bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Keys to Success in Spinoffs
Authors: Emrick Craig , Khorana Ajay , Shivdasani Anil , Ventouras Peter 
Published: October 2017

Corporate restructurings accomplished through spinoffs have long been a key tool for management to unlock shareholder value. In 2016, global spinoff volume reached $117 billion, and spinoff activity continues to unfold at a similar pace in 2017, with Hilton, Xerox, Alcoa, Johnson Controls, and Danaher all recently completing major transactions.Spinoffs are often designed to increase strategic focus and discipline in the allocation of capital, enabling companies to respond more effectively to opportunities that create shareholder value, including transformational M&A. And intensifying shareholder activist pressure, along with favorable debt market conditions, has provided significant momentum to spinoff activity. In fact, almost 20% of the companies that announced spinoffs in the past five years were subject to some form of prior activist engagement. Moreover, part of the impetus for such activism can be traced to the record M&A volume of the past few years, which has added to investor demand for many acquisitive companies to consider shedding businesses that are no longer a strategic fit.But even with all this M&A activity, opportunities for unlocking value through spinoffs have not been as abundant or readily identified as in the past owing to the general reduction in corporate business diversification that has taken place during the last decade or so. And perhaps reflecting this development, the average longer‐run shareholder returns from spinoffs have actually turned negative during the past five years, while the dispersion of spinoff returns has increased, representing greater downside risk for restructurings undertaken without an effective strategy and rationale for increasing efficiency and value.Nonetheless, more than half of all spinoffs over the past five years have generated share price outperformance despite the overall decline in spinoff performance. The authors devote the second half of the article to identifying several key characteristics of the post‐separation entities that indicate the potential for such a restructuring to deliver share price outperformance. The main attributes of value‐increasing spinoffs are size and organic growth, and increases in business focus and capital efficiency; but such transactions have also produced companies that maintain the financial flexibility to pursue M&A along with a dividend policy that is both attractive and sustainable.
Statement of the Financial Economists Roundtable: Corporate Tax Reform
Authors: Boot Arnoud , Logue Dennis , Spatt Chester 
Published: October 2017

Corporate tax reform has been a controversial issue in the U.S. for several years, particularly as U.S. companies have accumulated cash in lower‐tax overseas subsidiaries, while some have used “inversions” to establish overseas corporate domiciles. Two features of U.S. corporate taxation stand out:1. U.S. corporate income tax rates are the highest in the industrialized world. The federal rate is 35%; and, when combined with state taxes, it averages 39%, as compared to an OECD average of 24%.2. U.S. corporations pay U.S. tax on their worldwide income, but can choose to avoid indefinitely corporate tax on foreign profits by not repatriating them. Neither feature is present in most other Western countries, where the norm is a “territorial” system that taxes companies only on their domestic profits.The Trump administration has proposed to cut U.S. corporate tax rates to 20%, thereby bringing them down to the OECD average, and to adopt a territorial tax regime like those found in most other Western nations.In this statement signed by 31 senior financial economists, the authors recommend cutting U.S. corporate tax rates, but retaining the current system of taxing the worldwide profits of U.S. companies (while giving them credit for taxes paid in overseas jurisdictions). Once U.S. rates drop to the international average, the economists point out, U.S. companies would have much less incentive under the worldwide system to use transfer pricing schemes to shift their profits to low‐tax jurisdictions than under the proposed territorial alternative. Indeed, under the current system, if the lower rates under consideration are enacted, the location of a company's business activity (including the firm's underlying intellectual property) would not affect its taxation.Along with lower corporate tax rates, the economists also recommend that Congress limit or remove the corporate option to defer the taxation of offshore profits and provide a schedule for repatriating off‐shore funds, using the inducement of the now lower rates as well as the possibility of a “tax holiday.”
Valuation of a Pharmaceutical Licensing Contract
Authors: Lynch John , Shockley Richard 
Published: October 2017

It is quite common for boutique pharma companies, biotech firms, and university labs to license their intellectual property (a new compound) to large pharmaceutical companies. In such cases, the big pharma companies finance and manage the R&D process and, if successful, market the drugs. In exchange for use of their intellectual property, the outlicensing organizations receive licensing contracts that promise some combination of fixed payments, event‐specific milestone payments, and revenue‐ or profit‐based royalties.The authors show how to estimate the expected present value of the future cash flows promised by such licensing deals. The complicating factor in such valuations is that the licensing contracts are essentially derivative contracts written on drugs in development, which as the authors showed in a paper published in this journal a year ago, are themselves compound options on marketed drugs. The authors use the valuation example from the earlier paper, along with a proposed licensing deal, and walk the reader through the process of valuing the licensing deal's cash flows.
Plasticity and cross‐tolerance to heterogeneous environments: divergent stress responses co‐evolved in an African fruit fly
Authors: Gotcha N. , Terblanche J. S. , Nyamukondiwa C. 
Published: October 2017

AbstractPlastic adjustments of physiological tolerance to a particular stressor can result in fitness benefits for resistance that might manifest not only in that same environment but also be advantageous when faced with alternative environmental stressors, a phenomenon termed ‘cross‐tolerance’. The nature and magnitude of cross‐tolerance responses can provide important insights into the underlying genetic architecture, potential constraints on or versatility of an organism's stress responses. In this study, we tested for cross‐tolerance to a suite of abiotic factors that likely contribute to setting insect population dynamics and geographic range limits: heat, cold, desiccation and starvation resistance in adult Ceratitis rosa following acclimation to all these isolated individual conditions prior to stress assays. Traits of stress resistance scored included critical thermal (activity) limits, chill coma recovery time (CCRT), heat knockdown time (HKDT), desiccation and starvation resistance. In agreement with other studies, we found that acclimation to one stress typically increased resistance for that same stress experienced later in life. A more novel outcome, however, is that here we also found substantial evidence for cross‐tolerance. For example, we found an improvement in heat tolerance (critical thermal maxima, CTmax) following starvation or desiccation hardening and improved desiccation resistance following cold acclimation, indicating pronounced cross‐tolerance to these environmental stressors for the traits examined. We also found that two different traits of the same stress resistance differed in their responsiveness to the same stress conditions (e.g. HKDT was less cross‐resistant than CTmax). The results of this study have two major implications that are of broader importance: (i) that these traits likely co‐evolved to cope with diverse or simultaneous stressors, and (ii) that a set of common underlying physiological mechanisms might exist between apparently divergent stress responses in this species. This species may prove to be a valuable model for future work on the evolutionary and mechanistic basis of cross‐tolerance.
Pulse oximetry values of neonates admitted for care and receiving routine oxygen therapy at a resource‐limited hospital in Kenya
Authors: Morgan Melissa C , Maina Beth , Waiyego Mary , Mutinda Catherine , Aluvaala Jalemba , Maina Michuki , English Mike 
Published: October 2017

AimThere are 2.7 million neonatal deaths annually, 75% of which occur in sub‐Saharan Africa and South Asia. Effective treatment of hypoxaemia through tailored oxygen therapy could reduce neonatal mortality and prevent oxygen toxicity.MethodsWe undertook a two‐part prospective study of neonates admitted to a neonatal unit in Nairobi, Kenya, between January and December 2015. We determined the prevalence of hypoxaemia and explored associations of clinical risk factors and signs of respiratory distress with hypoxaemia and mortality. After staff training on oxygen saturation (SpO2) target ranges, we enrolled a consecutive sample of neonates admitted for oxygen and measured SpO2 at 0, 6, 12, 18 and 24 h post‐admission. We estimated the proportion of neonates outside the target range (≥34 weeks: ≥92%; <34 weeks: 89–93%) with 95% confidence intervals (CIs).ResultsA total of 477 neonates were enrolled. Prevalence of hypoxaemia was 29.2%. Retractions (odds ratio (OR) 2.83, 95% CI 1.47–5.47), nasal flaring (OR 2.68, 95% CI 1.51–4.75), and grunting (OR 2.47, 95% CI 1.27–4.80) were significantly associated with hypoxaemia. Nasal flaring (OR 2.85, 95% CI 1.25–6.54), and hypoxaemia (OR 3.06, 95% CI 1.54–6.07) were significantly associated with mortality; 64% of neonates receiving oxygen were out of range at ≥2 time points and 43% at ≥3 time points.ConclusionThere is a high prevalence of hypoxaemia at admission and a strong association between hypoxaemia and mortality in this Kenyan neonatal unit. Many neonates had out of range SpO2 values while receiving oxygen. Further research is needed to test strategies aimed at improving the accuracy of oxygen provision in low‐resource settings.
Readiness for transition from pediatric to adult care for adolescents with chronic heart disease
Authors: Ekim Ayfer , Kolay Melek , Ocakci Ayse Ferda 
Published: October 2017

AbstractPurposeThe purpose of this study was to determine transition readiness of adolescents with chronic heart disease to adult care.MethodsThe sample of the study comprised 113 adolescents between the ages 12 and 18 years with chronic heart disease. Transition readiness was assessed by the Transition‐Q self‐administered tool.ResultsThe Transition‐Q mean score was 63.0 (range = 31–92). The self‐management skills of the adolescents increased significantly in direct proportion to their ages. Most of the adolescents had a lack of confidence about medication management and communicating with healthcare providers. No significant difference was detected between boys and girls in terms of total and individual items’ scores.Practice ImplicationsTransition readiness should be assessed to understand transitional requirements of adolescents with chronic heart disease and to plan appropriate nursing interventions accordingly.
Alpha‐enolase regulates hepatitis B virus replication through suppression of the interferon signalling pathway
Authors: Xiang‐Chun D. , Xiao‐qing Y. , Ting‐Ting Y. , Zhen‐Hui L. , Xiao‐Yan L. , Xia L. , Yan‐Chao H. , Yi‐Xuan Y. , Li‐Na M. 
Published: October 2017

SummaryPersistent chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of HBV‐related diseases. The molecular mechanisms that underlie HBV infection and associated carcinogenesis are not fully understood. The aim of this study was to explore the role of ENO1 in HBV replication processes. Here, we examined ENO1 expression levels in HBV‐infected and non‐HBV‐infected liver tissues and cells by Western blot analysis, real‐time PCR and immunohistochemistry. In addition, HBsAg and HBeAg in the media of transfected HepG2.2.15 cells were detected using an electrochemical luminescence analyser within 48 hours after ENO1‐specific siRNA transfection. The expression levels of HBV DNA, type I interferon and 5 downstream IFN‐stimulated genes in HepG2.2.15 cells were examined using real‐time PCR. We found ENO1 expression was upregulated in the HBV‐infected liver tissues and cells. Silencing of ENO1 resulted in a significant reduction in HBV replication, and this siRNA‐mediated reaction also caused the upregulation of expression of type I interferon and downstream IFN‐stimulated genes. Therefore, we come to the conclusion ENO1 is involved in HBV replication. It is therefore likely that HBV replication is enhanced following suppression of the IFN signalling pathway. However, the mechanisms that underpin ENO1‐mediated modulation of the IFN signalling pathway remain to be elucidated.
Interpretation of liver stiffness measurement‐based approach for the monitoring of hepatitis B patients with antiviral therapy: A 2‐year prospective study
Authors: Liang X. , Xie Q. , Tan D. , Ning Q. , Niu J. , Bai X. , Chen S. , Cheng J. , Yu Y. , Wang H. , Xu M. , Shi G. , Wan M. , Chen X. , Tang H. , Sheng J. , Dou X. , Shi J. , Ren H. , Wang M. , Zhang H. , Gao Z. , Chen C. , Ma H. , Chen Y. , Fan R. , Sun J. , Jia J. , Hou J. 
Published: October 2017

SummaryLiver biopsy is not routinely performed in treated chronic hepatitis B. Liver stiffness measurement has been validated for noninvasive liver fibrosis assessment in pretreatment chronic hepatitis B but has not been assessed for fibrosis monitoring during antiviral therapy. Liver stiffness was systemically monitored by Fibroscan® every 6 months in a cohort of patients with hepatitis B receiving antiviral therapy and compared with liver biopsies at baseline and week 104. A total of 534 hepatitis B e antigen‐positive treatment‐naive patients receiving telbivudine‐based therapy with qualified liver stiffness measurement at baseline and week 104 were analyzed, 164 of which had adequate paired liver biopsies. Liver stiffness decreased rapidly (−2.2 kPa/24 weeks) in parallel with alanine aminotransferase (ALT) from 8.6 (2.6‐49.5) kPa at baseline to 6.1 (2.2‐37.4) kPa at week 24. Interestingly, liver stiffness decreased slowly (−0.3 kPa/24 weeks) but continually from week 24 to week 104 (6.1 vs 5.3 kPa, P < .001) while ALT levels remained stable within the normal range. More importantly, liver stiffness declined significantly irrespective of baseline ALT levels and liver necroinflammation grades. From baseline to week 104, the proportion of patients with no or mild fibrosis (Ishak, 0‐2) increased from 74.4% (122/164) to 93.9% (154/164). Multivariate analysis revealed that percentage decline of 52‐week liver stiffness from baseline was independently associated with 104‐week liver fibrosis regression (odds ratio, 3.742; P = .016). Early decline of 52‐week liver stiffness from baseline may reflect the remission of both liver inflammation and fibrosis and was predictive of 104‐week fibrosis regression in treated patients with chronic hepatitis B.
Risk of diabetes in viral hepatitis B or C patients compared to that in noninfected individuals in Korea, 2002‐2013: A population‐based cohort study
Authors: Choi H. Y. , Kim Y. , Cho H. , Kim B. H. , Ki M. 
Published: October 2017

SummaryWhile the association between hepatitis C virus (HCV) infection and diabetes has been established, the relationship between hepatitis B virus (HBV) infection and diabetes remains unclear. Therefore, we compared the association between diabetes development in HBV, HCV and co‐infected (HBV/HCV) patients to that in noninfected participants using population‐based cohort data. We used the National Health Insurance Service‐National Sample Cohort, which consists of 514 791 randomly selected persons among those who underwent health check‐ups from 2002 to 2003 aged 40‐79 years. Adults found to have HBV or HCV infection from 2002 to 2003, without a prior history of diabetes, were selected as subjects. Competing risk regression models were used to estimate cumulative incidence and hazards ratios (HRs) of diabetes development. The cumulative incidences, incidence densities and HRs of diabetes were highest in the co‐infected group, followed by those in the HCV‐, HBV‐ and noninfected groups. The 12‐year cumulative incidences were as follows: 42.0% in HBV/HCV‐, 32.9% in HCV‐, 23.9% in HBV‐ and 18.3% in the noninfected groups. The incidence density per 1000 person‐years was 55.0, 51.5, 38.2 and 28.2 for the HBV/HCV‐, HCV‐, HBV‐ and noninfected groups, respectively. The adjusted HRs for diabetes were 1.90, 1.68 and 1.41 for the HBV/HCV‐, HCV‐ and HBV‐infected groups, respectively. Our findings suggest that both HCV and HBV infections are associated with the development of diabetes; therefore, prevention of, screening for, and treatment of both may reduce the risk of diabetes in these patients.
Role of Functional IFNL4,IFNLR1,IFNA, IFNAR2 Polymorphisms in Hepatitis B virus‐related liver disease in Han Chinese population
Authors: Ma N. , Zhang X. , Yang L. , Zhou J. , Liu W. , Gao X. , Yu F. , Zheng W. , Ding S. , Gao P. , Yuan M. , Liu D. 
Published: October 2017

SummaryRecent studies show that variants in some interferon genes together with interferon receptor genes are associated with the outcome of infectious diseases. We examined the association between the risk of hepatitis B virus (HBV)‐related liver disease and the functional polymorphisms within IFNL4, IFNLR1, IFNA1, IFNA2, IFNA5 and IFNAR2 genes (14 loci in all) in a Han Chinese population. A total of 3128 people participated and were divided into 5 groups: healthy controls, natural clearance, chronic hepatitis B(CHB), liver cirrhosis and hepatocellular carcinoma (HCC). Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with HBV infection, and IFNLR1‐rs4649203 was associated with HBV recovery. Moreover, we demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with HCC. Three SNPs in IFNL4 gene may be important susceptible factors for the progression of HBV‐related liver disease by trend chi‐square test. The IFNL4 haplotype conformed by rs12971396_G, rs8113007_T and rs7248668A was more frequent in HCC than CHB and LC group. Three polymorphisms in the 5′ region of the IFNL4 gene are associated with the progression of HBV‐related liver disease. IFNA1‐ rs1831583 and IFNA2‐ rs649053 are associated with the development of HCC. IFNLR1‐ rs4649203, rs7525481 are predictors for HBV infection, and rs4649203 is a predictor of spontaneous clearance. IFNAR2 ‐rs1051393, rs12233338 may be predictive markers of HBV infection in the Chinese population.
Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin
Authors: Henry C.J. , Flesner B.K. , Bechtel S.A. , Bryan J.N. , Tate D.J. , Selting K.A. , Lattimer J.C. , Bryan M.E. , Grubb L. , Hausheer F. 
Published: October 2017

BackgroundTransitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans.Hypothesis/ObjectivesWe hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept.AnimalsFourteen client‐owned dogs were prospectively enrolled.MethodsTumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia.ResultsA 90‐minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P= 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days).Conclusions and Clinical ImportanceTavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.
Plumbagin‐mediating GLUT1 suppresses the growth of human tongue squamous cell carcinoma
Authors: Na S , Zhang J , Zhou X , Tang A , Huang D , Xu Q , Xue D , Qiu J 
Published: October 2017

ObjectiveThe purpose of this study was to investigate the clinical and histopathological characteristics of GLUT1 in human tongue squamous cell carcinoma (TSCC) and the role of plumbagin (PLB)‐mediating GLUT1 in the growth of TSCC.Subjects and methodsForty‐five cases of TSCC samples were collected and the expression and location of GLUT1 was analyzed. The role and mechanism of PLB meditating GLUT1 in the inhibitory growth of human TSCC cell line CAL27 were investigated in vitro and vivo.ResultsThe expression of GLUT1 was observed in all samples of human TSCC by immunohistochemical staining. GLUT1 expression was significantly correlated with lymph node metastasis and clinical stage in TSCC. PLB treatment decreased cell viability and colony formation, and increased cell apoptosis in association with the downregulation of GLUT1 via inhibiting PI3K/Akt pathway in vitro and PLB suppressed tumor growth in correlation with downregulation of GLUT1, compared with control group in vivo.ConclusionsThe findings demonstrated a novel anti‐cancer mechanism of PLB, inhibitory TSCC growth via suppressing PI3K/Akt/GLUT1 pathway, which will supply a theoretical basis for PLB to treat TSCC.