Obesity and Breast Cancer: Interaction or Interference with the Response to Therapy?

Background: Aromatase inhibitors (AI) are widely used for treating hormone-sensitive breast cancer (BC). Obesity, however, due to aromatase-mediated androgen conversion into estradiol in the peripheral adipose tissue, might impair AI inhibitory capacity. We aimed at identifying a cut-off of body mass index (BMI) with significant prognostic impact, in a cohort of stage I-II BC patients on systemic adjuvant therapy with AI. Methods: we retrospectively evaluated routinely collected baseline parameters. The optimal BMI cut-off affecting disease-free survival (DFS) in AI-treated BC patients was identified through maximally selected rank statistics; non-linear association between BMI and DFS in the AI cohort was assessed by hazard-ratio-smoothed curve analysis using BMI as continuous variable. The impact of the BMI cut-off on survival outcomes was estimated through Kaplan-Meier plots, with log-rank test and hazard ratio estimation comparing patient subgroups. Results: A total of 319 BC patients under adjuvant endocrine therapy and/or adjuvant chemotherapy were included. Curve-fitting analysis showed that for a BMI cut-off >29 in AI-treated BC patients (n = 172), DFS was increasingly deteriorating and that the impact of BMI on 2-year DFS identified a cut-off specific only for the cohort of postmenopausal BC patients under adjuvant therapy with AI. Conclusion: in radically resected hormone-sensitive BC patients undergoing neoadjuvant or adjuvant chemotherapy and treated with AI, obesity represents a risk factor for recurrence, with a significantly reduced 2-year DFS

PCSK6 and Survival in Idiopathic Pulmonary Fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed. Objectives: To identify and validate molecular determinants of IPF survival. Methods: A staged genome-wide association study was performed using paired genomic and survival data. Stage I cases were drawn from centers across the United States and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplantation-free survival (TFS). Stage I variants with nominal significance (P < 5 x 10(-5)) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance (P < 5 x 10(-8)). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance. Measurements and Main Results: After quality controls, 1,481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of PCSK6 (proprotein convertase subtilisin/kexin type 6) reaching genome-wide significance (hazard ratio, 4.11 [95% confidence interval, 2.54-6.67]; P = 9.45 x 10(-9)). PCSK6 protein was highly expressed in IPF lung parenchyma. PCSK6 lung staining intensity, peripheral blood gene expression, and plasma concentration were associated with reduced TFS. Conclusions: We identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein plays a potentially important role in IPF progression

Comparison Wage in Trade Union Decision Making

The starting point of this paper is the idea that trade unions and individual workers pay attention to wage settlements in similar sectors of the economy. The foundations of this concept can be found in other social sciences and also in the literature of psychological economics. However, it has not received much attention in connection to union decision making. This comparison or reference wage enters the decision making of the union (i.e. the union utility function). In this paper, we employ a union utility function which incorporates this concept. The analysis is conducted in a bargaining framework and the results show the effects on the optimal wage of important variables like comparison wage, unemployment benefit, union power and of the weight that the union places on the comparison wag

Italiani e antifascisti in Tunisia. Percorsi di una difficile identità

Nel periodo delle speranze suscitate dalla vittoria Fronte popolare in Francia e dalla guerra di Spagna, la Tunisia, per nulla chiusa in un isolamento provinciale, era una sorta di laboratorio politico di presenze antifasciste (sindacalisti, anarchici, comunisti, socialisti, repubblicani) molto vicino alla realtà europea. La numerosa comunità italiana (quasi 100.000 individui) era costituita in parte da borghesia coloniale, in parte da rifugiati politici e soprattutto da masse di emigrati provenienti dal Mezzogiorno in cerca di lavoro. La fascistizzazione promossa dalle autorità consolari si rivelò un processo lungo e difficile e non riuscì mai a stravolgere del tutto l’identità culturale, laica e pluralista della comunità, la cui tradizione libertaria non venne mai del tutto meno. In questo ambiente una parte della giovane generazione della borghesia italiana manifestò il suo antifascismo, prima nella forma di una contestazione goliardica, come ricerca di modelli di vita anticonformistici, poi dando vita ad un’opposizione sempre più radicale e consapevole, le cui tappe principali furono l’adesine al partito comunista, il rifiuto del colonialismo e dell’equazione fascismo=italianità e la proposta di un’immagine e di un’idea di nazionalità e di patria radicalmente diverse da quelle diffuse dal regime. Nel 1937 l’assassinio di Giuseppe Miceli, un giovane falegname siciliano, in una spedizione punitiva, che produsse una grande reazione popolare antifascista, pose definitivamente termine al “dilettantismo” del gruppo. Il Centro Estero del partito comunista italiano inviò a Tunisi Giorgio Amendola e Velio Spano, per dare respiro internazionale all’attività dei tunisini. Ma la rigidità ideologica dei partiti aderenti al Comintern, insieme allo scoppio della guerra, finì col comportare la fine dell’alleanza con gli altri antifascisti. In seguito molti di questo gruppo (i fratelli Bensasson, i fratelli Gallico, Marco Vais, Maurizio Valenzi ecc.) raggiunsero l’Italia dopo la guerra e ricoprirono incarichi significativi nel PCI. Il libro ricostruisce le vicende di questi giovani antifascisti attraverso la memorialistica, le carte d’archivio delle spie del consolato fascista e il periodico «L’Italiano di Tunisi» da loro fondato

Immediate and selective maternal brain responses to own infant faces

Infant faces elicit caregiving in adults. In previous research on brain responses to images of infant faces, the faces were unknown to participants. This study investigated EEG in primiparous mothers of 3- to 6-month-old infants viewing their own infant's face compared to an unfamiliar but appearance-matched infant's face. Spectral power was calculated and compared, and power at three EEG bands (delta, theta, and gamma) was found to differ between faces. Brain responses among primiparous mothers distinguish images of their own versus unfamiliar infants.Accepted versio