Biotecnología del cultivo in vitro de algas rojas (Rhodophyta) de interes industrial

Premio extraordinario, Área de Experimentales.

Interessi finanziari e diritto sanzionatorio comunitario

L’oggetto della presente tesi di ricerca è l’analisi della situazione attuale della protezione degli interessi finanziari delle Comunità Europee, oltre che le sue prospettive di futuro. Il lavoro è suddiviso in due grandi parti. La prima studia il regime giuridico del Diritto sanzionatorio comunitario, cioè, la competenza sanzionatoria dell’Unione Europea. Questa sezione è stata ricostruita prendendo in considerazione i precetti normativi del Diritto originario e derivato, oltre che le principali sentenze della Corte di Giustizia, tra cui assumono particolare rilievo le sentenze di 27 ottobre 1992, Germania c. Commissione, affare C-240/90 e di 13 settembre 2005 e di 23 ottobre 2007, Commissione c. Consiglio, affari C-176/03 e C-440/05. A questo segue l’analisi del ruolo dei diritti fondamentali nell’ordinamento comunitario, così come la rilevanza della Convenzione Europea dei Diritti dell’Uomo e la Corte Europea dei Diritti dell’Uomo. Il secondo capitolo si sofferma particolarmente sullo studio delle sanzioni comunitarie, classificandole in ragione della loro natura giuridica alla luce anche dei principi generali di legalità, di proporzionalità, di colpevolezza e del non bis in idem. La seconda sezione sviluppa un’analisi dettagliata del regime giuridico della protezione degli interessi finanziari comunitari. Questa parte viene costruita indagando tutta l’evoluzione normativa e istituzionale, in considerazione anche delle novità più recenti (ad esempio, l’istituzione del Pubblico Ministero Europeo). In questo contesto si definisce il contenuto del concetto di interessi finanziari comunitari, dato che non esiste un’analoga definizione comunitaria della fattispecie. L’attenzione del dottorando si concentra poi sulla Convenzione avente ad oggetto la tutela degli interessi finanziari delle Comunità Europee e i regolamenti del Consiglio n. 2988/95 e 2185/96, che costituiscono la parte generale del Diritto sanzionatorio comunitario. Alla fine si esamina la ricezione della Convenzione PIF nel Codice Penale spagnolo e i principali problemi di cui derivano. L’originalità dell’approccio proposto deriva dell’assenza di un lavoro recente che, in modo esclusivo e concreto, analizzi la protezione amministrativa e penale degli interessi finanziari della Comunità. Inoltre, la Carta Europea di Diritti Fondamentali e il Trattato di Lisbona sono due grandi novità che diventeranno una realtà tra poco tempo.

Circoli collaterali porto-sistemici all'eco-color-Doppler addominale in pazienti con ipertensione portale cirrotica: correlazione con il gradiente porto-epatico e valore prognostico

Background. Abdominal porto-systemic collaterals (APSC) on Color-Doppler ultrasound are a frequent finding in portal hypertensive cirrhotic patients. In patients with cirrhosis, an HVPG ≥ 16mmHg has been shown to be associated with increased mortality in two studies. Non-invasive indicators of HVPG ≥ 16 mmHg might define a subgroup of high-risk patients, but data on this aspect are lacking. Aims. We aimed to investigate whether HVPG predicts mortality in patients with clinically significant portal hypertension, and if APSC may predict a severe portal hypertensive state (i.e. HVPG≥16mmHg) in patients with cirrhosis and untreated portal hypertension. Methods. We analysed paired HVPG and ultrasonographic data of 86 untreated portal hypertensive cirrhotic patients. On abdominal echo-color-Doppler data on presence, type and number of APSC were prospectively collected. HVPG was measured following published guidelines. Clinical, laboratory and endoscopic data were available in all cases. First decompensation of cirrhosis and liver-disease related mortality on follow-up (mean 28±20 months) were recorded. Results. 73% of patients had compensated cirrhosis, while 27% were decompensated. All patients had an HVPG≥10 mmHg (mean 17.8±5.1 mmHg). 58% of compensated patients and 82% of decompensated patients had an HVPG over 16 mmHg. 25% had no varices, 28% had small varices, and 47% had medium/large varices. HVPG was higher in patients with esophageal varices vs. patients without varices (19.0±4.8 vs. 14.1±4.2mmHg, p<0.0001), and correlated with Child-Pugh score (R=0.494,p=0.019). 36 (42%) patients had APSC were more frequent in decompensated patients (60% vs. 35%, p=0.03) and in patients with esophageal varices (52% vs. 9%,p=0.001). HVPG was higher in patients with APSC compared with those without PSC (19.9± 4.6 vs. 16.2± 4.9mmHg, p=0.001). The prevalence of APSC was higher in patients with HVPG≥16mmHg vs. those with HVPG<16mmHg (57% vs. 13%,p<0.0001). Decompensation was significantly more frequent in patients with HVPG≥16mmHg vs. HVPG<16mmHg (35.1% vs. 11.5%, p=0.02). On multivariate analysis only HVPG and bilirubin were independent predictors of first decompensation. 10 patients died during follow-up. All had an HVPG≥16 mmHg (26% vs. 0% in patients with HVPG <16mmHg,p=0.04). On multivariate analysis only MELD score and HVPG ≥16mmHg were independent predictors of mortality. In compensated patients the detection of APSC predicted an HVPG≥16mmHg with 92% specificity, 54% sensitivity, positive and negative likelihood ratio 7.03 and 0.50, which implies that the demonstration of APSC on ultrasound increased the probability of HVPG≥16mmHg from 58% to 91%. Conclusions. HVPG maintains an independent prognostic value in the subset of patients with cirrhosis and clinically significant portal hypertension. The presence of APSC is a specific indicator of severe portal hypertension in patients with cirrhosis. Detection of APSC on ultrasound allows the non-invasive identification of a subgroup of compensated patients with bad prognosis, avoiding the invasive measurement of HVPG.

Bronchial artery embolization in patients with hemoptysis including follow-up

BACKGROUND; Hemoptysis can be an acute medical emergency, which can be localized angiographically and controlled by therapeutic intervention.

Assessment of patient setup errors in IGRT in combination with a six degrees of freedom couch

PURPOSE The range of patient setup errors in six dimensions detected in clinical routine for cranial as well as for extracranial treatments, were analyzed while performing linear accelerator based stereotactic treatments with frameless patient setup systems. Additionally, the need for re-verification of the patient setup for situations where couch rotations are involved was analyzed for patients treated in the cranial region. METHODS AND MATERIALS A total of 2185 initial (i.e. after pre-positioning the patient with the infrared system but before image guidance) patient setup errors (1705 in the cranial and 480 in the extracranial region) obtained by using ExacTrac (BrainLAB AG, Feldkirchen, Germany) were analyzed. Additionally, the patient setup errors as a function of the couch rotation angle were obtained by analyzing 242 setup errors in the cranial region. Before the couch was rotated, the patient setup error was corrected at couch rotation angle 0° with the aid of image guidance and the six degrees of freedom (6DoF) couch. For both situations attainment rates for two different tolerances (tolerance A: ± 0.5mm, ± 0.5°; tolerance B: ± 1.0 mm, ± 1.0°) were calculated. RESULTS The mean (± one standard deviation) initial patient setup errors for the cranial cases were -0.24 ± 1.21°, -0.23 ± 0.91° and -0.03 ± 1.07° for the pitch, roll and couch rotation axes and 0.10 ± 1.17 mm, 0.10 ± 1.62 mm and 0.11 ± 1.29 mm for the lateral, longitudinal and vertical axes, respectively. Attainment rate (all six axes simultaneously) for tolerance A was 0.6% and 13.1% for tolerance B, respectively. For the extracranial cases the corresponding values were -0.21 ± 0.95°, -0.05 ± 1.08° and -0.14 ± 1.02° for the pitch, roll and couch rotation axes and 0.15 ± 1.77 mm, 0.62 ± 1.94 mm and -0.40 ± 2.15 mm for the lateral, longitudinal and vertical axes. Attainment rate (all six axes simultaneously) for tolerance A was 0.0% and 3.1% for tolerance B, respectively. After initial setup correction and rotation of the couch to treatment position a re-correction has to be performed in 77.4% of all cases to fulfill tolerance A and in 15.6% of all cases to fulfill tolerance B. CONCLUSION The analysis of the data shows that all six axes of a 6DoF couch are used extensively for patient setup in clinical routine. In order to fulfill high patient setup accuracies (e.g. for stereotactic treatments), a 6DoF couch is recommended. Moreover, re-verification of the patient setup after rotating the couch is required in clinical routine.

Effectiveness of the Call in Beach Volleyball Attacking Play

In beach volleyball the setter has the opportunity to give her or his hitter a “call”. The call intends that the setter suggests to her or his partner where to place the attack in the opponent’s court. The effectiveness of a call is still unknown. We investigated the women’s and men’s Swiss National Beach Volleyball Championships in 2011 and analyzed 2185 attacks. We found large differences between female and male players. While men called in only 38.4% of attacks, women used calls in 85.5% of attacks. If the male players followed a given call, 63% of the attacks were successful. The success rate of attacks without any call was 55.8% and 47.6% when the call was ignored. These differences were not significant (χ2(2) = 4.55, p = 0.103). In women’s beach volleyball, the rate of successful attacks was 61.5% when a call was followed, 35% for attacks without a call, and 42.6% when a call was ignored. The differences were highly significant (χ2(2) = 23.42, p < 0.0005). Taking into account the findings of the present study, we suggested that the call was effective in women’s beach volleyball, while its effect in men’s game was unclear. Considering the quality of calls we indicate that there is a significant potential to increase the effectiveness of a call.

Reconstructing 4000 years of mass movement and tsunami history in a deep peri-Alpine lake (Lake Geneva, France-Switzerland)

The study of mass movements in lake sediments provides insights into past natural hazards at historic and prehistoric timescales. Sediments from the deep basin of Lake Geneva reveal a succession of six large-scale (volumes of 22 × 106 to 250 × 106 m3) mass-transport deposits, associated with five mass-movement events within 2600 years (4000 cal bp to 563 ad). The mass-transport deposits result from: (i) lateral slope failures (mass-transport deposit B at 3895 ± 225 cal bp and mass-transport deposits A and C at 3683 ± 128 cal bp); and (ii) Rhône delta collapses (mass-transport deposits D to G dated at 2650 ± 150 cal bp, 2185 ± 85 cal bp, 1920 ± 120 cal bp and 563 ad, respectively). Mass-transport deposits A and C were most probably triggered by an earthquake, whereas the Rhône delta collapses were likely to be due to sediment overload with a rockfall as the external trigger (mass-transport deposit G, the Tauredunum event in 563 ad known from historical records), an earthquake (mass-transport deposit E) or unknown external triggers (mass-transport deposits D and F). Independent of their origin and trigger mechanisms, numerical simulations show that all of these recorded mass-transport deposits are large enough to have generated at least metre-scale tsunamis during mass movement initiation. Since the Tauredunum event in 563 ad, two small-scale (volumes of 1 to 2 × 106 m3) mass-transport deposits (H and I) are present in the seismic record, both of which are associated with small lateral slope failures. Mass-transport deposits H and I might be related to earthquakes in Lausanne/Geneva (possibly) 1322 ad and Aigle 1584 ad, respectively. The sedimentary record of the deep basin of Lake Geneva, in combination with the historical record, show that during the past 3695 years, at least six tsunamis were generated by mass movements, indicating that the tsunami hazard in the Lake Geneva region should not be neglected, although such events are not frequent with a recurrence time of 0·0016 yr−1.

Antibody-Drug Conjugates for Tumor Targeting-Novel Conjugation Chemistries and the Promise of non-IgG Binding Proteins

Antibody-drug conjugates (ADCs) have emerged as a promising class of anticancer agents, combining the specificity of antibodies for tumor targeting and the destructive potential of highly potent drugs as payload. An essential component of these immunoconjugates is a bifunctional linker capable of reacting with the antibody and the payload to assemble a functional entity. Linker design is fundamental, as it must provide high stability in the circulation to prevent premature drug release, but be capable of releasing the active drug inside the target cell upon receptor-mediated endocytosis. Although ADCs have demonstrated an increased therapeutic window, compared to conventional chemotherapy in recent clinical trials, therapeutic success rates are still far from optimal. To explore other regimes of half-life variation and drug conjugation stoichiometries, it is necessary to investigate additional binding proteins which offer access to a wide range of formats, all with molecularly defined drug conjugation. Here, we delineate recent progress with site-specific and biorthogonal conjugation chemistries, and discuss alternative, biophysically more stable protein scaffolds like Designed Ankyrin Repeat Proteins (DARPins), which may provide such additional engineering opportunities for drug conjugates with improved pharmacological performance.