Balancing artistic and financial performance: is collaborative governance the answer?

Purpose: Opera houses have been traditionally publicly financed in many western countries. However, today many opera houses are facing serious financial troubles, due to the recent financial crisis. There is thus a widespread public debate on measures to ensure agency efficiency for performing arts organizations. Focusing on the reform implemented recently in Italy, which submitted opera houses that had severe financial difficulties to a recovery plan and encouraged forms of collaborative governance (CG), the purpose of this paper is to investigate the impact of CG on the performance of the arts sector. Design/methodology/approach: Multiple case studies are used, on longitudinal data from multiple sources over a period of up to five years, in order to triangulate the narrative of financial and artistic performance and ensure trustworthiness. The study thus spans the period before the Bray Law came into force (2013) and covers the entire period in which recovery plans were implemented. Findings: The analysis explores how opera houses are building sustainability for themselves and the community in terms of financial and artistic performance through CG. Various forms of CG adopted yielded positive results. Furthermore, more robust forms of CG generated better performance, especially from a financial point of view. Originality/value: This paper adds to the limited knowledge of CG in the non-profit sector by bridging the fields of agency performance and CG. It discusses how the introduction of forms of CG can build up long-term sustainability, solving the dilemma of how to achieve financial equilibrium without compromising artistic quality, focusing on the case of opera houses, which are notably affected by Baumol’s cost disease

Monitoraggio ambientale e biologico dell’esposizione ad idrocarburi mono-aromatici ed a metil tert-butil etere in un gruppo di lavoratori addetti all’erogazione di carburanti

Lo studio è stato condotto per valutare gli indicatori biologici di esposizione a vapori di benzina in lavoratori addetti all’erogazione di carburante tramite un approccio combinato di monitoraggio ambientale e biologico. L’esposizione personale a benzene, toluene, etilbenzene e xilene (BTEX) e l’escrezione urinaria di BTEX, metil tert-butil etere (MTBE-U), degli acidi trans,transmuconico (t,t-MA) ed S-fenilmercapturico (S-PMA) e della cotinina sono stati valutati con tecniche cromatografiche accoppiate alla spettrometria di massa. I livelli di MTBE-U erano influenzati dalla sola esposizione professionale a vapori di benzina, mentre quelli di B-U ed S-PMA dipendevano da abitudine tabagica ed esposizione professionale

Combination of ultrasound and molecular testing in malignancy risk estimate of Bethesda category IV thyroid nodules: results from a single-institution prospective study

Purpose: Malignancy prediction in indeterminate thyroid nodules is still challenging. We prospectively evaluated whether the combination of ultrasound (US) risk stratification and molecular testing improves the assessment of malignancy risk in Bethesda Category IV thyroid nodules. Methods: Ninety-one consecutively diagnosed Bethesda Category IV thyroid nodules were prospectively evaluated before surgery by both ACR- and EU-TIRADS US risk-stratification systems and by a further US-guided fine-needle aspiration cytology (FNAC) for the following molecular testing: BRAFV600E, N-RAS codons 12/13, N-RAS codon 61, H-RAS codons 12/13, H-RAS codon 61, K-RAS codons 12/13, and K-RAS codon 61 point-mutations, as well as PAX8/PPARγ, RET/PC1, and RET/PTC 3 rearrangements. Results: At histology, 37% of nodules were malignant. No significant association was found between malignancy and either EU- or ACR-TIRADS. In total, 58 somatic mutations were identified, including 3 BRAFV600E (5%), 5 N-RAS 12/13 (9%), 13 N-RAS 61 (22%), 7 H-RAS 12/13 (12%), 11 H-RAS 61 (19%), 6 K-RAS 12/13 (10%), 8 K-RAS 61 (14%) mutations and 2 RET/PTC1 (4%), 0 RET/PTC 3 (0%), 3 PAX8/PPARγ (5%) rearrangements. At least one somatic mutation was found in 28% and 44% of benign and malignant nodules, respectively, although malignancy was not statistically associated with the outcome of the mutational test. However, the combination of ACR-, but not EU-, TIRADS with the presence of at least one somatic mutation, was significantly associated with malignant histology (P = 0.03). Conclusion: US risk stratification and FNAC molecular testing may synergistically contribute to improve malignancy risk estimate of Bethesda category IV thyroid nodules

Patterns of novel alleles and genotype/phenotype correlations resulting from the analysis of 108 previously undetected mutations in patients affected by neurofibromatosis type I

Neurofibromatosis type I, a genetic disorder due to mutations in the NF1 gene, is characterized by a high mutation rate (about 50% of the cases are de novo) but, with the exception of whole gene deletions associated with a more severe phenotype, no specific hotspots and few solid genotype/phenotype correlations. After retrospectively re-evaluating all NF1 gene variants found in the diagnostic activity, we studied 108 patients affected by neurofibromatosis type I who harbored mutations that had not been previously reported in the international databases, with the aim of analyzing their type and distribution along the gene and of correlating them with the phenotypic features of the affected patients. Out of the 108 previously unreported variants, 14 were inherited by one of the affected parents and 94 were de novo. Twenty-nine (26.9%) mutations were of uncertain significance, whereas 79 (73.2%) were predicted as pathogenic or probably pathogenic. No differential distribution in the exons or in the protein domains was observed and no statistically significant genotype/phenotype correlation was found, confirming previous evidences

Biomarkers of nucleic acid oxidation, polymorphism in, and expression of, hOGG1 gene in styrene-exposed workers.

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Monitoraggio biologico ed esposizione a silice: applicazione di nuovi indicatori di dose e di effetto

In 16 addetti alla produzione di marmi ricomposti è stato misurato Si-CAE, è stata eseguita una spirometria e sono stati dosati 8oxoGua, 8oxoGuo, 8oxodGuo, SP-A, SP-D, CC16 e HO-1. Si sono osservati valori spirometrici (FVC e FEV1) più bassi nei lavoratori rispetto ai controlli. Nei lavoratori abbiamo osservato livelli più elevati dei seguenti marcatori: Si-CAE, 8oxoGuo ed espressione di HO-1. Lo studio evidenzia che l’esposizione a silice può aumentare i livelli di Si-CAE, che può essere usato per stimare la dose al bersaglio. Infine si evidenziavano aspecifiche alterazioni spirometriche ed un aumento di biomarcatori d’effetto

Monitoring cfDNA in plasma and in other liquid biopsies of advanced EGFR mutated NSCLC patients: A pilot study and a review of the literature

In order to study alternatives at the tissue biopsy to study EGFR status in NSCLC patients, we evaluated three different liquid biopsy platforms (plasma, urine and exhaled breath condensate, EBC). We also reviewed the literature of the cfDNA biological sources other than plasma and compared our results with it about the sensitivity to EGFR mutation determination. Twenty-two EGFR T790M-mutated NSCLC patients in progression to first-line treatment were enrolled and candidate to osimertinib. Plasma, urine and EBC samples were collected at baseline and every two months until progression. Molecular analysis of cfDNA was performed by ddPCR and compared to tissue results. At progression NGS analysis was performed. The EGFR activating mutation detection reached a sensitivity of 58 and 11% and for the T790M mutation of 45 and 10%, in plasma and urine samples, respectively. Any DNA content was recovered from EBC samples. Considering the plasma monitoring study, the worst survival was associated with positive shedding status; both plasma and urine molecular progression anticipated the radiological worsening. Our results confirmed the role of plasma liquid biopsy in testing EGFR mutational status, but unfortunately, did not evidence any improvement from the combination with alternative sources, as urine and EBC

Alzheimer\u27s Therapeutics Targeting Amyloid Beta 1–42 Oligomers II: Sigma-2/PGRMC1 Receptors Mediate Abeta 42 Oligomer Binding and Synaptotoxicity

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer\u27s disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer\u27s disease patients\u27 brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of Abeta oligomers in AD and is a tractable target for small molecule disease-modifying therapeutics

Rehabilitation of memory following brain injury (ReMemBrIn): study protocol for a randomised controlled trial

Background Impairments of memory are commonly reported by people with traumatic brain injuries (TBI). Such deficits are persistent, debilitating, and can severely impact quality of life. Currently, many do not routinely receive follow-up appointments for residual memory problems following discharge. Methods/Design This is a multi-centre, randomised controlled trial investigating the clinical and cost-effectiveness of a group-based memory rehabilitation programme. Three hundred and twelve people with a traumatic brain injury will be randomised from four centres. Participants will be eligible if they had a traumatic brain injury more than 3 months prior to recruitment, have memory problems, are 18 to 69 years of age, are able to travel to one of our centres and attend group sessions, and are able to give informed consent. Participants will be randomised in clusters of 4 to 6 to the group rehabilitation intervention or to usual care. Intervention groups will receive 10 weekly sessions of a manualised memory rehabilitation programme, which has been developed in previous pilot studies. The intervention will include restitution strategies to retrain impaired memory functions and compensation strategies to enable participants to cope with their memory problems. All participants will receive a follow-up postal questionnaire and an assessment by a research assistant at 6 and 12 months post-randomisation. The primary outcome is the Everyday Memory Questionnaire at 6 months. Secondary outcomes include the Rivermead Behavioural Memory Test-3, General Health Questionnaire-30, health related quality of life, cost-effectiveness analysis determined by the EQ-5D and a service use questionnaire, individual goal attainment, European Brain Injury Questionnaire (patient and relative versions), and the Everyday Memory Questionnaire-relative version. The primary analysis will be based on intention to treat. A mixed-model regression analysis of the Everyday Memory Questionnaire at 6 months will be used to estimate the effect of the group memory rehabilitation programme. Discussion The study will hopefully provide robust evidence regarding the clinical and cost-effectiveness of a group-based memory rehabilitation intervention for civilians and military personnel following TBI. We discuss our decision-making regarding choice of outcome measures and control group, and the unique challenges to recruiting people with memory problems to trials