The Identification of Risk Factors: the Control of the Significance Level in Multiple Comparisons

A common problem in statistical medical analyses is the identification of risk factors associated with a certain disease. The collected sampled data are used to assess simultaneously more hypotheses, each of which assesses the influence of one factor. It is well known that the simultaneous assessment of two or more hypotheses entails a rise in the probability of rejecting at least one of the true null partial hypotheses. In this paper the rise in this probability is approximately evaluated for different levels of dependance between factors by means of a permutation-based procedure. The paper also proposes a procedure which computes an adjusted p-value for each test of the partial hypotheses in such a way that the global hypothesis that none of the factors have influence is assessed at a prefixed significance level. A simulation study is performed to check the power of the proposed procedure

Assonanze e dissonanze nel passaggio alla valutazione on-line della didattica

Le norme relative alla raccolta delle informazioni sui giudizi espressi dagli studenti sono state recentemente modificate secondo le linee guida previste dall’ANVUR.. Tra le molte novità introdotte, risultano particolarmente rilevanti le modifiche apportate in merito a: i) obbligatorietà della valutazione da parte degli studenti; ii) estensione della rilevazione ai non frequentanti; iii) avvio della modalità di rilevazione on-line. Come si può facilmente comprendere, si tratta di aspetti certamente rilevanti che possono comportare significative modifiche non solo in termini delimitazione dell’universo osservato, ma anche nel modo stesso di esprimere il proprio giudizio . Obiettivo di questo lavoro è pertanto quello di analizzare i possibili effetti di tali cambiamenti, limitatamente al giudizio espresso dai frequentanti, confrontando l’andamento delle valutazioni del 2012/13, condotte con la tradizionale rilevazione cartacea in classe, con quelle del 2013/14 realizzate invece con procedura on-line

Fusion of HCV nonstructural antigen to MHC class II-associated invariant chain enhances T-cell responses induced by vectored vaccines in nonhuman primates

Despite viral vectors being potent inducers of antigen-specific T cells, strategies to further improve their immunogenicity are actively pursued. Of the numerous approaches investigated, fusion of the encoded antigen to major histocompatibility complex class II–associated invariant chain (Ii) has been reported to enhance CD8(+) T-cell responses. We have previously shown that adenovirus vaccine encoding nonstructural (NS) hepatitis C virus (HCV) proteins induces potent T-cell responses in humans. However, even higher T-cell responses might be required to achieve efficacy against different HCV genotypes or therapeutic effect in chronically infected HCV patients. In this study, we assessed fusion of the HCV NS antigen to murine and human Ii expressed by the chimpanzee adenovirus vector ChAd3 or recombinant modified vaccinia Ankara in mice and nonhuman primates (NHPs). A dramatic increase was observed in outbred mice in which vaccination with ChAd3 expressing the fusion antigen resulted in a 10-fold increase in interferon-γ(+) CD8(+) T cells. In NHPs, CD8(+) T-cell responses were enhanced and accelerated with vectors encoding the Ii-fused antigen. These data show for the first time that the enhancement induced by vector vaccines encoding li-fused antigen was not species specific and can be translated from mice to NHPs, opening the way for testing in humans

Combined adenovirus vector and hepatitis C virus envelope protein prime-boost regimen elicits T cell and neutralizing antibody immune responses

Despite the recent progress in the development of new antiviral agents, hepatitis C virus (HCV) infection remains a major global health problem, and there is a need for a preventive vaccine. We previously reported that adenoviral vectors expressing HCV nonstructural proteins elicit protective T cell responses in chimpanzees and were immunogenic in healthy volunteers. Furthermore, recombinant HCV E1E2 protein formulated with adjuvant MF59 induced protective antibody responses in chimpanzees and was immunogenic in humans. To develop an HCV vaccine capable of inducing both T cell and antibody responses, we constructed adenoviral vectors expressing full-length and truncated E1E2 envelope glycoproteins from HCV genotype 1b. Heterologous prime-boost immunization regimens with adenovirus and recombinant E1E2 glycoprotein (genotype 1a) plus MF59 were evaluated in mice and guinea pigs. Adenovirus prime and protein boost induced broad HCV-specific CD8+ and CD4+ T cell responses and functional Th1-type IgG responses. Immune sera neutralized luciferase reporter pseudoparticles expressing HCV envelope glycoproteins (HCVpp) and a diverse panel of recombinant cell culture-derived HCV (HCVcc) strains and limited cell-to-cell HCV transmission. This study demonstrated that combining adenovirus vector with protein antigen can induce strong antibody and T cell responses that surpass immune responses achieved by either vaccine alone