909 research outputs found
How do banks assess entrepreneurial competence? The role of voluntary information disclosure
This research adds to the literature on relationship lending in the small business context by discussing the roles of entrepreneurial competence and voluntarily disclosed information as determinants of credit access. More specifically, we propose that the loan managerâs evaluation of the information voluntarily disclosed by the entrepreneur is an important complement to publicly available financial data and soft information collected through observation and third parties in framing the loan managerâs perception of the entrepreneurâs competence. Further, we argue that banks charge lower interest rates if the loan manager perceives the entrepreneur to be competent. Econometric analysis based on 433 bank-firm relationships supports these hypothesised relationships. The results imply that entrepreneurs need to communicate their competence effectively to loan managers, and that banks should utilise their loan managersâ personal evaluations as inputs to lending decisions
Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach
Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in â„ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered
An evolutionary stage model of outsourcing and competence destruction : a Triad comparison of the consumer electronics industry
Outsourcing has gained much prominence in managerial practice and academic discussions in the last two decades or so. Yet, we still do not understand the full implications of outsourcing strategy for corporate performance. Traditionally outsourcing across borders is explained as a cost-cutting exercise, but more recently the core competency argument states that outsourcing also leads to an increased focus, thereby improving effectiveness. However, no general explanation has so far been provided for how outsourcing could lead to deterioration in a firmâs competence base. We longitudinally analyze three cases of major consumer electronics manufacturers, Emerson Radio from the U.S., Japanâs Sony and Philips from the Netherlands to understand the dynamic process related to their sourcing strategies. We develop an evolutionary stage model that relates outsourcing to competence development inside the firm and shows that a vicious cycle may emerge. Thus it is appropriate to look not only at how outsourcing is influenced by an organizationâs current set of competences, but also how it alters that set over time. The four stages of the model are offshore sourcing, phasing out, increasing dependence on foreign suppliers, and finally industry exit or outsourcing reduction. The evolutionary stage model helps managers understand for which activities and under which conditions outsourcing across borders is not a viable option.
Results suggest that each of these firms had faced a loss of manufacturing competitiveness in its home country, to which it responded by offshoring and then outsourcing production. When a loss of competences occurred, some outsourcing decisions were reversed
Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors
INTRODUCTION: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors.
BACKGROUND:
METHODS: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simonâs Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety.
RESULTS:
46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event.
CONCLUSIONS: Treatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25
Family history of cancer and the risk of childhood brain tumors: a pooled analysis of the ESCALE and ESTELLE studies (SFCE)
PURPOSE: Although some specific genetic syndromes such as neurofibromatosis (NF) have been identified as risk factor of childhood brain tumors (CBT), the potential role of inherited susceptibility in CBT has yet to be elucidated.
METHODS: To further investigate this, we conducted a pooled analysis of two nationwide case-control studies ESCALE and ESTELLE. The mothers of 509 CBT cases and 3,102 controls aged under 15Â years who resided in France at diagnosis/interview, frequency-matched by age and gender, responded to a telephone interview conducted by trained interviewers. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression.
RESULTS: CBT was significantly associated with the family history of cancer in relatives (OR 1.2, 95% CI 1.0-1.5). The OR was slightly higher for maternal relatives than for paternal relatives, and when at least two relatives had a history of cancer. CBT was significantly associated with a family history of brain tumor (OR 2.1, 95% CI 1.3-3.7). This association seemed stronger for first-degree relatives (mother, father, and siblings), for whom, by contrast, no association was seen for cancers other than CBT. No specificity by CBT subtypes or by age of the children were found for any of these findings.
CONCLUSION: Our findings support the hypothesis of a familial susceptibility of CBT, not due to being a known NF carrier
Towards a strategic understanding of global teams and their HR implications : an expert dialogue
Drawing on initial insights emerging from a panel at the EIBA 2016 Conference in Vienna, here discussants and expert panelists engage in a follow-on conversation on the HRM implications of global teams for international organizations. First we set out how HRM can enable global teams and their constituent members to overcome the new and considerable challenges of global teams. These challenges span levels of analysis, time and space. Next we debate global teams as a strategic response to the dual pressures of global integration and local adaptation. We consider what HRM is needed for global teams to successfully resolve this dilemma, challenging practitioners to move beyond the âbest practicesâ and âalignmentâ dichotomy. Lastly we look to the future to consider implications for research. We propose a rich research agenda focused on the complexities of the global team context
Dynamic factor model with infinite-dimensional factor space:forecasting
The paper compares the pseudo real-time forecasting performance of three Dynamic Factor Models: (i) The standard principal-component model introduced by Stock and Watson in 2002, (ii) The model based on generalized principal components, introduced by Forni, Hallin, Lippi and Reichlin in 2005, (iii) The model recently proposed by Forni, Hallin, Lippi and Zaffaroni in 2015. We employ a large monthly dataset of macroeconomic and financial time series for the U.S. economy, which includes the Great Moderation, the Great Recession and the subsequent recovery (an update of the so-called Stock and Watson dataset). Using a rolling window for estimation and prediction, we find that (iii) significantly outperforms (i) and (ii) in the Great Moderation period for both Industrial Production and Inflation, that (iii) is also the best method for Inflation over the full sample. However, (iii) is outperformed by (ii) and (i) over the full sample for Industrial Production
Outcome of children and adolescents with central nervous system tumors in phase I trials
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors agedâ<â18Â years at enrollment in their first dose-finding trial between 2000 and 2014Â at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses. Overall, 114 patients were included (109 evaluable for efficacy). Median age was 10.2Â years (range 1.0-17.9). Main diagnoses included: medulloblastoma/primitive neuroectodermal tumors (32.5%) and high-grade gliomas (23.7%). Complete/partial responses (CR/PR) were reported in 7.3% patients and stable disease (SD) in 23.9%. Performance status of 90-100%, school/work attendance, normal ALT/AST and CR/PR/SD correlated with better overall survival (OS) in the univariate analysis. No variables assessable at screening/enrollment were associated with OS in the multivariate analysis. Five patients (4.5%) were discontinued from study due to toxicity. No toxic deaths occurred. Median OS was 11.9Â months with CR/PR, 14.5Â months with SD and 3.7Â months with progressive disease (pâ<â0.001). The enrollment of children and adolescents with CNS tumors in phase I trials is feasible, safe and offers potential benefit for the patients. Sustained disease stabilization has a promising role as a marker of anti-tumor activity in children with CNS tumors participating in phase I trials
Forecasting with Big Data: A Review
Big Data is a revolutionary phenomenon which is one of the most frequently discussed topics in the modern age, and is expected to remain so in the foreseeable future. In this paper we present a comprehensive review on the use of Big Data for forecasting by identifying and reviewing the problems, potential, challenges and most importantly the related applications. Skills, hardware and software, algorithm architecture, statistical significance, the signal to noise ratio and the nature of Big Data itself are identified as the major challenges which are hindering the process of obtaining meaningful forecasts from Big Data. The review finds that at present, the fields of Economics, Energy and Population Dynamics have been the major exploiters of Big Data forecasting whilst Factor models, Bayesian models and Neural Networks are the most common tools adopted for forecasting with Big Data
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