Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?

[EN] Academic spin-offs (ASOs) help universities transfer knowledge or technology through business projects developed by academic staff. This investigation aims at analyzing the critical factors for spin-off creation at universities operating in crisis-raven, entrepreneurship-unfriendly environments. Such factors revolve around four types of resources: environmental, institutional, organizational, and personal. Focusing on a Southern European context, as an example of an unfriendly environment affected by economic crisis, an entrepreneurial university (the Technical University of Valencia in Spain, UPV) is our research setting. Through a case study approach, we examine the potential of UPV as a springboard for ASOs. Our results show an adverse local environment, a rather favorable influence of institutional and organizational drivers, and a mixed role of personal factors. Our findings illustrate that UPV consistently supports spin-off creation due to a greater (rather positive) reflexivity from its institutional, organizational and personal resources than the (negative) imprinting of the unfriendly environment. This helps counter-balance the structural unfriendliness for academic entrepreneurship, and trigger a crisis-led risk-taking attitude by academic staff. Hence, UPV should continue with its current strategy of supporting academic entrepreneurship, and might transfer best practices to other universities also affected by unfavorable environmental conditions. Generally speaking, we would advise universities facing adverse circumstances to develop rules and mechanisms for academic entrepreneurship, carefully revise and improve malfunctions, and become involved throughout the whole process of spin-off development. All in all, our study advances understanding of how the different drivers for ASO creation can be revamped by universities located in unfriendly environments, having in mind the key role that universities play in fostering social and economic development through academic entrepreneurship in such environments.The authors would like to thank the Universitat Politecnica de Valencia (grant PAID-06-12-0916), and the Spanish Ministry of Economy and Competitiveness (grant ECO2011-29863), for their financial support for this research.Seguí-Mas, E.; Oltra, V.; Tormo-Carbó, G.; Sarrión Viñes, F. (2017). Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?. International Entrepreneurship and Management Journal. 1-42. doi:10.1007/s11365-017-0478-zS142Acs, Z. J., Audretsch, D. B., & Lehmann, E. E. (2013). The knowledge spillover theory of entrepreneurship. Small Business Economics, 41, 757–774.Alemany, L. (2011). 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Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome.

Two novel mutations of the ribosomal S6 kinase 2 gene (also known as RSK2) have been identified in two unrelated patients with Coffin-Lowry syndrome. The first mutation consists of a de novo insertion of a 5'-truncated LINE-1 element at position -8 of intron 3, which leads to a skipping of exon 4, leading to a shift of the reading frame and a premature stop codon. The L1 fragment (2800 bp) showed a rearrangement with a small deletion, a partial inversion of the ORF 2, flanked by short direct repeats which duplicate the acceptor splice site. However, cDNA analysis of the patient shows that both sites are apparently not functional. The second family showed the nucleotide change 803T>C in exon 10, resulting in the F268S mutation. This mutation was detected in two monozygotic twin patients and in their mother, who was mildly affected. The patients fulfill the clinical criteria of the syndrome, and therefore the mutation provides further support for the importance of phenylalanine at position 268, which is highly conserved in the protein kinase domain of many serine-threonine protein kinases

Visual memory tests enhance the identification of amnestic MCI cases at greater risk of Alzheimer's disease

Objectives: To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer's disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests.Participants: 4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates.Results: All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66-9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC.Conclusions: Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI