Investment and Internal Finance: Asymmetric Information or Managerial Discretion?

This paper examines the relation between cash-flow availability and investment spending in theNetherlands. In particular, we are interested whether managerial discretion and/or asymmetricinformation drive the positive relation between cash-flow and investment spending. This relation ispositive for both firms with low and high investment opportunities. It is however significantly larger forfirms with low investment opportunities suggesting that the managerial-discretion problem is mostimportant in the Dutch setting. Effective corporate-governance may reduce this agency problem.Specific to the Netherlands, firms with low shareholder influence posit a higher cash-flow-investmentsensitivity. The relevance of asymmetric information is confirmed as smaller firms and firms frominformation-sensitive industries show a larger cash-flow-investment sensitivity.The Netherlands;asymmetric information;Investment;financial constraints;managerial discretion

Investment and Internal Finance: Asymmetric Information or Managerial Discretion?

This paper examines the relation between cash-flow availability and investment spending in the Netherlands. In particular, we are interested whether managerial discretion and/or asymmetric information drive the positive relation between cash-flow and investment spending. This relation is positive for both firms with lo

Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: A multicentre, double-blind, randomized, placebo-controlled, parallel-group study

We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin type A (BoNTA; BOTOX); Allergan, Inc., Irvine, CA, USA) for the prophylaxis of chronic tension-type headache (CTTH). Three hundred patients (62.3% female; mean age 42.6 years) enrolled. For the primary endpoint, the mean change from baseline in the number of TTH-free days per month, there was no statistically significant difference between placebo and four BoNTA groups, but a significant difference favouring placebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headache-free days/month; P = 0.007). All treatment groups improved at day 60. Although efficacy was not demonstrated for the primary endpoint, at day 90, more patients in three BoNTA groups had \u3eor=50% decrease in tension headache days than did placebo (

Fractionation of lead in soil by isotopic dilution and sequential extraction

‘Reactivity’ or ‘lability’ of lead is difficult to measure using traditional methods. We investigated the use of isotopic dilution with 204Pb to determine metal reactivity in four soils historically contaminated with contrasting sources of Pb, including (i) petrol-derived Pb, (ii) Pb/Zn minespoil, (iii) long-term sewage sludge application and (iv) 19th century urban waste disposal; total soil Pb concentrations ranged from 217 to 13 600 mg kg–1. A post-spike equilibration period of 3 days and suspension in 5.0 × 10–4 M ethylenediaminetetraacetic acid provided reasonably robust conditions for measuring isotopically exchangeable Pb. However, in acidic organic soils a dilute Ca(NO3)2 electrolyte may be preferable to avoid mobilisation of ‘non-labile’ Pb. Results showed that the reactive pool of soil Pb can be a large proportion of the total soil lead content but varies with the original Pb source. A comparison of isotopic exchangeability with the results of a sequential extraction procedure showed that (isotopically) ‘non-labile’ Pb may be broadly equated with ‘residual’ Pb in organic soils. However, in mineral soils the ‘carbonate’ and ‘oxide-bound’ Pb fractions included non-labile forms of Pb. The individual isotopic signatures of labile and non-labile Pb pools suggested that, despite prolonged contact with soil, differences between the lability of the original contaminant and the native soil Pb may remain

Mass in the back as manifestation of neurofibromatosis type 2

Background: A 13-year-old boy was referred for MR imaging of the thoracolumbar spine to further differentiate a spindle shaped hyporeflective soft tissue mass in the back seen on ultrasonography (not shown) most characteristic for a lipoma. After a closer look at the medical history we learn that the boy is known since the age of 7 with a problem of paresis with atrophy of the left arm. An earlier MR examination of the thoracic outlet showed bilateral soft tissue masses interpreted as diffuse thickening of the plexus brachialis nerves, thus explaining the patient’s complaints, without however a clear etiology being withheld. One year ago a new small mass was excised from the boy’s lip. Anatomopathological analysis revealed an interesting diagnosis: submucosal neurofibroma. Now putting these at first apparently independent events in a greater context, we decided to also realize a MR examination of the brain

Collateral Quality and Loan Default Risk: The Case of Vietnam

In the transition economy of Vietnam, financial market is dominated by banking sector but commercial banks heavily rely on collateral-based lending. While the relationship between collateral and implied credit risk is still in debate, this paper provides additional empirical evidence regarding the heterogeneous effects and transmission channels of collateral characteristics on loan delinquency. Applying instrumental variable probit analysis on a unique dataset of 2295 internal loan accounts in Vietnam, we find the significantly negative impact of collateral quality on the probability of default of consumer loans, supporting the dominance of borrower selection and risk-shifting over lender selection effects. The finding implies that high-quality collateral not only signals more credible borrower but also fosters good behavior in using loan, enabling bank to mitigate adverse selection and moral hazard problems

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia (vol 32, pg 788, 2018)

Following the publication of this article the authors noted that data describing precisely where phosphorylation sites in proteins modulated following JAK1 or JAK3 inhibition in mutant T-ALL samples was not clearly annotated. Therefore an additional sheet has been added to Supplementary Table 2

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Capital structure revisited. Do crisis and competition matter in a Keiretsu corporate structure?

The file attached to this record is the author's final peer reviewed version.open accessWe investigate firm-level determinants of capital structure using a large sample of 4,284 Japanese firms over a nineteen-year period (i.e., over 61,000 firm-year observations), a hitherto less examined sample for this purpose. We conduct our analysis and interpret our findings predominantly within the pecking order, the trade-off and the agency theoretical frameworks. We uncover three new findings. First, our evidence indicates that insights derived from the extant literature on capital structure are cross-national and are applicable in the context of Japan, despite the unique characteristics of Japanese firms. Second, financial crisis significantly impacts the relationship between leverage and firm-level determinants, particularly accentuating the effect of asset tangibility and growth. Third, product market competition significantly impacts the observed relationship between firm-level determinants and leverage. Our results are robust, controlling for the joint effects of competition and crisis