A reconceptualization of fear of failure in entrepreneurship

Fear of failure both inhibits and motivates entrepreneurial behavior and therefore represents a rich opportunity for better understanding entrepreneurial motivation. Although considerable attention has been given to the study of fear of failure in entrepreneurship, scholars in this field have investigated this construct from distinct disciplinary perspectives. These perspectives use definitions and measures of fear of failure that are potentially in conflict and are characterized by a static approach, thereby limiting the validity of existing findings about the relationship between fear of failure and entrepreneurship. The purpose of this paper is to delineate more precisely the nature of fear of failure within the entrepreneurial setting. Using an exploratory and inductive qualitative research design, we frame this construct in terms of socially situated cognition by adopting an approach that captures a combination of cognition, affect and action as it relates to the challenging, uncertain, and risk-laden experience of entrepreneurship. In so doing, we provide a unified perspective of fear of failure in entrepreneurship in order to facilitate progress in understanding its impact on entrepreneurial action and outcomes

Liquid biopsy in clear cell renal cell carcinoma. Urinary miR-210-3p as emerging specific biomarker

Themost common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC) that accounts for 70–80% of all renal malignancies. To date, no useful markers are available in clinical practice for early diagnosis and for optimal patient stratification. MicroRNAs, a class of small non-coding RNA, are emerging as promising molecules in the management of urological tumors suggesting the possibility of using them as non-invasive biomarkers. The aim of this study is to evaluate whether miR-210-3p may be an accurate non invasive diagnostic and prognostic biomarker for ccRCC patients

Perifosine as a Potential Novel Anti-Cancer Agent Inhibits EGFR/MET-AKT Axis in Malignant Pleural Mesothelioma

PI3K/AKT signalling pathway is aberrantly active and plays a critical role for cell cycle progression of human malignant pleural mesothelioma (MMe) cells. AKT is one of the important cellular targets of perifosine, a novel bio-available alkylphospholipid that has displayed significant anti-proliferative activity in vitro and in vivo in several human tumour model systems and is currently being tested in clinical trials.We tested Perifosine activity on human mesothelial cells and different mesothelioma cell lines, in order to provide evidence of its efficacy as single agent and combined therapy.We demonstrate here that perifosine, currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials, caused a dose-dependent reduction of AKT activation, at concentrations causing MMe cell growth arrest. In this study we firstly describe that MMe cells express aside from AKT1 also AKT3 and that either the myristoylated, constitutively active, forms of the two proteins, abrogated perifosine-mediated cell growth inhibition. Moreover, we describe here a novel mechanism of perifosine that interferes, upstream of AKT, affecting EGFR and MET phosphorylation. Finally, we demonstrate a significant increase in cell toxicity when MMe cells were treated with perifosine in combination with cisplatin.This study provides a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe

Smoking influence in Takotsubo syndrome: insights from an international cohort

Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS).Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted.Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 +/- 11 vs. 72 +/- 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97).Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry

Background and aims: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. Methods: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. Results: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality. Conclusions: Statin therapy after a TTS event was not associated with better prognosis at follow-up

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry

Background: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. Methods and results: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). Conclusions: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS

Pleural mesothelioma in a nine-month-old dog

This paper reports on an unusual case of pleural epitheloid mesothelioma in a nine-month-old male, mixed breed dog. The dog was presented in-extremis and, on post mortem examination, multiple, exophytic, frequently pedunculated, yellowish-red, soft to firm masses ranging from 3 mm to 6 cm in diameter were diffusely distributed over, and attached to, the pericardial and parietal pleural surfaces. Microscopically, these masses consisted of round to partially polygonalshaped, anaplastic cells with minimal cytoplasm and hyperchromatic nuclei covering papillomatous projections or as part of more densely cellular masses. A supporting fibrovascular stroma and mitotic figures were also evident. Constituent tumour cells were labeled positively with antibodies against both vimentin and cytokeratin. In contrast, the same cells exhibited equivocal labeling with an antibody directed against calretinin antigen and did not label with antibodies against carcinoembryonic antigen (CEA) and milk fat globule-related antigen (MFGRA). Such tumours are rare in dogs, particularly in such a young animal

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes

Background: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. Methods and results: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). Conclusions: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed

Impact of intra-aortic balloon counterpulsation on all-cause mortality among patients with Takotsubo syndrome complicated by cardiogenic shock: results from the German-Italian-Spanish (GEIST) registry

Aims: Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction and can be complicated by cardiogenic shock (CS). However, few data are available on optimal care in TTS complicated by CS. Aim of this study was to evaluate short- and long-term impact of intra-aortic balloon pumping (IABP) on mortality in this setting. Methods and results: In a multi-centre, international registry on TTS, 2248 consecutive patients were enrolled from 38 centres from Germany, Italy, and Spain. Of the 2248 patients, 212 (9.4%) experienced CS. Patients with CS had a higher prevalence of diabetes (27% vs. 19%), male sex (25% vs. 10%), and right ventricular involvement (10% vs. 5%) (P < 0.01 in all cases). Forty-three patients with CS (20% of 212) received IABP within 8 h (interquartile range 4-18) after admission. No differences in terms of age, gender, cardiovascular risk factors, and admission left ventricular ejection fraction were found among patients with and without IABP. There were no significant differences in terms of 30-day mortality (16% vs. 17%, P = 0.98), length of hospitalization (18.9 vs. 16.7 days, P = 0.51), and need of invasive ventilation (35% vs. 41%, P = 0.60) among two groups: 30-day survival was not significantly different even after propensity score adjustment (log-rank P = 0.73). At 42-month follow-up, overall mortality in patients with CS and TTS was 35%, not significantly different between patients receiving IABP and not (37% vs. 35%, P = 0.72). Conclusions: In a large multi-centre observational registry, the use of IABP was not associated with lower mortality rates at short- and long-term follow-up in patients with TTS and CS