IL PROCESSO DI COMMERCIALIZZAZIONE DELL'ATTIVITA' DI RICERCA IN UNA MEDIA IMPRESA FARMACEUTICA ITALIANA. IL CASO ABIOGEN PHARMA S.P.A.

La ricerca nel campo delle life sciences ha compiuto importanti progressi, e il termine “biotecnologia” è ormai entrato a far parte del linguaggio comune. Nonostante vi siano ancora posizioni etiche contrastanti, sollevate dall’elevata sensibilità del tema e dal grande numero di stakeholders che gravitano intorno al mondo dell’healthcare, è ampiamente riconosciuto che, dopo le scienze dell’informazione, le biotecnologie costituiscono l’avanguardia dell’innovazione dei prossimi decenni, creando così nuove possibilità d’impresa per le realtà in grado di dimostrare un’eccellenza. Il settore biotech sta rivestendo un ruolo strategico all’interno delle politiche economiche di tutti i paesi industrializzati e, se i benefici delle nuove terapie iniziano ad essere evidenti sia da un’ottica sociale che da un punto di vista finanziario, sussiste una cultura ancora limitata delle problematiche che la “ricerca e sviluppo”, vero driver dell’innovazione, si trova ad affrontare. Il principale motivo che mi ha spinto alla trattazione di questo argomento, è data dalla sfida di fornire una descrizione del comparto biotech dall’ottica inedita della ricerca, un’attività che alcuni considerano “astratta”, mentre costituisce un settore a sé stante di immenso valore economico (in particolare nel pharma), con dinamiche competitive del tutto peculiari, ma ascrivibile, con le doverose cautele, ai modelli di studio tradizionali. Il filo conduttore di tutto l’elaborato è dato dall’utilizzo ragionato delle banche dati tipicamente impiegate dall’industria farmaceutica per la pianificazione strategica marketing-oriented. La prima parte va interpretata come una focalizzazione progressiva dal settore farmaceutico alla R&S biotecnologica, partendo da un’analisi quantitativa che evidenzia il peso crescente che stanno esercitando le biotecnologie in termini di quota di mercato, in particolare nell’area oncologico. Il capitolo prosegue con una definizione del prodotto e del target di riferimento del mercato della R&S, sottolineando le diverse esigenze che portano ad una partnership di tipo industriale o di tipo finanziario. In conclusione viene fornita una descrizione funzionale di Abiogen Pharma S.p.A., l’azienda farmaceutica oggetto del caso di studio. Nel secondo capitolo si approfondisce il modello tipico di sviluppo di un nuovo farmaco, con le relative problematiche; la descrizione del procedimento è propedeutica alla questione del rischio di insuccesso che, grazie agli studi sul cosiddetto “attrition rate”, è stato possibile quantificare. L’ultima sezione del capitolo descrive le ricerche di mercato orientate alla pianificazione strategica e alla determinazione del valore del progetto, ponendo l’accento sul supporto fondamentale dato delle banche dati disponibili. Infine verrà approfondita la metodologia tipica della valutazione dei progetti di ricerca, delineando in chiave critica quella standard (discounted cash flow method), e proponendone una nuova, più adatta alla mitigazione dei rischi affrontati (risk-adjusted discounted cash flow method) e applicata mediante l’ausilio dei diversi database. Il terzo capitolo tratta del caso reale che mi sono trovato ad affrontare durante l’esperienza di stage in Abiogen Pharma S.p.A.; l’azienda pisana ha mostrato da sempre una forte propensione all’innovazione e negli ultimi anni si è posta l’obiettivo di costituire una start-up capace di concorrere nel settore biotech. Dopo aver analizzato i motivi che hanno condotto a scegliere il modello societario della “virtual company”, ho provveduto a fornire una valutazione economica delle sei tecnologie in pipeline utilizzando la nuova metodologia suggerita. Nel finale ho proposto un possibile marketing mix del settore R&S, applicando il noto modello delle “4 P”

Fine-tuning on Clean Data for End-to-End Speech Translation: FBK @ IWSLT 2018

This paper describes FBK's submission to the end-to-end English-German speech translation task at IWSLT 2018. Our system relies on a state-of-the-art model based on LSTMs and CNNs, where the CNNs are used to reduce the temporal dimension of the audio input, which is in general much higher than machine translation input. Our model was trained only on the audio-to-text parallel data released for the task, and fine-tuned on cleaned subsets of the original training corpus. The addition of weight normalization and label smoothing improved the baseline system by 1.0 BLEU point on our validation set. The final submission also featured checkpoint averaging within a training run and ensemble decoding of models trained during multiple runs. On test data, our best single model obtained a BLEU score of 9.7, while the ensemble obtained a BLEU score of 10.24.Comment: 6 pages, 2 figures, system description at the 15th International Workshop on Spoken Language Translation (IWSLT) 201

Enhancing Transformer for End-to-end Speech-to-Text Translation

Neural end-to-end architectures have beenrecently proposed for spoken languagetranslation (SLT), following the state-of-the-art results obtained in machine translation (MT) and speech recognition (ASR).Motivated by this contiguity, we proposean SLT adaptation of Transformer (thestate-of-the-art architecture in MT), whichexploits the integration of ASR solutionsto cope with long input sequences featuring low information density. Long audiorepresentations hinder the training of largemodels due to Transformer’s quadraticmemory complexity.Moreover, for thesake of translation quality, handling suchsequences requires capturing both short-and long-range dependencies between bi-dimensional features. Focusing on Trans-former’s encoder, our adaptation is basedon:i)downsampling the input with con-volutional neural networks, which enablesmodel training on non cutting-edge GPUs,ii)modeling the bidimensional nature ofthe audio spectrogram with 2D components, andiii)adding a distance penaltyto the attention, which is able to bias ittowards short-range dependencies.Ourexperiments show that our SLT-adaptedTransformer outperforms the RNN-basedbaseline both in translation quality andtraining time, setting the state-of-the-artperformance on six language directions

Fine-tuning on Clean Data for End-to-End Speech Translation: FBK @ IWSLT 2018

This paper describes FBK’s submission to the end-to-end English-German speech translation task at IWSLT 2018. Our system relies on a state-of-the-art model based on LSTMs and CNNs, where the CNNs are used to reduce the temporal dimension of the audio input, which is in generalmuch higher than machine translation input. Our model wastrained only on the audio-to-text parallel data released forthe task, and fine-tuned on cleaned subsets of the originaltraining corpus. The addition of weight normalization andlabel smoothing improved the baseline system by1.0BLEUpoint on our validation set. The final submission also fea-tured checkpoint averaging within a training run and ensem-ble decoding of models trained during multiple runs. On testdata, our best single model obtained a BLEU score of9.7,while the ensemble obtained a BLEU score of10.24

Percutaneous image-guided cryoablation of osteoblastoma

International audienceOBJECTIVE. The aim of this observational study was to assess safety and clinical outcomes of percutaneous image-guided cryoablation (CA) to treat osteoblastomas (OBs) at various osseous sites. MATERIALS AND METHODS. A retrospective search was performed to identify patients presenting with painful OBs who underwent CA at the University Hospitals of Strasbourg between March 2007 and December 2018. Ten patients (seven men, three women; median age, 21 years old) were identified and included. Medical records were reviewed to assess complications and clinical outcomes. RESULTS. Median OB diameter was 16.5 mm (range, 16–28 mm). OBs were located in the spine (n = 7), calcaneus (n = 1), fibula (n = 1), and third metacarpal bone (n = 1). In 90% of cases (n = 9), one or more critical structures were within 1 cm of the OB (median distance, 5 mm; range, 2–8 mm), thus requiring extensive protective measures. Technical success was achieved in all cases. Two (20%) immediate neural complications were noted. One major complication was consistent with a permanent sensory deficit of the arm. One minor complication was consistent with a transient right Horner syndrome, which completely resolved after 48 hours with high-dose steroids. Median clinical follow-up was 12 months. Primary clinical success was 100% and 78% at 1 and 12 months of follow-up, respectively, with two patients presenting with recurring pain. CONCLUSION. Percutaneous image-guided CA represents an effective therapeutic option for patients affected by painful OBs; the safety profile of the procedure is acceptable as long as comprehensive protective measures are deployed in light of the frequent close proximity of critical structures

Correlation between fetal movement revealed in actography and fetal-neonatal well-being: observational study on 3,805 pregnancies followed in a Northern Italy tertiary care hospital.

PURPOSE OF INVESTIGATION: To evaluate the correlation between fetal movement revealed in cardiotocography and fetal-neonatal well-being as well as to assess the value of cardiotocography in our clinical practice. METHODS: Retrospective analysis of 3,805 pregnancies followed at Parma General Hospital. Exclusion criteria were cesarean section, preterm delivery, and stillbirth. We analyzed the predictive power of actography during the dilating and expulsive phases of labor by establishing a correlation between number of fetal movements and our neonatal indexes of well being, i.e., cardiotocographic score, Apgar index and neonatal pH value. Statistical tests used were Fisher's test, chi-square test (X2), Pearson correlation and Spearman Rho; p value was considered significant if it was less than 0.05. RESULTS: We considered 2,389 vaginal deliveries. Analyzing the correlation between fetal movement and cardiotocographic score in the two different phases of labor, the comparison among subpopulations identified by different cardiotocograph scores revealed no statistical difference. CONCLUSION: Cardiotocography is reconfirmed as a good instrument to evaluate neonatal outcome, while actigraphy cannot be used alone to define fetal well-being, mainly due to the inability to standardize assessment of the actographic study

Coexistence of adenomyosis and endometrioid endometrial cancer: Role in surgical guidance and prognosis estimation

The aim of the current study was to diagnose the concomitant presence of adenomyosis (AM) in endometrioid endometrial cancer (EEC) in order to evaluate its value as an oncological prognostic marker. A retrospective analysis of 289 patients diagnosed with EEC who underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic-lymphadenectomy was conducted. The total cohort included 37 patients in Group A (those with concomitant AM and EEC) and 252 patients in Group B (those affected only by EEC). The following factors were evaluated: Presence or absence of AM, tumor grade, depth of myometrial invasion, tumor size, lymphovascular space involvement, lymph node status, peritoneal cytology, concomitant detection of endometrial atypical-hyperplasia or polypoid endometrial features and tumor stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Uterine examination of different sections of uterine cervix, corpus, myomas and cervical or endometrial polyps was performed. The diagnosis of AM was confirmed when the distance between the lower border of the endometrium and the foci of the endometrial glands and stroma was >2.5 mm. Parametric and nonparametric statistical tests were performed when possible, continuous variables were analyzed using a Student's t-test, and categorical variables were analyzed by the \u3c72 test or Fisher's exact test. The association between FIGO stage and group was determined to be significant: 83.8% of Group A patients were categorized as FIGO stage I, vs. 68.7% of Group B patients. In addition, Group A was associated with lower grades in FIGO stage, myometrial invasion, lymphovascular space involvement, lymph node involvement and tumor size. The findings suggest that the intraoperative evaluation of the presence of AM in patients with EEC may aid surgeons in estimating oncological risk and in selecting the most appropriate surgical treatment