Managerial ownership, entrenchment and innovation

Principle-agent theory suggests managers might under-invest into R&D for reasons of risk tied to project failure, such as reduced remuneration and job loss. However, managers might over-invest into innovation for reasons of growth implying higher remuneration, power and prestige. Using a sample of 1,406 Belgian firms, we find, first, that managers holding no company shares under-invest into R&D compared to owners giving rise to the risk argument. Second, we find an inverse u-shaped relationship between the degree of managerial ownership and R&D. Thus, managers become entrenched, i.e. powerful enough to pursue their own interests. When entrenched, managers do not fear detrimental effects of risky innovation projects on their career, and hence tend to over-invest into innovation. --corporate governance,managerial ownership,entrenchment,innovation,R&D investments

Managerial ownership, entrenchment and innovation.

Principle-agent theory suggests managers might under-invest into R&D for reasons of risk tied to project failure, such as reduced remuneration and job loss. However, managers might over-invest into innovation for reasons of growth implying higher remuneration, power and prestige. Using a sample of 1,406 Belgian firms, we find, first, that managers holding no company shares under-invest into R&D compared to owners giving rise to the risk argument. Second, we find an inverse u-shaped relationship between the degree of managerial ownership and R&D. Thus, managers become entrenched, i.e. powerful enough to pursue their own interests. When entrenched, managers do not fear detrimental effects of risky innovation projects on their career, and hence tend to over-invest into innovation.corporate governance; managerial ownership; entrenchment; innovation; R&D investments;

Managerial ownership, entrenchment and innovation

Principle-agent theory suggests managers might under-invest into R&D for reasons of risk tied to project failure, such as reduced remuneration and job loss. However, managers might over-invest into innovation for reasons of growth implying higher remuneration, power and prestige. Using a sample of 1,406 Belgian firms, we find, first, that managers holding no company shares under-invest into R&D compared to owners giving rise to the risk argument. Second, we find an inverse u-shaped relationship between the degree of managerial ownership and R&D. Thus, managers become entrenched, i.e. powerful enough to pursue their own interests. When entrenched, managers do not fear detrimental effects of risky innovation projects on their career, and hence tend to over-invest into innovation

Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials

The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively)

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown if the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence-densities in %/year were computed for the 'on' and 'off' estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy ('on' versus 'off') as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence-densities 'on' and 'off' hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR 0.56; 95% confidence interval [CI] 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding ('on' versus 'off' hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration

Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials

The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively).publisher: Elsevier articletitle: Choosing wisely: The impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials journaltitle: Thrombosis Research articlelink: http://dx.doi.org/10.1016/j.thromres.2016.11.014 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved.status: publishe

Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): A pooled subgroup analysis of two randomised controlled trials

BACKGROUND: Patients with venous thromboembolism and cancer have a substantial risk of recurrent venous thromboembolism and bleeding during anticoagulant therapy. Although monotherapy with low-molecular-weight heparin is recommended in these patients, in clinical practice many patients with venous thromboembolism and cancer do not receive this treatment. We aimed to assess the efficacy and safety of a single-drug regimen with oral rivaroxaban compared with enoxaparin followed by vitamin K antagonists, in the subgroup of patients with cancer enrolled in the EINSTEIN-DVT and EINSTEIN-PE randomised controlled trials. METHODS: We did a subgroup analysis of patients with active cancer (either at baseline or diagnosed during the study), a history of cancer, or no cancer who were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials. Eligible patients with deep-vein thrombosis (EINSTEIN-DVT) or pulmonary embolism (EINSTEIN-PE) were randomly assigned in a 1:1 ratio to receive rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) or standard therapy (enoxaparin 1\ub70 mg/kg twice daily and warfarin or acenocoumarol; international normalised ratio 2\ub70-3\ub70). Randomisation with a computerised voice-response system was stratified according to country and intended treatment duration (3, 6, or 12 months). The prespecified primary efficacy and safety outcomes of both the trials and this subanalysis were symptomatic recurrent venous thromboembolism and clinically relevant bleeding, respectively. We did efficacy and mortality analyses in the intention-to-treat population, and bleeding analyses for time spent receiving treatment plus 2 days in the safety population (all patients who received at least one dose of study drug). The EINSTEIN-DVT and EINSTEIN-PE studies are registered at ClinicalTrials.gov, numbers NCT00440193 and NCT00439777. FINDINGS: In patients with active cancer (diagnosed at baseline or during treatment), recurrent venous thromboembolism occurred in 16 (5%) of 354 patients allocated to rivaroxaban and 20 (7%) of 301 patients allocated to enoxaparin and vitamin K antagonist (hazard ratio [HR] 0\ub767, 95% CI 0\ub735 to 1\ub730). Clinically relevant bleeding occurred in 48 (14%) of 353 patients receiving rivaroxaban and in 49 (16%) of 298 patients receiving standard therapy (HR 0\ub780, 95% CI 0\ub754 to 1\ub720). Major bleeding occurred in eight (2%) of 353 patients receiving rivaroxaban and in 15 (5%) of 298 patients receiving standard therapy (HR 0\ub742, 95% CI 0\ub718 to 0\ub799). The overall frequency of recurrent venous thromboembolism in patients with only a history of cancer (five [2%] of 233 patients in the rivaroxaban group vs five [2%] of 236 in the standard therapy group; HR 0\ub798, 95% CI 0\ub728-3\ub743) was similar to that of patients without cancer (65 [2%] of 3563 vs 70 [2%] of 3594, respectively; HR 0\ub793, 95% CI 0\ub766-1\ub730), but the frequency was increased in patients with active cancer at baseline (six [2%] of 258 vs eight [4%] of 204, respectively; HR 0\ub762, 95% CI 0\ub721-1\ub779) and most markedly increased in patients whose diagnosis of cancer was made during the study (ten [10%] of 96 vs 12 [12%] of 97, respectively; HR 0\ub780, 95% CI 0\ub734-1\ub788). The overall frequency of major bleeding in patients with only a history of cancer (one [<1%] patient in the rivaroxaban group vs four [2%] patients in the standard therapy group; HR 0\ub723, 95% CI 0\ub703-2\ub706) was similar to that of patients without cancer (31 [1%] vs 53 [1%], respectively; HR 0\ub758, 95% CI 0\ub737-0\ub791), but was increased in patients with active cancer at baseline (five [2%] vs eight [4%], respectively; HR 0\ub747, 95% CI 0\ub715-1\ub745) and was highest in those with cancer diagnosed during the study (three [3%] vs seven [7%], respectively; HR 0\ub733, 95% CI 0\ub708-1\ub731). INTERPRETATION: In patients with active cancer and venous thromboembolism, rivaroxaban had similar efficacy to prevent recurrence of venous thromboembolism and reduced the number major bleeding events compared with treatment with enoxaparin and a vitamin K antagonist, although there was no difference between groups for clinically relevant bleeding. Based on these results, a head-to-head comparison of rivaroxaban with long-term low-molecular-weight heparin in patients with cancer is warranted

Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration

We previously reported that inactivation of the transmembrane taurine transporter (TauT or solute carrier 6a6) causes early retinal degeneration in mice. Compatible with taurine's indispensability for cell volume homeostasis, protein stabilization, cytoprotection, antioxidation, and immuno- and neuromodulation, mice develop multisystemic dysfunctions (hearing loss; liver fibrosis; and behavioral, heart, and skeletal muscle abnormalities) later on. Here, by genetic, cell biologic, in vivo H-1-magnetic resonance spectroscopy and molecular dynamics simulation studies, we conducted in-depth characterization of a novel disorder: human TAUT deficiency. Loss of TAUT function due to a homozygous missense mutation caused panretinal degeneration in 2 brothers. TAUT(p.A78E) still localized in the plasma membrane but is predicted to impact structural stabilization. H-3-taurine uptake by peripheral blood mononuclear cells was reduced by 95%, and taurine levels were severely reduced in plasma, skeletal muscle, and brain. Extraocular dysfunctions were not yet detected, but significantly increased urinary excretion of 8-oxo-7,8-dihydroguanosine indicated generally enhanced (yet clinically unapparent) oxidative stress and RNA oxidation, warranting continuous broad surveillance.-Preising, M. N., Gorg, B., Friedburg, C., Qvartskhava, N., Budde, B. S., Bonus, M., Toliat, M. R., Pfleger, C., Altmuller, J., Herebian, D., Beyer, M., Zollner, H. J., Wittsack, H.-J., Schaper, J., Klee, D., Zechner, U., Nurnberg, P., Schipper, J., Schnitzler, A., Gohlke, H., Lorenz, B., Haussinger, D., Bolz, H. J. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration