Brunello Cucinelli: A Humanistic Approach to Luxury, Philanthropy, and Stewardship

Over the past few decades, the Italian clothier Brunello Cucinelli has created a highly profitable, globally present, luxury fashion line while reading medieval monastics. Entrepreneurs and business ethicists might be intrigued to explore how this apparent paradox is resolved in Cucinelli’s manner of running his company—a practice inspired, in part, by drawing widely from works in the Western humanistic and religious canon. From his study of St. Benedict and St. Francis, among others, Cucinelli has found ways of squaring particularly daunting circles: the correlation between luxury and quality; the meaning of labor for human dignity in an age of excessive production and consumption; the role of philanthropy in tandem with profit-making; and the transfiguration of the corporate CEO into an abstemious and caring abbot. By reading from Cucinelli’s chosen philosophical touchstones, and exploring the effects of that reading on his day-to-day operations, we may glean insight into his particular understanding of luxury as it relates to his “humanistic enterprise” in the world of business, and to the specific demands such an undertaking makes on those who would be its leaders and stewards. The extent to which Cucinelli’s business ethics might be translated beyond his Italian context, and in entrepreneurial initiatives other than high-end fashion, is also considered

A New Philosophy of Clothes: Brunello Cucinelli\u27s Neohumanistic Business Ethics

The Italian entrepreneur Brunello Cucinelli has spent decades building a successful eponymous international clothing brand from the small Umbrian hamlet of Solomeo. What is perhaps less well known is the degree to which his business ethics are informed by the long history of Western humanistic philosophy. Given that Cucinelli recently received an honorary doctorate in Philosophy and the Ethics of Human Relations from the University of Perugia, and around that time saw annual sales exceed two hundred million dollars, there is an increasing mandate to explore whether or to what extent Cucinelli’s investment in the humanistic tradition contributes positively to his success as an entrepreneur. Is philosophy profitable? Do ethical business practices translate into better products, enhanced employee well-being, and greater fiscal returns? Not only is it worth replying to such questions with a narrow focus on Cucinelli’s business, it is of considerable interest how his methodology—including bold philanthropic initiatives based on humanistic principles—may usefully inform the wider dialogue on business ethics, and whether his results can be meaningfully replicated in other locations and types of industry

Teaching without explication: pedagogical lessons from Rancière's The Ignorant Schoolmaster in The Grand Budapest Hotel and The Emperor's Club

How can one teach what one does not know? Most film depictions of teaching follow a satisfying (and it would seem endlessly entertaining) Aristotelian dramatic structure. But what if the teacher does not know what she is summoned to teach? And what if there were a theory of pedagogy that celebrated a teacher's ignorance rather than her authority (power, position, privilege, pre-established role) or expertise (knowledge, experience, judgment)? How or why, in Jacques Rancière’s parlance, an ‘ignorant schoolmaster’ may have a talent for teaching – that is, an efficacy and influence on student learning that trumps antecedent knowledge – becomes a locus of inquiry in these pages. Several of Wes Anderson’s films can be said to include an ignorant schoolmaster, or ‘New Master’. Arguably, The Grand Budapest Hotel (2014) features the highest achievement of expression of the ignorant schoolmaster in Anderson’s work: M. Gustave teaches without knowing, teaches inadvertently as he learns what needs to be taught. By way of contrast – that is, as a way of illuminating M. Gustave’s representative qualities as an ignorant schoolmaster – I will also consider the character of the professional, authoritative, and knowledgeable preparatory school teacher, or 'Old Master', William Hundert in The Emperor's Club (2002)

Dexamethasone Administration During Definitive Radiation and Temozolomide Renders a Poor Prognosis in a Retrospective Analysis of Newly Diagnosed Glioblastoma Patients

BACKGROUND: Dexamethasone (DXM) is commonly used in the management of cerebral edema in patients diagnosed with glioblastoma multiforme (GBM). Bevacizumab (BEV) is FDA-approved for the progression or recurrence of GBM but has not been shown to improve survival when given for newly diagnosed patients concurrently with radiation (RT) and temozolomide (TMZ). Both DXM and BEV reduce cerebral edema, however, DXM has been shown to induce cytokine cascades which could interfere with cytotoxic therapy. We investigated whether DXM would reduce survival of GBM patients in the setting of concurrent TMZ and BEV administration. METHODS: We reviewed the treatment of all 73 patients with GBM who received definitive therapy at our institution from 2005 to 2013 with RT (60 Gy) delivered with concurrent daily TMZ (75 mg/m2). Of these, 34 patients also were treated with concurrent BEV (10 mg/kg every two weeks). Patients received adjuvant therapy (TMZ or TMZ/Bev) until either progression, discontinuation due to toxicity, or 12 months after radiation completion. All patients who had GBM progression with TMZ were offered BEV for salvage therapy, with 19 (56 %) receiving BEV. RESULTS: With a median follow-up of 15.6 months, 67 (91.8 %) patients were deceased. The OS for the entire cohort was 15.9 months, while the PFS was 7.7 months. The extent of resection was a prognostic indicator for OS (p  = .0044). The median survival following gross tumor resection (GTR) was 22.5 months, subtotal resection (STR) was 14.9 months, and biopsy was 12.1 months. The addition of BEV to TMZ with RT was borderline significantly associated with increased PFS (9.4 vs. 5.1 months, p = 0.0574) although was not significantly associated with OS (18.1 vs. 15.3 months respectively, p  = 0.3064). In patients receiving TMZ, DXM use concurrent with RT was a poor prognostic indicator of both OS (12.7 vs. 22.6 months, p = 0.003) and PFS (3.6 vs. 8.4 months, p p = 0.4818). On multivariable analysis, DXM use predicted an unfavorable OS hazard ratio (HR) = 1.72, p = 0.045). CONCLUSIONS: Our results with TMZ, BEV, and RT are similar to previous studies in terms of PFS and OS. DXM use during RT with concurrent TMZ correlated with reduced OS and PFS unless BEV was administered

First Bronze Age Human Mitogenomes from Calabria (Grotta Della Monaca, Southern Italy)

The Italian peninsula was host to a strong history of migration processes that shaped its genomic variability since prehistoric times. During the Metal Age, Sicily and Southern Italy were the protagonists of intense trade networks and settlements along the Mediterranean. Nonetheless, ancient DNA studies in Southern Italy are, at present, still limited to prehistoric and Roman Apulia. Here, we present the first mitogenomes from a Middle Bronze Age cave burial in Calabria to address this knowledge gap. We adopted a hybridization capture approach, which enabled the recovery of one complete and one partial mitochondrial genome. Phylogenetic analysis assigned these two individuals to the H1e and H5 subhaplogroups, respectively. This preliminary phylogenetic analysis supports affinities with coeval Sicilian populations, along with Linearbandkeramik and Bell Beaker cultures maternal lineages from Central Europe and Iberia. Our work represents a starting point which contributes to the comprehension of migrations and population dynamics in Southern Italy, and highlights this knowledge gap yet to be filled by genomic studies

Selective Inhibition of p300 HAT Blocks Cell Cycle Progression, Induces Cellular Senescence, and Inhibits the DNA Damage Response in Melanoma Cells

Epigenetic events, including covalent post-translational modifications of histones, have been demonstrated to have critical roles in tumor development and progression. The transcriptional coactivator p300/CBP possesses both histone acetyltransferase (HAT) activity and scaffolding properties that directly influence the transcriptional activation of targeted genes. We have used a potent and specific inhibitor of p300/CBP HAT activity, C646, in order to evaluate the functional contributions of p300/CBP HAT to tumor development and progression. Here we report that C646 inhibits the growth of human melanoma and other tumor cells and promotes cellular senescence. Global assessment of the p300 HAT transcriptome in human melanoma identified functional roles in promoting cell cycle progression, chromatin assembly, and activation of DNA repair pathways through direct transcriptional regulatory mechanisms. In addition, C646 is shown to promote sensitivity to DNA damaging agents, leading to the enhanced apoptosis of melanoma cells after combination treatment with cisplatin. Together, our data suggest that p300 HAT activity mediates critical growth regulatory pathways in tumor cells and may serve as a potential therapeutic target for melanoma and other malignancies by promoting cellular responses to DNA damaging agents that are currently ineffective against specific cancers

P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries

The critical role for ADP in arterial thrombogenesis was established by the clinical success of P2Y12 antagonists, currently used at doses that block 40–50% of the P2Y12 on platelets. This study was designed to determine the role of P2Y12 in platelet thrombosis and how its complete absence affects the thrombotic process. P2Y12-null mice were generated by a gene-targeting strategy. Using an in vivo mesenteric artery injury model and real-time continuous analysis of the thrombotic process, we observed that the time for appearance of first thrombus was delayed and that only small, unstable thrombi formed in P2Y12–/– mice without reaching occlusive size, in the absence of aspirin. Platelet adhesion to vWF was impaired in P2Y12–/– platelets. While adhesion to fibrinogen and collagen appeared normal, the platelets in thrombi from P2Y12–/– mice on collagen were less dense and less activated than their WT counterparts. P2Y12–/– platelet activation was also reduced in response to ADP or a PAR-4–activating peptide. Thus, P2Y12 is involved in several key steps of thrombosis: platelet adhesion/activation, thrombus growth, and stability. The data suggest that more aggressive strategies of P2Y12 antagonism will be antithrombotic without the requirement of aspirin cotherapy and may provide benefits even to the aspirin-nonresponder population