New Perspective in HCV Clinical and Economical Management of the Current and Future Therapies

Hepatitis C virus (HCV) is a progressive disease that infects more than 185 million individuals worldwide and is associated with persistence of viral replication and ongoing necroinflammation and fibrosis. To date 20% of patients chronically infected with HCV progress to cirrhosis. Epidemiological studies demonstrate that the incidence of HCV is not well known, because acute infection is generally asymptomatic. The global prevalence is about 2.2% and there is a large degree of geographic variability. Before the 2011, the gold standard of therapy for the treatment of chronic hepatitis C (CHC) was based on the combination of pegylated Interferon (peg-IFN) and Ribavirin (RBV). However, several aspects related to safety profile limited their use in clinical practice. In the recent years, thanks to basic research on HCV structure and replicative cycle, it has been possible to develop direct acting antiviral drugs that have dramatically increased the viral clearance rate. Specifically, the advent of the triple therapy employing direct acting antivirals has dramatically increased the viral clearance rate, from less than 10%, with the initial regimen of IFN monotherapy, to more than 95% with the current therapy. Even though new medications for hepatitis C are effective disease modifiers and have the potential, in a long term perspective, to eradicate the pathology, the cost of new treatments are unlikely to be sustainable for the NHSs. The evidence documenting the effectiveness and tolerability of the new therapies for HCV and several pharmacoeconomic analysis, shows that despite the cost, the new treatments can be considered cost-effective in the long period. However, the health care systems are unable to compensate the height financial resources immediately needed for treating patients with the long terms savings that will be obtained from the eradication of HCV. Indeed, new pharmaceutical policy and a global commitment is required to improve strategies of treatment and price negotiation with pharmaceutical companies to move from a theoretical cost-effectiveness approach to a practical cost-sustainable reality

Il lavoro a termine verso la liberalizzazione?

L’emanazione del decreto legge 20 marzo 2014, n. 34, convertito, con modificazioni, dalla legge 16 maggio 2014, n. 78 ci costringe a ritornare sull’argomento a breve distanza di tempo dal commento alle modifiche normative in materia di contratto a tempo determinato apportate nel 2013 dal governo Letta, che, a sua volta, seguivano a breve distanza quelle di cui alla riforma Fornero del 2012. Sia consentito, a tal proposito, osservare come il continuo rimaneggiamento di un istituto contrattuale è già di per sé un elemento negativo. A prescindere, cioè, dal merito dei recenti interventi succedutisi in materia dobbiamo ancora una volta evidenziare come siffatto modo di legiferare, per successive stratificazioni, e di regolare una fattispecie contrattuale così importante quale quella qui in esame con frequenti adattamenti che risentono dei diversi “umori” delle varie fasi storico-politiche nei quali sono adottati e rispondono ad obiettivi economico-sociali e di politica del diritto spesso tra loro contrastanti, non contribuisce di certo alla creazione di un sistema normativo chiaro, unitario e coerente, di cui da tempo, ormai, si sente il bisogno

In attesa della nuova riforma: una rilettura del lavoro a termine

Ad un primo esame, la norma della legge n. 92/2012 che si occupa del contratto a termine, frutto di diverse modifiche “in corsa”, seppure aiuta a sciogliere alcuni nodi della disciplina in materia, dovuti anche allo scombinato sovrapporsi degli interventi legislativi del 2001, del 2003, del 2007 e del 2010, appare ulteriormente foriera di difficoltà interpretative. Si renderà, quindi, ancora una volta necessario il consueto costruttivo impegno della dottrina giuslavoristica, storicamente fornito per la ricomposizione di un quadro normativo di complessa esegesi, avendo come obiettivo quello di coniugare diritti e tutele dei lavoratori ed esigenze delle imprese, legate alle profonde modificazioni in atto delle modalità della produzione e dell’organizzazione del lavoro. A prescindere da ogni giudizio sull'opportunità di un nuovo intervento legislativo, posto che, come ricordato, secondo molti osservatori la riforma del 2001 aveva già correttamente disciplinato la materia ai sensi della direttiva comunitaria, e tralasciando il fatto che il legislatore continua «nella tragica scelta di aggiungere norme a norme, contribuendo non poco alla creazione di una selva infernale spesso incomprensibile e destinata ad aumentare ancora il contenzioso» ( ) e ancora lasciando da parte il dibattito (i.e. le polemiche) in ordine alla (mancata) “concertazione” e persino “dialogo sociale” in proposito ( ), occorre, anzitutto, osservare come il legislatore, con operazione non facilmente spiegabile, abbia coniato una nuova formulazione del comma 01 dell’art. 1 del decreto legislativo del 2001, che oggi, appunto, in sostituzione della precedente («il contratto di lavoro subordinato è stipulato di regola a tempo indeterminato»), così recita: «il contratto di lavoro subordinato a tempo indeterminato costituisce la forma comune di rapporto di lavoro». Ci si deve, dunque, anzitutto, interrogare sul significato e sull’effettiva portata della predetta nuova formulazione

Assessment of Post-Earthquake Damage: St. Salvatore Church in Acquapagana, Central Italy

This article proposes a multidisciplinary approach for the assessment of seismic damage from the perspective of conservation and prevention. A comparison of the state of damage has been carried out in a case study, St. Salvatore church in Acquapagana (MC), as an example of church, which underwent two important seismic events in the Central Italy area, the 1997 and the 2016 earthquakes. The comparison of the state of damage passes through the following stages: (a) the territorial seismic overview; (b) the historical description and material analysis; (c) the identification of macro-elements with activated damage mechanisms; (d) the comparison between the two seismic events both from a territorial-and building-scale perspective. This work puts together the archived and the on-site survey data with those elaborated starting from seismogenic information, available from the National Seismological Institute, and it provides a strategy also for other similar conditions. This work is to be considered a contribution to a wider study that could be carried out in the areas hit by the 2016 earthquake. It could also represent a way to collect documentation in the post-earthquake phase, improving the effectiveness of procedures currently applied to the first level of damage assessment

“Pacchetto lavoro” e assenza di contenuti previdenziali

Con il recente “Pacchetto Lavoro” varato con d.l. 28 giugno 2013, n. 76, conv. con modif. dalla l. 9 agosto 2013, n. 99 il legislatore interviene ancora sul mercato del lavoro, secondo una prospettiva di affannosa ri-cerca di quella ideale configurazione dello stesso in grado di accompagnare, in modo più efficace, la ripresa economica e la crescita dell’occupazione. Detto della consueta difficoltà di lettura del testo legislativo nel suo complesso considerato, testo, peraltro, ancora una volta infarcito di continui rinvii ad altri testi normati-vi già per loro conto strutturalmente complessi, nel presente scritto si tenta un primo rapido esame di quel-le disposizioni che più direttamente interessano l’ambito previdenziale. Il reticolato normativo costituito dal d.l. n. 76 del 2013, come convertito dalla l. n. 99 del 2013, oltre ad avere come suo “entroterra” legislativo necessitato la difficile situazione economico-sociale che attraversa il nostro Paese, contempla anche, per l’individuazione della ratio a esso sottesa, il complessivo quadro di riferimento del mercato del lavoro, nella sua configurazione attuale come delineato dagli ultimi interventi legislativi sulla materia. Per queste ragioni, dunque, il contributo muove dalla complessa odierna fase congiunturale e dalle ragioni dell’intervento legi-slativo qui in esame, per poi giungere, dopo alcune brevi considerazioni generali sulle misure adottate dal Governo, nel loro complesso considerate, alla individuazione dei caratteri “previdenziali” delle misure stes-se (e, soprattutto, di quello che, sotto tale profilo, è ancora una volta assente)

Nature-derived compounds modulating Wnt/β-catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases

Abstract The Wnt/β-catenin signaling is a conserved pathway that has a crucial role in embryonic and adult life. Dysregulation of the Wnt/β-catenin pathway has been associated with diseases including cancer, and components of the signaling have been proposed as innovative therapeutic targets, mainly for cancer therapy. The attention of the worldwide researchers paid to this issue is increasing, also in view of the therapeutic potential of these agents in diseases, such as Parkinson's disease (PD), for which no cure is existing today. Much evidence indicates that abnormal Wnt/β-catenin signaling is involved in tumor immunology and the targeting of Wnt/β-catenin pathway has been also proposed as an attractive strategy to potentiate cancer immunotherapy. During the last decade, several products, including naturally occurring dietary agents as well as a wide variety of products from plant sources, including curcunim, quercetin, berberin, and ginsenosides, have been identified as potent modulators of the Wnt/β-catenin signaling and have gained interest as promising candidates for the development of chemopreventive or therapeutic drugs for cancer. In this review we make an overview of the nature-derived compounds reported to have antitumor activity by modulating the Wnt/β-catenin signaling, also focusing on extraction methods, chemical features, and bio-activity assays used for the screening of these compounds

Diagnostic performance of Wells score combined with point-of-care lung and venous ultrasound in suspected pulmonary embolism

Objective: Lung and venous ultrasound are bedside diagnostic tools increasingly used in the early diagnostic approach of suspected pulmonary embolism (PE). However, the possibility of improving the conventional prediction rule for PE by integrating ultrasound has never been investigated. Methods: We performed lung and venous ultrasound in consecutive patients suspected of PE in four emergency departments. Conventional Wells score (Ws) was adjudicated by the attending physician, and ultrasound was performed by one of 20 investigators. Signs of deep venous thrombosis (DVT) at venous ultrasound and signs of pulmonary infarcts or alternative diagnoses at lung ultrasound were considered to recalculate two items of the Ws: signs and symptoms of DVT and alternative diagnosis less likely than PE. The diagnostic performances of the ultrasound-enhanced Ws (USWs) and Ws were then compared after confirmation of the final diagnosis. Results: A total of 446 patients were studied. PE was confirmed in 125 patients (28%). USWs performed significantly better than Ws, with a sensitivity of 69.6% versus 57.6% and a specificity of 88.2% versus 68.2%. In combination with D-dimer, USWs showed an optimal failure rate (0.8%) and a significantly superior efficiency than Ws (32.3% vs. 27.2%). A strategy based on lung and venous ultrasound combined with D-dimer would allow to avoid CT pulmonary angiography in 50.5% of patients with suspected PE, compared to 27.2% when the rule without ultrasound is applied. Conclusions: A pretest risk stratification enhanced by ultrasound of lung and venous performs better than Ws in the early diagnostic process of PE

A symmetric polymer blend confined into a film with antisymmetric surfaces: interplay between wetting behavior and phase diagram

We study the phase behavior of a symmetric binary polymer blend which is confined into a thin film. The film surfaces interact with the monomers via short range potentials. We calculate the phase behavior within the self-consistent field theory of Gaussian chains. Over a wide range of parameters we find strong first order wetting transitions for the semi-infinite system, and the interplay between the wetting/prewetting behavior and the phase diagram in confined geometry is investigated. Antisymmetric boundaries, where one surface attracts the A component with the same strength than the opposite surface attracts the B component, are applied. The phase transition does not occur close to the bulk critical temperature but in the vicinity of the wetting transition. For very thin films or weak surface fields one finds a single critical point at $\phi_c=1/2$. For thicker films or stronger surface fields the phase diagram exhibits two critical points and two concomitant coexistence regions. Only below a triple point there is a single two phase coexistence region. When we increase the film thickness the two coexistence regions become the prewetting lines of the semi-infinite system, while the triple temperature converges towards the wetting transition temperature from above. The behavior close to the tricritical point, which separates phase diagrams with one and two critical points, is studied in the framework of a Ginzburg-Landau ansatz. Two-dimensional profiles of the interface between the laterally coexisting phases are calculated, and the interfacial and line tensions analyzed. The effect of fluctuations and corrections to the self-consistent field theory are discussed.Comment: Phys.Rev.E in prin