Le Finanziarie regionali come operatori di private equity

Obiettivo del presente lavoro è approntare un’analisi interpretativa dell’operatività dalle Finanziarie regionali, valutarne gli investimenti in capitale di rischio e, in particolare, l’attività di private equity, evidenziando le tendenze in atto, i possibili percorsi evolutivi e le eventuali criticità. La metodologia adottata ha previsto un’articolazione del lavoro lungo due principali direttive: un’analisi di tipo quantitativo sui bilanci di sette esercizi (dal 2002 al 2008), con la finalità di indagare nel dettaglio gli aspetti economici, finanziari e patrimoniali delle Finanziarie regionali attive sul territorio italiano; un’analisi qualitativa basata su un’approfondita rassegna della letteratura internazionale e su interviste mirate ad un campione ampiamente rappresentativo della popolazione osservata. I risultati raggiunti fanno ragionevolmente supporre che sia in atto una profonda ristrutturazione dell’intero sistema delle Finanziarie, che ha visto innanzitutto aumentare il controllo pubblico nella compagine sociale. L’indagine contabile ha permesso di identificare la presenza di due modelli di business ben differenziati: alcune Finanziarie sono orientate ad attività con forte contenuto di intermediazione finanziaria; altre invece sono focalizzate sull’attività di erogazione di servizi sia finanziari di consulenza che reali. L’investimento in capitale di rischio costituisce un attività centrale per le Finanziarie regionali; l’analisi dedicata a tali impieghi ha permesso di individuare, tra esse, alcune realtà tipiche del merchant banking, e più di frequente, del modello di holding. Complessivamente le Finanziarie campionate detengono oltre 400 partecipazioni per un valore che supera 1,7 miliardi di euro; prevalentemente concentrati su una ristretta cerchia di realtà spesso con impatto strategico sul territorio, ovvero strumentali. Segnatamente all’attività di private equity, è stato possibile rilevare come la politica d’investimento delle Finanziarie regionali sia complementare rispetto a quella mediamente espressa dal mercato domestico, anche se restano critici, anche per le Finanziarie, gli investimenti su imprese target con fatturato compreso tra 2 e 10 milioni di euro. Le evidenze circa la struttura dei contratti segnalano una parziale conformità alla best practice individuata dalla letteratura internazionale. In particolare l’uso limitato dello stage financing, la bassa partecipazione alla gestione sono le principali criticità individuate. Infine, della fase di riorganizzazione che pare interessare il sistema delle Finanziarie, si trova conferma nella percezione dei suoi operatori. Interpellati sul futuro dell’attività di investimento in capitale di rischio, hanno fornito indicazioni che consentono di concludere l’esistenza di una polarizzazione delle Finanziarie su due gruppi: da un lato quelle che implementeranno, più o meno, l’attività di private equity, dall’altro quelle che, viceversa, abbandoneranno tale strumento. La normativa sulle società a partecipazione pubblica regionale e la scarsa autonomia nella gestione delle misure affidate sono ritenute, dalle Finanziarie “interessate”, il principale fattore di freno alla loro crescita nel mercato del private equity.

In vitro generation and characterization of acute myeloid leukemia-reactive CD8 + cytotoxic T-lymphocyte clones from healthy donors

Donor-derived CD8+ cytotoxic T lymphocytes (CTLs) eliminating host leukemic cells mediate curative graft-versus-leukemia (GVL) reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The leukemia-reactive CTLs recognize hematopoiesis-restricted or broadly expressed minor histocompatibility and leukemia-associated peptide antigens that are presented by human leukocyte antigen (HLA) class I molecules on recipient cells. The development of allogeneic CTL therapy in acute myeloid leukemia (AML) is hampered by the poor efficiency of current techniques for generating leukemia-reactive CTLs from unprimed healthy donors in vitro. In this work, a novel allogeneic mini-mixed lymphocyte/leukemia culture (mini-MLLC) approach was established by stimulating CD8+ T cells isolated from peripheral blood of healthy donors at comparably low numbers (i.e. 10e4/well) with HLA class I-matched primary AML blasts in 96-well microtiter plates. Before culture, CD8+ T cells were immunomagnetically separated into CD62L(high)+ and CD62L(low)+/neg subsets enriched for naive/central memory and effector memory cells, respectively. The application of 96-well microtiter plates aimed at creating multiple different responder-stimulator cell compositions in order to provide for the growth of leukemia-reactive CTLs optimized culture conditions by chance. The culture medium was supplemented with interleukin (IL)-7, IL-12, and IL-15. On day 14, IL-12 was replaced by IL-2. In eight different related and unrelated donor/AML pairs with complete HLA class I match, numerous CTL populations were isolated that specifically lysed myeloid leukemias in association with various HLA-A, -B, or -C alleles. These CTLs recognized neither lymphoblastoid B cell lines of donor and patient origin nor primary B cell leukemias expressing the corresponding HLA restriction element. CTLs expressed T cell receptors of single V-beta chain families, indicating their clonality. The vast majority of CTL clones were obtained from mini-MLLCs initiated with CD8+ CD62L(high)+ cells. Using antigen-specific stimulation, multiple CTL populations were amplified to 10e8-10e10 cells within six to eight weeks. The capability of mini-MLLC derived AML-reactive CTL clones to inhibit the engraftment of human primary AML blasts was investigated in the immunodeficient nonobese diabetic/severe combined immune deficient IL-2 receptor common γ-chain deficient (NOD/SCID IL2Rγnull) mouse model. The leukemic engraftment in NOD/SCID IL2Rγnull was specifically prevented if inoculated AML blasts had been pre-incubated in vitro with AML-reactive CTLs, but not with anti-melanoma control CTLs. These results demonstrate that myeloid leukemia-specific CTL clones capable of preventing AML engraftment in mice can be rapidly isolated from CD8+ CD62L(high)+ T cells of healthy donors in vitro. The efficient generation and expansion of these CTLs by the newly established mini-MLLC approach opens the door for several potential applications. First, CTLs can be used within T cell-driven antigen identification strategies to extend the panel of molecularly defined AML antigens that are recognizable by T cells of healthy donors. Second, because these CTLs can be isolated from the stem cell donor by mini-MLLC prior to transplantation, they could be infused into AML patients as a part of the stem cell allograft, or early after transplantation when the leukemia burden is low. The capability of these T cells to expand and function in vivo might require the simultaneous administration of AML-reactive CD4+ T cells generated by a similar in vitro strategy or, less complex, the co-transfer of CD8-depleted donor lymphocytes. To prepare clinical testing, the mini-MLLC approach should now be translated into a protocol that is compatible with good manufacturing practice guidelines.

Migrazione verso una architettura rest di un applicativo per l'inter library loan

Questo lavoro di tesi �si basa sull'estendere l'architettura del software NILDE - Network Inter Library Document Exchange attraverso un processo di migrazione verso servizi REST (REpresentational State Transfer) utilizzando e ampliando metodologie, best practice e frameworks che hanno permesso lo sviluppo di API Pubbliche e Private utilizzabili da utenti esterni.

Laboratory based investigations for diagnosing gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) still remains the most common out- GI-related condition in the out-patient setting. While primary care physicians often use empiric trials with proton pump inhibitors (PPI trial) to diagnose GERD, often specialised tests are required to confirm or exclude gastroesophageal reflux causing esophageal or extraesophageal symptoms. The most commonly used procedures to diagnose GERD include: conventional (catheter based) pH monitoring, wireless esophageal pH monitoring (Bravo), bilirubin monitoring (Bilitec), and combined multichannel intraluminal impedance-pH monitoring (MII-pH). Each technique has strengths and limitations of which clinicians and investigators should be aware when deciding which one to choose.

Adverse effects of drugs on the esophagus

Given the function of the esophagus to transport orally ingested solids and liquids into the stomach there are several medications with adverse effect on esophageal structures and function. Various pharmacologic agents can induce esophageal injury, promote gastroesophageal reflux by decreasing lower esophageal sphincter tone or affect esophageal perception and motility. The risks of bisphosphonates, doxycycline, ferrous sulfate, ascorbic acid, aspirin/NSAIDs and chemotherapeutic agents to induce esophageal lesions have been documented in case reports and short series. In addition to direct mucosal injury, many commonly used medications including nitroglycerins, anticholinergics, beta-adrenergic agonists, aminophyllines, and benzodiazepines promote/facilitate gastroesophageal reflux by reducing lower esophageal sphincter pressure. Additional evidence accumulates on the adverse effects of various medications on esophageal motility and perception. The treatment of medication-induced esophageal lesions includes (1) identifying and discontinuing the causative medication, (2) promoting healing of esophageal injury by decreasing esophageal acid exposure or coating already existing esophageal lesions, (3) eventual use of protective compounds.

Alcoholic steatohepatitis

Severe alcoholic steatohepatitis has a poor prognosis and is characterized by jaundice and signs of liver failure. Its incidence is unknown, but prevalence is around 20% in cohorts of alcoholics undergoing liver biopsy. Diagnosis is established with elevated liver transaminases, neutrophil counts, serum bilirubin, and impaired coagulation and a history of excessive alcohol consumption, and exclusion of other etiologies. Histology is helpful but not mandatory. Prognostic scores include the Maddrey's discriminant function, the model of end-stage liver disease, and the Glasgow Alcoholic Hepatitis Score. Pathophysiology involves hepatic fat storage, increased hepatic uptake of gut-derived endotoxins triggering Kupffer cell activation and release of proinflammatory triggers, induction of cytochrome P4502E1 producing toxic acetaldehyde and reactive oxygen species, and ethanol-mediated hyperhomocysteinemia causing endoplasmic reticulum stress. Treatment includes abstinence, enteral nutrition, corticosteroids, and possibly pentoxifylline. A debate is ongoing whether certain patients with severe alcoholic steatohepatitis could be eligible for liver transplantation.

Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial

Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care.

Genetics of GHRH, GHRH-receptor, GH and GH-receptor: its impact on pharmacogenetics

When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required and, appropriate consideration should be given to genetic defects causing GH deficiency (GHD). Because Insulin-like-Growth Factor-I (IGF-I) plays a pivotal role, GHD could also be considered as a form of IGF-I deficiency (IGFD). Although IGFD can develop at any level of the GHRH-GH-IGF axis, a differentiation should be made between GHD (absent to low GH in circulation) and IGFD (normal to high GH in circulation). The main focus of this review is on the GH-gene, the various gene alterations and their possible impact on the pituitary gland. However, although transcription factors regulating the pituitary gland development may cause multiple pituitary hormone deficiency they may present initially as GHD. These defects are discussed in various different chapters within this book, whereas, the impact of alterations of the GHRH-, GHRH-receptor- --as well as the GH-receptor (GHR) gene--will be discussed here.