Cova dels Jurats at Calescoves (Alaior, Minorca). A Cave Shrine in the Talayotic context?

Excavations carried out in the Cova dels Jurats between 2010 and 2012 served to establish that, unlike the rest of the caves Calescoves, this one functioned as a sanctuary, with two different phases. The first one corresponds to the Final Talayotic Period, as the first cave shrine documented in the Talayotic culture. In Roman times, the place was still used as a sanctuary, but with a totally different ritual, linked to the inscriptions discovered at the entrance of the cave.

Entretenimientos, fiestas, juegos y placeres en la corte de los reyes de Aragón en el siglo xiv Steffano

Este trabajo estudia la presencia e importancia de las diversiones y el placer en distintos momentos de la vida de la corte de los reyes de Aragón: las prostitutas, dirigidas por el rey Arlot, la música, el juego, el baile o los juglares, observando el aumento de su presencia a lo largo del siglo xiv, con el correlativo aumento de los gastos. También se observa el incremento en el lujo y la complejidad de estas actividades y la siempre mayor presencia de elementos espectaculares como bestias, carros, figuras alegóricas y otros entremeses en coronaciones, bodas o entradas reales, todos ellos aspectos de la progresiva glorificación de la monarquía.

Quintus Curtius before his sources: the episode of Alexander and the Scythians on the Tanais

Quintus Curtius found in his sources a speech where a Scythian censured Alexander, followed by the King’s reply. Curtius drastically abridged this second discourse in order to highlight the criticism of the Macedonian. The Scythian’s words have a striking rhetorical language and some allusions taken from Greek literature, in addition to possible indirect references to Caligula. Curtius declares that he follows his source word-for-word aiming to justify these inconsistencies, but also trying to hide the manipulations he has done to achieve his own narrative purposes.

Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial.

Background: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. Patients and methods: We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). Conclusion: This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.

FcγRIIa and FcγRIIIa polymorphisms and cetuximab benefit in the microscopic disease

Purpose: FcγR polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX ± cetuximab in high-risk, locally advanced rectal cancer.

Experimental Design: FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms.

Results: Genotyping was successfully performed in 105 of 164 (64%) patients (CAPOX = 54, CAPOX-C = 51). No deviation from the Hardy–Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. FcγRIIa-131R (HR, 0.38; P = 0.058) and FcγRIIIa-158F alleles (HR, 0.21; P = 0.007) predicted improved progression-free survival (PFS) in patients treated with cetuximab. In the CAPOX-C arm, carriers of both 131R and 158F alleles had a statistically significant improvement in PFS (5 years: 78.4%; HR, 0.22; P = 0.002) and overall survival (OS; 5 years: 86.4%; HR, 0.24; P = 0.018) when compared with patients homozygous for 131H and/or 158V (5-year PFS: 35.7%; 5-year OS: 57.1%). An interaction between cetuximab benefit and 131R and 158F alleles was found for PFS (P = 0.017) and remained significant after adjusting for prognostic variables (P = 0.003).

Conclusion: This is the first study investigating FcγRIIa and FcγRIIIa polymorphisms in patients with early-stage colorectal cancer treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles.

TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial.

In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging-defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found (P <.05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS.

RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial.

Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial.

Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of cetuximab on study end-points in the RAS wild-type population was analysed.

Results: Eleven (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149 (52%) assessable patients were RAS wild-type (CAPOX, n = 40; CAPOX-C, n = 38). In this population, after a median follow-up of 63.8 months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p = 0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p = 0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p = 0.20).

Conclusions: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted.

HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab.

BACKGROUND: HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT±cetuximab in the EXPERT-C trial. PATIENTS AND METHODS: Eligible patients with available tumour tissue for HER2 analysis were included. HER2 expression was determined by immunohistochemistry (IHC) in pre-treatment biopsies and/or surgical specimens (score 0-3+). Immunostaining was scored according to the consensus panel recommendations on HER2 scoring for gastric cancer. Tumours with equivocal IHC result (2+) were tested for HER2 amplification by D-ISH. Tumours with IHC 3+ or D-ISH ratio ≥2.0 were classified as HER2+. The impact of HER2 on primary and secondary end points of the study was analysed. RESULTS: Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3 of 104 (2.9%) and 3 of 114 (2.6%) were HER2+, respectively. In 77 patients with paired specimens, concordance for HER2 status was found in 74 (96%). Overall, 141 patients were assessable for HER2 and 6 out of 141 (4.3%) had HER2 overexpression and/or amplification. The median follow-up was 58.6 months. HER2 was not associated with a difference in the outcome for any of the study end points, including in the subset of 90 KRAS/BRAF wild-type patients treated±cetuximab. CONCLUSIONS: Based on the low prevalence of expression as recorded in the EXPERT-C trial, HER2 does not appear to represent a useful therapeutic target in high-risk rectal cancer. However, the role of HER2 as a potential predictive biomarker of resistance to anti-EGFR-based treatments and a therapeutic target in anti-EGFR refractory metastatic colorectal cancer (CRC) warrants further investigation. TRIAL REGISTRATION: ISRCTN Register: 99828560.

Determinazione di mercurio mediante DMA-80

I fenomeni di contaminazione antropica da mercurio sono sempre più diffusi e preoccupanti, tanto da spingere all’ attivazione di politiche nazionali ed internazionali atte a ridurre o almeno “contenere” i rischi legati a questo metallo tossico. Con quest’obiettivo è prioritaria la necessità di determinare la concentrazione del metallo in maniera veloce, economica ed efficiente. Il seguente report intende fornire informazioni utili nell’utilizzo dello spettrofotometro DMA-80 nell’analisi di Hg in varie matrici ambientali. Lo strumento è stato acquistato dall’IAMC-CNR di Capo Granitola per rispondere alle esigenze progettuali del progetto “Dinamica dei processi di evasione e deposizione del mercurio nell’area industrializzata della Rada di Augusta e definizioni delle mappe di rischio sanitario per le popolazioni residenti” (prot.n°0000466 18/2/2011) finanziato dall’Assessorato alla Salute della Regione Sicilia con l’obbiettivo di verificare il potenziale impatto del mercurio, derivato dalle emissioni dei reflui non trattati dell’impianto di cloro-soda SYNDIAL Priolo-Gargallo sulle popolazioni residenti nell’aria fortemente industrializzata di Augusta-Melilli (Siracusa).

Report tecnico – BioQuestionario e BioScoperta Applicazioni mobili per imparare giocando

L’informazione in campo ambientale assume un’importanza fondamentale in relazione all’obiettivo di accrescere il livello di consapevolezza e di sensibilità in relazione al concetto di ambiente, sia al fine di promuovere comportamenti coerenti con il principio di sviluppo sostenibile, sia per contribuire allo sviluppo di una responsabilità individuale e collettiva. Le tecnologie mobili nascono e si evolvono a partire dalla necessità dell’uomo di espandere i propri limiti e dall’esigenza di avere la possibilità di comunicare e accedere alle informazioni in maniera diretta e immediata. L'utilizzo di dispositivi mobili, quali smartphone e tablet, è in netta crescita in tutte le categorie di utenza e nei differenti contesti sociali. Possedere un dispositivo mobile dotato di accesso alla rete internet permette di avere il sapere a portata di mano e di comunicare con utenti in tutto il modo senza barriere fisiche e temporali. Inoltre, possono essere strumenti di grande aiuto, sia nel campo lavorativo che nel tempo libero, grazie all’utilizzo di innumerevoli applicazioni create ad hoc per l'acquisizione di informazioni e la loro fruizione. L’aspirazione del progetto, inserito nel Sistema di Comunicazione, Informazione e Diffusione dell’Osservatorio della Biodiversità della Sicilia, è la realizzazione di una applicazione che permetta ai visitatori di approfondire e consolidare i luoghi e forme della conoscenza offerti, durante la visita dell’Osservatorio della Biodiversità Regione Sicilia, dal personale qualificato rivestito dalle figure di ricercatori e tecnologi dell’IAMC CNR della sede di Capo Granitola. Gli scopi principali sono la comunicazione, l’informazione e l’educazione per lo sviluppo di conoscenze e sensibilità sul tema della Biodiversità per spronare gli utenti alla salvaguardia del territorio, rendendo facilmente accessibile l’approfondimento dei concetti riguardanti numerose specie e habitat del nostro territorio, attraverso una dimensione scientifica di stampo ludico.