test according to the patient's characteristics or disease features. A spectrum effect can lead to a spectrum bias when subgroup variations in sensitivity or specificity also affect the likelihood ratios and thus post-test probabilities. We propose and illustrate a methodological framework to distinguish spectrum effects from spectrum biases.</p> <p>Methods</p> <p>Data were collected for 1781 women having had a cervical smear test and colposcopy followed by biopsy if abnormalities were detected (the reference standard). Logistic models were constructed to evaluate both the sensitivity and specificity, and the likelihood ratios, of the test and to identify factors independently affecting the test's characteristics.</p> <p>Results</p> <p>For both tests, human papillomavirus test, study setting and age affected sensitivity or specificity of the smear test (spectrum effect), but only human papillomavirus test and study setting modified the likelihood ratios (spectrum bias) for clinical reading, whereas only human papillomavirus test and age modified the likelihood ratios (spectrum bias) for "optimized" interpretation.</p> <p>Conclusion</p> <p>Fitting sensitivity, specificity and likelihood ratios simultaneously allows the identification of covariates that independently affect diagnostic or screening test results and distinguishes spectrum effect from spectrum bias. We recommend this approach for the development of new tests, and for reporting test accuracy for different patient populations.</p