What Does CEOs’ Personal Leverage Tell Us About Corporate Leverage?

We find that firms behave remarkably similarly to how their CEOs behave personally when it comes to leverage choices. We start our analysis by compiling a comprehensive sample of home purchases and financings among S&P 1,500 CEOs. Debt financing in a CEO’s most recent home purchase is used as a revealed preference of the CEO’s personal attitude towards debt. We find a robust positive relation between personal and corporate leverage. We also find that firms tend to hire CEOs with a similar personal attitude towards debt as the previous CEO. When the new and previous CEOs have different personal preferences, corporate leverage changes in the direction of the new CEO’s personal leverage. These results support a model with endogenous matching of CEOs to firms. We also find that the positive relation between CEOs’ personal leverage and corporate leverage is stronger in firms with poor governance, suggesting that CEOs imprint their personal preferences on the firms they manage when they are able to do so. These results suggest that heterogeneity in CEOs’ personal attitudes towards debt partly explains differences in corporate capital structures, and suggest more generally that an analysis of CEOs’ personalities and personal traits may provide important information about the financial policies of the firms they manage.Corporate leverage; personal leverage; CEO characteristics

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

Revealing stromal and lymphoid sources of Col3a1-expression during inflammation using a novel reporter mouse

One of the earliest signs of dysregulation of the homeostatic process of fibrosis, associated with pathology in chronic conditions such as rheumatoid arthritis (RA), is the overexpression of collagen type III (COL-3). Critically, there is still relatively little known regarding the identity of the cell types expressing the gene encoding COL-3 (Col3a1). Identifying and characterising Col3a1-expressing cells during the development of fibrosis could reveal new targets for diagnosis and treatment of fibrosis-related pathologies. As such, a reporter mouse expressing concomitantly Col3a1 and mKate-2, a fluorescent protein, was generated. Using models of footpad inflammation, we demonstrated its effectiveness as a tool to measure the expression of COL-3 during the repair process and provided an initial characterisation of some of the stromal and immune cells responsible for Col3a1 expression

The Potential of MLN3651 in Combination with Selumetinib as a Treatment for Merlin-Deficient Meningioma

Meningioma is the most common primary intracranial tumour, and surgical resection is the main therapeutic option. Merlin is a tumour suppressor protein that is frequently mutated in meningioma. The activity of the E3 ubiquitin ligase complex, CRL4-DCAF1, and the Raf/MEK/ERK scaffold protein Kinase suppressor of Ras 1 (KSR1) are upregulated in Merlin-deficient tumours, which drives tumour growth. Identifying small molecules that inhibit these key pathways may provide an effective treatment option for patients with meningioma. We used meningioma tissue and primary cells derived from meningioma tumours to investigate the expression of DDB1 and Cullin 4-associated factor 1 (DCAF1) and KSR1, and confirmed these proteins were overexpressed. We then used primary cells to assess the therapeutic potential of MLN3651, a neddylation inhibitor which impacts the activity of the CRL family of E3 ubiquitin ligases and the MAPK/ERK kinase (MEK1/2) inhibitor selumetinib. MLN3651 treatment reduced proliferation and activated apoptosis, whilst increasing Raf/MEK/ERK pathway activation. The combination of MLN3651 and the MEK1/2 inhibitor selumetinib prevented the increase in Raf/MEK/ERK activity, and had an additive effect compared with either treatment alone. Therefore, the combined targeting of CRL4-DCAF1 and Raf/MEK/ERK activity represents an attractive novel strategy in the treatment of Merlin-deficient meningioma.</jats:p

Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV1-associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV1 risk alleles (p = 1.3x10-5; β = 0.12, 95% CI = 0.06–0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure

Endotypes of difficult-to-control asthma in inner-city African American children

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6–17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population

PREP1 tumor suppressor protects the late-replicating DNA by controlling its replication timing and symmetry

The synthesis of middle-to-late-replicating DNA can be affected independently of the rest of the genome by down-regulating the tumor suppressor PREP1 (PKNOX1). Indeed, DNA combing shows that PREP1 down-regulation affects DNA replication rate, increases the number of simultaneously firing origins and the asymmetry of DNA replication, leading to DNA damage. Genome-wide analysis of replication timing by Repli-seq shows that, upon PREP1 down-regulation, 25% of the genome is replicated earlier in the S-phase. The targeted DNA sequences correspond to Lamin-Associated Domains (LADs), and include late-replicating (LRRs) and temporal transition regions (TTRs). Notably, the distribution of PREP1 DNA binding sites and of its target genes indicates that DNA replication defects are independent of the overall PREP1 transcriptional activity. Finally, PREP1 down-regulation causes a substantial decrease in Lamin B1 levels. This suggests that DNA is released from the nuclear lamina earlier than in the control cells and is available for replication, thus explaining timing defects and DNA damage.This is the first evidence that the replication timing of a specific fraction of the human genome is affected by PREP1 tumor suppressor. This previously unknown function might significantly contribute to the genomic instability observed in human tumors

Razvoj i vrednovanje dvoslojnih tableta propranolol hidroklorida

The objective of the present research was to develop a bilayer tablet of propranolol hydrochloride using superdisintegrant sodium starch glycolate for the fast release layer and water immiscible polymers such as ethyl cellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. In vitro dissolution studies were carried out in a USP 24 apparatus I. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 12 hrs from the sustaining layer of matrix embedded tablets. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p 0.005) in the amount of drug released after 12 h from optimized formulations was observed.U radu je opisan razvoj dvoslojnih tableta propranolol hidroklorida, koristeći superdezintegrator škrob glikolat natrij u sloju za brzo oslobađanje i polimere koji se ne miješaju s vodom (etil celuloza, Eudragit RLPO i Eudragit RSPO) u sloju za usporeno oslobađanje. In vitro oslobađanje praćeno je u USP aparatu I te je uočeno početno naglo oslobađanje ljekovite tvari iza kojeg slijedi polagano oslobađanje tijekom 12 sati. In vitro kinetika oslobađanja prati Higouchijev model, dok mehanizam kontroliranog oslobađanja ne slijedi Fickov zakon poslije početnog naglog oslobađanja. FT-IR studije ukazuju da nema interakcije između ljekovite tvari i polimera upotrebljenih u oblikovanju. Statistička analiza (ANOVA) nije pokazala značajne razlike u kumulativnoj količini oslobođenog lijeka iz optimiranih formulacija poslije 15 minuta i polije 12 h

Nutritional status and functional capacity of hospitalized elderly

Background: The nutritional status of the aging individual results from a complex interaction between personal and environmental factors. A disease influences and is influenced by the nutritional status and the functional capacity of the individual. We asses the relationship between nutritional status and indicators of functional capacity among recently hospitalized elderly in a general hospital.Methods: A cross-sectional study was done with 240 elderly (women, n = 127 and men, n = 113) hospitalized in a hospital that provides care for the public and private healthcare systems. The nutritional status was classified by the MNA (Mini Nutritional Assessment) into: malnourished, risk of malnutrition and without malnutrition (adequate). The functional autonomy indicators were obtained by the self-reported Instrumental Activity of Daily Living (IADL) and Activity of Daily Living (ADL) questionnaire. The chi-square test was used to compare the proportions and the level of significance was 5%.Results: Among the assessed elderly, 33.8% were classified as adequate regarding nutritional status; 37.1% were classified as being at risk of malnutrition and 29.1% were classified as malnourished. All the IADL and ADL variables assessed were significantly more deteriorated among the malnourished individuals. Among the ADL variables, eating partial (42.9%) or complete (12.9%) dependence was found in more than half of the malnourished elderly, in 13.4% of those at risk of malnutrition and in 2.5% of those without malnutrition.Conclusion: There is an interrelationship between the nutritional status of the elderly and reduced functional capacity

Concordance between Clinical Practice and Published Evidence: Findings from The National Dental Practice-Based Research Network

Documenting the gap between what is occurring in clinical practice and what published research suggests is an important step toward improving care. This study quantified concordance between clinical practice and published evidence across preventive, diagnostic and treatment procedures among a sample of dentists in the National Dental Practice-Based Research Network