De novo unbalanced translocations have a complex history/aetiology

We investigated 52 cases of de novo unbalanced translocations, consisting in a terminally deleted or inverted-duplicated deleted (inv-dup del) 46th chromosome to which the distal portion of another chromosome or its opposite end was transposed. Array CGH, whole-genome sequencing, qPCR, FISH, and trio genotyping were applied. A biparental origin of the deletion and duplication was detected in 6 cases, whereas in 46, both imbalances have the same parental origin. Moreover, the duplicated region was of maternal origin in more than half of the cases, with 25% of them showing two maternal and one paternal haplotype. In all these cases, maternal age was increased. These findings indicate that the primary driver for the occurrence of the de novo unbalanced translocations is a maternal meiotic non-disjunction, followed by partial trisomy rescue of the supernumerary chromosome present in the trisomic zygote. In contrast, asymmetric breakage of a dicentric chromosome, originated either at the meiosis or postzygotically, in which the two resulting chromosomes, one being deleted and the other one inv-dup del, are repaired by telomere capture, appears at the basis of all inv-dup del translocations. Notably, this mechanism also fits with the origin of some simple translocations in which the duplicated region was of paternal origin. In all cases, the signature at the translocation junctions was that of non-homologous end joining (NHEJ) rather than non-allelic homologous recombination (NAHR). Our data imply that there is no risk of recurrence in the following pregnancies for any of the de novo unbalanced translocations we discuss here

Analisi dei tempi d\u2019attesa tra le varie fasi di gestione dei carcinomi mammari screening-detected a Trieste nel biennio 2013-2014: come si pu\uf2 migliorare?

Gli indicatori relativi ai tempi di attesa sono difficili da rispettare, come recentemente evidenziato al XIII Convegno ONS 2015 . Per questo motivo \ue8 fondamentale identificare in quale momento della gestione dei carcinomi screening-detected si concentrino i ritardi e stabilirne le cause (se attribuibili alla paziente o all\u2019organizzazione del programma o intrinseci al tipo di lesione) cos\uec da proporre mirate modifiche migliorative. Metodi: L\u2019analisi riguarda 146 carcinomi screening-detected consecutivi (biennio 2013-2014). Sono stati misurati i tempi tra le varie fasi diagnostiche (Mammografia di I\ub0 livello, Richiamo II\ub0 livello, I\ub0 approfondimento cito/microistologico, Comunicazione diagnosi) e i tempi chirurgici (Visita chirurgica, Intervento chirurgico, Referto istologico con marcatori biologici, Visita oncologica). Per ogni fase sono stati calcolati i tempi medi/mediani rappresentati tramite box plot e giustificati gli outliers.Risultati: La latenza nella presa in carico chirurgica \ue8 legato alla complessit\ue0 degli esami preoperatori (3) (tempo mediano tra richiamo al II\ub0 livello ed intervento: 53 giorni (se unico esame pre-operatorio) vs 73 (se pi\uf9 di un esame pre-operatorio, p<0.0001), mentre rispetto ad un recente studio (4) il tempo mediano tra visita chirurgica e intervento non \ue8 aumentato per i casi con necessit\ue0 di RM (28 vs 26 giorni, p=0.13), perch\ue9 gi\ue0 programmata in fase preoperatoria. Per i casi con mastectomia sempre con ricostruzione, si registra un tempo medio dalla visita chirurgica all\u2019intervento di 7 giorni superiore rispetto alle quadrantectomie. Ulteriore criticit\ue0 \ue8 il tempo mediano tra intervento e visita oncologica (44 giorni), attribuibile in parte ad un \u201critardo\u201d nella disponibilit\ue0 dei marcatori biomolecolari (soprattutto HER2/FISH) ed in parte a rinvii dell\u2019appuntamento da parte della paziente stessa Conclusioni: Soltanto un attento monitoraggio del turnaround time dell\u2019intero percorso delle pazienti con carcinoma screening detected consente l\u2019identificazione dei punti di debolezza su cui intervenire efficacemente per garantire il rispetto degli indicatori

Passano gli anni e il nuovo non viene

pp. da 102 a 122

I consumi di suolo. Metodi ed esperienze di analisi

pp. 228-25

Foreign exchange trading: A risk-averse batch reinforcement learning approach

Automated Trading Systems' impact on financial markets is ever growing, particularly on the intraday Foreign Exchange market. Historically, the FX trading systems are based on advanced statistical methods and technical analysis able to extract trading signals from financial data. In this work, we explore how to find a trading strategy via Reinforcement Learning by means of a state-of-the-art batch algorithm, Fitted Q-Iteration. Furthermore, we include a Multi-Objective formulation of the problem to keep the risk of noisy profits under control. We show that the algorithm is able to detect favorable temporal patterns, which are used by the agent to maximize the return. Finally, we show that as risk aversion increases, the resulting policies become smoother, as the portfolio positions are held for longer periods

RAPID AND ACCURATE QUANTIFICATION OF DIFFERENT HCV GENOTYPES BY LIGHTCYCLER REAT TIME PCR AND DIRECT SEQUENCING OG HCV AMPLICONS

RAPID AND ACCURATE QUANTIFICATION OF DIFFERENT HCV GENOTYPES BY LIGHTCYCLER REAT TIME PCR AND DIRECT SEQUENCING OG HCV AMPLICON

"AF HeartTeam" guided indication for stand-alone thoracoscopic left atrial ablation and left atrial appendage closure

Background:Traditional surgical treatment for patients with atrial fibrillation (AF) is performed via sternotomy and on cardiopulmonary bypass. It is very effective in regard to rhythm control, but remains unpopular due to its invasiveness. Truly endoscopic AF treatments have decreased the threshold for electrophysiologists (and cardiologists) to refer, and the reluctance of patients to accept a standalone surgical approach. Practice guidelines from around the world have recognized this as an acceptable therapeutic approach. Current guidelines recommend the HeartTeam approach in treating these complex AF cases. In this study we report our experience with AF HeartTeam approach for surgical stand-alone AF ablation. Methods: The AF HeartTeam Program began in 2013, patients qualified for inclusion if either of the following was present: failed catheter ablation and/or medication, not suitable for catheter ablation, contraindication to anticoagulation, or patients preferring such an approach. All patients with a complex AF history were assessed by the AF HeartTeam, from which 42 patients were deemed suitable for a totally endoscopic AF procedure (epicardial ablation and LAA closure). Endpoints were intraoperative bidirectional block of the pulmonary veins and closure of left atrial appendage confirmed by transesophageal echocardiography (TEE). Post discharge rhythm follow-up was performed after 3 and 12, 24 and 36 months. Anticoagulation was discontinued 6 weeks after the procedure in patients after documented LAA closure. Results: In total 42 patients underwent the endoscopic procedure (Median CHA2DS2-VASC=3 (1-6), HAS-BLED=2 (1-6)) for paroxysmal (15/42) and non-paroxysmal AF (27/42) respectively. Bidirectional block was obtained in all patients and complete LAA closure was obtained in all but one Patient on TEE (41/42). In one patient the LAA was not addressed due to extensive adhesions. Two patients underwent median sternotomy because of bleeding during the endoscopic surgery early in the series. There were no deaths. Procedure duration was a median of 124min (Range 83-211) and duration of hospitalization was median of 5 days (Range 3-12). During 36 months follow-up survival free of mortality, thromboembolic events or strokes was 100%. Twelve month freedom from atrial arrhythmia off anti-arrhythmic medication was 93% and 89% for paroxysmal and non-paroxysmal patients respectively. 6/42 patients who had an AF recurrence during the follow-up underwent touch-up catheter ablation. Conclusions: Atrial fibrillation heart team approach provides excellent outcomes for patients with AF. This approach is beneficial for patients after failed catheter ablation or not candidates for such and offers a very effective mid-term outcome data. In addition to effective rhythm control the protective effect of epicardial LAA closure may play an important role in effectively reducing stroke. The creation of an AF HeartTeam as recommended by the guidelines insures unbiased therapies and provides access to this minimally invasive but effective therapeutic option for AF patients