Academic literature on the topic 'Associazione statistica'

L'analisi è stata effettuata individuando le argomentazioni comuni o comunque assai similari esistenti fra i differenti commenti operati dai Nefrologi intervenuti nella discussione sulle scarsità della DP, considerati gli items di base. Ad essi è stato dato un punteggio arbitrario fra 0 e 2 per ogni singolo autore a seconda della rilevanza espressa dall'autore, la cui somma ha dato il peso totale dell'item, espresso in percento sulla somma totale degli items. Ciò ha dato luogo a due classificazioni delle cause individuate, la prima secondo i 13 items individuati, la seconda per associazione logica fra gli items. In ambedue le classificazioni il minor punteggio è dovuto ad un'ipotizzata non necessità della DP in Italia, mentre le classificazioni si diversificano per il punteggio più elevato, legato a responsabilità dei nefrologi stessi per varie cause nella prima classificazione e nella seconda a palese responsabilità dello Stato. Punteggi significativi sono legati ad un'insufficiente formazione ed informazione dei nefrologi, e nella prima classificazione all'intervento del privato nella terapia dialitica.

Il presente studio retrospettivo a singolo cieco si pone come obbiettivo quello di valutare in che percentuale di casi di pazienti che si presentano con sintomatologia compatibile con neurite vestibolare acuta, con e senza perdita oggettiva della funzione vestibulare (VFL), sia presente un conflitto neurovascolare fra il nervo vestibolococleare e la arteria cerebellare anteroinferiore (AICA). 58 pazienti con sintomatologia suggestiva per neurite vestibolare acuta, valutati con RMN presso un centro di terzo livello, sono stati confrontati con 61 pazienti asintomatici. I radiologi hanno dato valutato la presenza di conflitto neurovascolare, in assenza di dati clinici, conferendo ai rilievi oggettivi una valutazione in una scala da 0 a 3 a seconda che il contatto fosse: nesuno; inferiore a 2 mm; superiore ai 2 mm; presenza di vacular loop. I reperti neurootologici sono stati quindi raccolti all’oscuro del risultato dell’imaging. La funzione vestibolare è stata testata con prova calorica bitermica. Alla prova calorica 26 casi (45%) hanno mostrato segni oggettivi di deficit vestibolare (Gruppo A), 32 casi (55%) non hanno invece mostrato alcun deficit labirintico (Gruppo B). Il gruppo A ha incluso 13 casi (50%) con evidenza di conflitto neurovascolare (NVC), il gruppo B ha incluso 26 casi con NVC (82%) (p = 0.012) mentre i controlli hanno incluso 16 casi con NVC (26%). La differenza fra i tre gruppi ha mostrato significatività statistica (p<0.001). Il Gruppo B ha mostrati un associazione con un grading di conflitto piu elevato rispetto al Gruppo A (p = 0.009). La presenza di NVC non ha avuto un associazione statisticamente significativa ne con la presenza di SNHL ne con la presenza di acufene (p > 0.05). I nostri dati indicano che la presenza di conflitti neurovascolari a livello dell’angolo pontocerebellare è superiore in quei pazienti che in presenza di una sintomatologia compatibile con neurite vestibolare acuta abbiano una funzionalità simmetrica alla prova calorica.

Le malattie rare raggruppano un numero elevato di patologie molto diverse tra loro, accumunate, dalla bassissima frequenza statistica nella popolazione (penetranza). Ne consegue una scarsissima numerosità di pazienti per ogni singola patologia e una loro distribuzione in diverse aree geografiche, fattori che comportano oggettive difficoltà nel reclutamento dei pazienti in studi sperimentali e nel coordinamento e organizzazione della ricerca con conseguente ridotta possibilità di effettuare studi clinici e ricerche di carattere genetico. In tale quadro, al fine di fare fronte alle drammatiche necessità di assistenza socio-sanitaria, cura e riabilitazione dei malati rari, sono sorte, in gran parte per merito degli stessi familiari, le associazioni di malati rari. Attualmente tali associazioni svolgono un’attività significativa nella proposizione, organizzazione, partecipazione diretta e pubblicazione dei risultati di ricerche scientifiche. Tale ruolo, rende le associazioni dei pazienti protagoniste anche nel sostegno all’organizzazione e realizzazione di studi clinici e sperimentazioni di farmaci in modo del tutto autonomo e indipendente da controlli da parte delle autorità sanitarie e dei comitati etici. Tale fenomeno noto come “Research Led by Participants” è stato reso possibile dalle enormi potenzialità di contatto e organizzazione offerte dalla rete che ha consentito la creazione di comunità virtuali di pazienti, di siti e blog dedicati all’informazione e comunicazione, e più recentemente, alla raccolta di dati, alla pubblicazione di risultati di ricerche condotte dai malati, nonché al reclutamento degli stessi per la conduzione di tali studi, secondo il modello proposto, ad esempio, dal sito PatientsLikeMe. Non possono tuttavia essere trascurati gli importanti aspetti etici implicati dalla ricerca condotta dai partecipanti. Tali aspetti concernono, come evidente, sia la validità scientifica di tali studi che la protezione dei soggeti che aderiscono alla sperimentazione. Si tratta di una forma di sperimentazione del tutto nuova che richiede la capacità di proporre una modalità di gestione condivisa tra cittadini/pazienti, “terzo settore”, ricercatori, istituzioni e comitati etici in grado di valorizzarne i potenziali benefici conoscitivi creando regole etiche “misurate” su tali circostanze. Nell’articolo sarà proposto un modello teorico di governance del fenomeno e saranno indicati possibili criteri etici operativi. ---------- Rare diseases gather up a large number of different pathologies, all very different among them but similar for the low statistical attendance of population (penetrance). Therefore there is a very low number of patients sick of the same pathology and their presence in different geographical areas makes objectively difficult to recruit patients in order to study their disease and coordinate and organize the research of the pathology. As a consequence there is a very reduced possibility to carry on clinical studies and genetic researches. In this framework, in order to face the dramatic necessity of sociological and sanitary assistance, treatment and rehabilitation of the rare patients, families members generally organize Rare Diseases Patient Organizations. At the moment these organizations develop an important activity with regard to organization, proposals, direct participation and publication of the scientific research results. These organizations also play an important part in supporting the organization and the realization of clinical trials. They play in total autonomy and are independent from every ethical and scientific oversight by the sanitary authorities and ethical committees. This extraordinary event known as “Research Led by Participants”, has been realized thanks to the large contacts possibilities and organization offered by the web which made possible the creation of virtual communities of patients, of blog and web site for information and communication and, more recently, for collecting statistical data, publication of the patients research results and the recruitment of patients in order to manage the studies following the rules and models proposed, for example, by the web site “PatientsLikeMe”. We must however put in evidence the important ethical issues involved in the research led by the participants. These aspects concern, obviously, either the scientific validity of these studies or the protection of the subjects who accept to be submitted to the experimentation. It is a completely new way of experimentation that requires the capacity to propose and follow a governance that must be accepted and shared by citizens/patients, “third sector”, research workers, institutions and ethical committees able to exploit the potential advantageous knowledge and create ethical rules inspired to those new situations. In this article it will be proposed a theoretical model of governance of this phenomenon and also it will be outlined ethical rules for operative plans.

Anesthesiologists consider professional insurance and its medico-legal problems as a remarkable aspect of their job. “Associazione Anestesisti Rianimatori Ospedalieri Italiani—Emergenza ed Area Critica” (AAROI-EMAC) is the Italian professional association of anesthesiologists and intensivists that works to train its subscribers on safety measures. This is a retrospective observational study on an insurance complaints database for anesthetic accidents that result in injuries to patients. The analyzed period runs from 1 January 2014 to 31 December 2016. A total of 1309 complaints related to 873 insurance claims were analyzed. Criminal complaints comprised 805 (64.4%) of the total, and civil complaints were 445 (35.6%). The iatrogenic damage claimed included: death (58% of the cases); peripheral nerve damage (8%); spinal cord injuries (5%); unspecified injuries (7%); dental damage (4%); infections (3%); needing second surgical procedure (2%); and other injuries (13%). There is a statistical significance between the size of the hospital and the number of the claims: small hospital complaints comprised 40.1% of the cases, while complaints against medium-sized and large hospitals constituted 20.6% of the cases (χ2GL = 8 = 39.87, p = 0.00). In Italy, anesthesiologists and intensivists are often involved in litigation even when they are not directly responsible for iatrogenic injuries, and the most frequent claims in ICU are related post-operative complications.

Objetivou-se estimar os parâmetros genéticos e fenotípicos de características reprodutivas de fêmeas bovinas da raça Chianina criadas em diferentes rebanhos participantes da Associazione Nazionale Allevatori Bovini Italiani da Carne (ANABIC). As características estudadas foram idade ao primeiro parto (IPP), primeiro intervalo de partos (IDP1) e intervalo médio de partos (IMDP). As análises estatísticas foram realizadas pelo procedimento General Linear Model (GLM) do programa estatístico SAS (Statistical Analysis System) e os componentes de variância foram estimados pelo método de máxima verossimilhança restrita utilizando-se o software MTDFREML sob modelo animal. Os números de observações utilizados para IPP, IDP1 e IMDP foram, respectivamente, 31.023; 23.998 e 94.497 e as médias encontradas, em dias, 1.037,69 ± 186,37; 457,93 ± 96,80 e 436,26 ± 90,83 para IPP, IDP1, IDPM. Todas as características avaliadas foram influenciadas pelo rebanho. Verificou-se efeito de estação e ano de nascimento da vaca sobre a IPP. O IDP1 e o IDPM foram influenciados por rebanho, estação e ano do parto precedente, observando-se efeito também da ordem de parição sobre o IDPM. As estimativas de herdabilidade para IPP, IDP1 e IDPM foram, respectivamente de 0,36 ± 0,014; 0,13 ± 0,014 e 0,05 ± 0,004. A repetibilidade para IDPM foi de 0,075 ± 0,004. A utilização de IPP e IDP1 em programas de melhoramento genético pode resultar em maior precocidade e mais alto potencial para longevidade nestes rebanhos.

AbstractItalian physicians who, from Oct. 1979 to April 1981 directed an emergency medical team in the Ogaden refugee camps of the Qorioley district of Somalia, report on location, general set-up, vital statistics, health aspects, water and food supply, sanitation, disposal of waste matter, health hazards, spread and control of diseases, health education, and planning of health services and health teams.Invited by the Caritas of Somalia and the United Nations High Commissioner for Refugees (UNHCR) office in Mogadishu, Somalia, from October 15, 1979 to December 31, 1980, two Italian medical teams of the Associazione Universitaria per la Cooperazione Internazionale (AUCI) worked among the Ogaden Refugees in 3 camps of the Qorioley District, lower Shabelli Region of Somalia. Each team consisted of one physician and 2 registered nurses. The Qorioley district, about 140 km SW of Mogadishu, has high day-time temperatures and high humidity throughout the year. The day to night temperature gradients are high. Strong winds are blowing to and from the Indian Ocean.The 3 camps had been set up in the bush, on the right bank of the Shabelli river, about 8 km NW of Qorioley Town. The refugees in these camps were of Somali extraction and of Muslin culture and religion. They were housed in large military tents, aqal (round roofed skin covered hut of nomads), “mundul” (circular grass-thatched hut built around a central pole) and “arysh” (rectangular hut, corrugated iron tile roofs), aggregated at a very high density. More than 5000 people lived on one hectar. It was so crowded lhat there was no more space than 1.5 m2 of shelter per person. They lacked all hygienic services.Each camp had a food storage hut (mud walled with corrugated iron roof) and 2-3 water collection ponds, fed from the river. At the time of our arrival, two “arysh” with a total of 20 beds were in use for non-ambulatory patients. Scattered in the camps there were 6 “medical posts.”

Abstract Abstract 2478 Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. Approximately half of patients will be cured of their disease by primary therapy, including the R-CHOP regimen (rituximab, doxorubicin, cyclophosphamide, vincristine, desamethasone). The remaining die of the disease, mainly because of the occurrence of tumor drug resistance. Many efforts have been made to explain the biochemical and molecular mechanisms involved in resistance to the drugs used in the treatment of cancer patients, including those with DLBCL. A dose-intense therapy regimen (e.g. R-CHOP14) may help to improve the treatment outcome of DLBCL patients. We have carried out a retrospective study aimed at correlating the mRNA expression levels of genes involved in metabolism, mechanisms of action and resistance to doxorubicin (i.e. MDR1, GSTP1, TOPO-2a, Bcl-2, PKC-b2) that represents the backbone of the R-CHOP regimen with treatment outcome data of 54 patients at various stages of disease. The expression of the 5 above mentioned genes was determined in formalin-fixed paraffin-embedded samples from DLBCL using real time RT-PCR. A threshold analysis to identify a cut-off distinguishing recurrent or non-recurrent disease was used. The correlations between gene expression data and clinical/pathological characteristics as well as survival parameters have been evaluated by standard statistical tests. The case series included 32 males and 22 females; 6 patients had follicular lymphoma grade IIIb and 48 diffuse large B cell lymphoma; 19 presented symptoms at diagnosis. Thirty patients showed abnormal LDH values, the IPI was intermediate-high risk or high risk in 14 patients. Forty-six patients (85.2%) obtained a complete remission and 8 (14.8%) a partial response. The median overall survival (OS) as well as the median progression free survival (PFS) have not yet been reached after a median follow-up of 43.6 months. The mRNA expression levels of TOPO-2a and GSTP1 were detectable in all samples, that of PKC-b2 in 52 samples, that of MDR1 and bcl-2 in 34 and 29 samples, respectively. A high degree of interpatient variation in relative tumor expression of the study gene was observed: from 0.008 for TOPO-2a to >100.000 for PKCbII. Threshold analysis indicated significant inverse relationships between PKC-b2 and PFS (p=0.046): higher gene expression was associated with shorter PFS. Conversely, higher expression of ABCB1 was associated with prolonged PFS (p=0.039). This kind of analysis also showed associations between OS and TOPO-2a, GSTP1and PKC-b2: higher gene expression was associated with shorter OS. Overall, our results confirm that the high expression of some genes such as TopoIIa, GSTP1 and PKCβII may represent a prognostic factor in case of an intensified anthracycline-based chemotherapy with immunotherapy. Moreover, our results suggest that intensified immunochemotherapy could affect the role of bcl2, ABCB1, GSTP1 and TopoIIa in predicting tumor response. These results and others from related studies may help to identify gene profiles useful for selecting patients eligible for more intensified or personalized chemotherapy. Prospective larger studies are warranted. Supported by a grant from Associazione Giacomo Onlus, Castiglioncello (LI). Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2605 Poster Board II-581 Background. Annexin II (ANXA2) is a member of a peripheral membrane-binding protein family acting in a calcium-dependent manner, is involved in many cellular mechanisms, as cell proliferation and membrane physiology and is related to cancer progression. The aim of this study was to assess the ANXA2 expression in B cell precursor acute lymphoblastic leukemia (Bcp-ALL), in the attempt to finally evaluate it as a new potential therapeutic target. Materials and Methods. The ANXA2 expression was tested in 77 newly diagnosed pediatric Bcp-ALL diagnosed and treated in our centers, according with LLA-2000 protocol of Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP). Diagnostic samples and 3 B-ALL cell lines (REH, SEM, 697) were studied by reverse phase protein array (RPPA), western blot and real-time PCR (RQ-PCR) analyses. Furthermore, immunofluorescence on bone marrow smears and cytofluorimetric studies were performed, in order to visualize the protein subcellular location. The associations between the ANXA2 expression, molecular features and prognosis were evaluated. For statistical purpose, multivariate analyses with Wilcoxon test and t-Test with conservative Bonferroni corrections and Kaplan-Mayer analysis were performed. Pearson correlation was used to compare mRNA and protein levels. Results. Our analyses demonstrated a positive correlation between mRNA and protein ANXA2 expression (Pearson correlation or index 0.6). Comparing ANX2 expression and molecular features, we found a statistically significant difference between patients with unfavourable [t(9;22), t(4;11)] and favourable translocations [t(12;21)], showing a higher level of ANXA2 in the former group (p-value <0.05). Additionally ANXA2 resulted upregulated at both mRNA and protein levels in 24 out of 77 patients included in the study, and in the group presenting with high ANXA2 expression, 8 (33%) patients relapsed; in contrast, in the group with low ANXA2 expression only 8 out of 53 cases (15%) suffered from a relapse. Interestingly, 5 patients (21%) with high ANXA2 expression died of progressive disease, while with only one case (2%) in the group with low ANXA2 expression. A multivariate analysis also showed that ANXA2 is an independent predictor of disease's aggressiveness. Due to the heterogeneity of response to treatment among our patients, which imply a stratification based on detection of minimal residual disease (MRD), the correlation between high expression level of ANXA2 with prognosis resulted not statistically significant (Kaplan-Mayer p-value >0.05). However, our data strongly suggested a correlation with a worst prognosis in those cases with high ANXA2 expression. Furthermore, immunofluorescence and cytofluorimetric analyses performed on SEM and 697 cell lines showed that ANXA2 is localized on the cellular membrane's surface, where the protein is usually involved in many cell functions. Conclusions. To date, our study reports on ANXA2 expression and location in pediatric ALL. Our findings suggest that ANXA2 expression represents a marker of aggressiveness in Bcp-ALL, confirmed by the correlation with unfavourable molecular rearrangement such as MLL/AF4. Although the prognostic impact of ANXA2 expression needs to be evaluated with a further retrospective study including a larger and selected population, our data already strongly suggest that ANXA2 expression could be considered as a new potential therapeutic target in pediatric Bcp-ALL. Disclosures: No relevant conflicts of interest to declare.

Background: The project “Homeopathy for L’Aquila” was developed in order to provide humanitarian and professional assistance to the people of L’Aquila, who were the victims of a devastating earthquake during the night of April 6th, 2009. This project was promoted by the Federazione Italiana Associazioni Medici Omeopati (FIAMO) and supported by the governmental organization for Emergencies (Protezione Civile). Aim: This paper is the report of that experience in the state of absolute emergency, which lasted 17 months. It aims to be a feasibility study as well as a model for further emergencies. Methodology: A medical office was located in a container of 60 square meters which was open from Monday to Friday, beginning in August 2009 and lasting until December 2010. This was provided by Protezione Civile with all the basic equipment, including a reception with a secretary. There were 16 homeopathic physicians and 2 acupuncturists, coming from all over Italy. Every month they rotated to offer free consultations of Classical Homeopathy, as well as Acupuncture and Neuraltherapy. Only people coming from the earthquake area were admitted: all of them signed an informed consent. An operational protocol was defined for the data collection. Each consultation was reported in a special register. The follow-up period lasted 17 months. The protocol consisted of the first consultation and at least 3 control visits, when possible at 30, 60 and 120 day intervals. As a primary outcome the main complaint of the patient was considered in its relation to the quality of life. This evaluation followed a slightly modified criterion of a qualitative scale: Outcome in Relation to Impact on Daily Living (ORIDL). A statistical analysis with some non parametric tests was carried out (Kolmogorof, ). Even the most frequently prescribed homeopathic medicines were taken into consideration. Results: 674 patients were visited from August 2009 to December 2010. In total 1,542 medical visits and treatments were carried out (1,070 as Homeopathy; 280 as Neuraltherapy; 192 as Acupuncture). 366 patients received Classical Homeopathy. The most frequently treated syndromes were of the “psychiatric” type (162 cases=44%), prevalently due to the consequences of the earthquake, such as sleeping disturbances, phobic states, anxious-depressive syndromes, etc. The drop-outs were 235 out of 366 (=64%). 107 patients presented for a minimum 3 follow-ups. Here are the results: cured (52%), major improvement (33%), moderate and slight improvement (12%), no change (3%), deterioration (0%). The statistical analysis (D = 51 > 1,949; = 48,039 > 10,83) showed a significance higher than 1‰. Within this group, 68 patients suffering from psychiatric syndromes, who came for a 3rd follow up, showed a similar trend: cured (50%), major improvement (24%), moderate and slight improvement (19%), no change (7%), deterioration (0%). Also in this case the statistical analysis indicated a significance higher than 1‰ (D = 30 > 1,949). The most frequently prescribed medicines were Pulsatilla, Sepia, Arsenicum Album, Argentum Nitricum and Lycopodium. Discussion: The numerous inconveniences due to the emergency certainly did not permit the usual control visits. Moreover a strict observance of the protocol was not always possible, which could explain such a high number of drop-outs. Those patients who completed the therapy had an incremental improvement in their health between the 1st and the 3rd follow-up visit. In the final analysis a series of “strengths” and “weaknesses” in the project were noted. This knowledge could be helpful for future emergencies. Conclusions: The project “Homeopathy for L’Aquila” allowed, for the first time in Italy, an official implementation of Homeopathy in an emergency plan of great impact, on the one hand; and, on the other hand, made a precious human and professional experience possible. Moreover the results obtained have demonstrated that Homeopathy can play an important role socially as well as therapeutically. To the present date there have neither been internationally recognized guidelines nor publications with similar data concerning emergencies. Therefore this project could represent an important reference point for similar events.

Abstract Introduction: Standard chemotherapy represented by the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen is successful in about 60% of patients (pts) with diffuse large B-cell lymphoma (DLBCL). Pts who do not benefit from this treatment, due to the development of tumor drug resistance, have a very poor prognosis. Currently, knowledge on reasons of treatment related failures in DLBCL are scanty and predictive biomarker of response are largely unknown. We hypothesized that polymorphisms of gene involved in the pharmacokinetics and pharmacodynamics of drugs included in R-CHOP regimen may play a role in predicting the outcome in DLBCL pts.Thus, we designed a multicentre prospective pharmacogenetic trial aimed at identifying gene polymorphisms potentially predictive of drug efficacy/resistance in DLBCL pts treated with R-CHOP. An interim analysis on the first 80 enrolled ptswas planned and has been performed. Methods: The study included chemonaive DLBCL pts at various stages of disease candidate to an R-CHOP standard treatment. The Ethical Committee of each participating centre approved the pharmacogenetic protocol, and all pts signed a written informed consent. According to the aims of this interim analysis, the impact of single nucleotide polymorphisms (SNPs) on R-CHOP efficacy was evaluated by objective response (OR) rate at the end of treatment. The efficacy of R-CHOP was evaluated according to the Cheson criteria by performing standard hematochemical and instrumental (TC and FDFG-PET) tests and defining complete remission (CR), partial remission (PR), non response or progressive disease (PD). Genomic DNA wasextracted from peripheral blood of 80 pts. Twentysingle nucleotide polymorphisms (SNPs) from18candidate genes (ABCB1, ABCC1, ABCC2, ABCG2, CYBA, CYP2C9, FCGR2A, GSTP1, IL2, MLH1, NCF4, NQO1, NQO2, RAC2, TNF, TOP2A, TP53, TUBB)involved in pharmacokinetics and pharmacodynamics of R-CHOP (www.pharmgkb.org) have been analysed by a genotyping array based on Affimetrix methodology. Univariate analysis was performed to evaluate associations between polymorphisms and clinical/pathological characteristics or OR (Fisher exact test). Multivariate logistic regression analysis was performed to estimate adjusted odds ratios along with the corresponding 95% confidence intervals for the polymorphisms and OR. Results: Median age was 63 years. There were 37 men and 43 women. 47.5 % of pts were in stage I-II,52.5 % of pts in stage III-IV. 27.5% of ptshad bulky disease, 43.8 % of pts had involvement of extranodal site. 47.5% of pts had pathological LDH value. According to the revised IPI, 15 % pts were in the low risk group, 58.7 % in the intermediate risk group, and 26.3 % in the high risk group.Overall, 468 courses of R-CHOP had been administered (mean: 5.85 courses, range: 4-6). 81% of pts had CR to R-CHOP whereas the remaining showed PR (14%) or PD(5%). No statistically significant correlation was found between OR and clinical characteristics of pts.However, stage III-IV pts showed a worst OR than stage I-II pts (77% vs 87% of CR, respectively); pts with bulky disease had worst OR than non-bulky disease pts(73% vs 84.5% of CR, respectively); ptswith R-IPI 3-5 a worst OR than pts with R-IPI 0-2 (71.5% vs 85% of CR, respectively). Univariate and multivariateanalysis identified TOPOII rs13695as a predictor of OR (p=0.042). Pts with CT or TT genotypesshowed worst OR than CC wild-type homozygous pts (odds ratio 3.070, CI95% 1.113-13.457). Also, a statistical trend toward significance was observed for MLH1 rs1800734 polymorphism (p=0.062): ptswith homozygous genotype for the mutant allele showed a better OR than wild-type and heterozygous pt genotypes. Conclusions: No significant relationship between clinical/pathological characteristics and OR was observed. Our preliminary data show that SNPs affecting a gene involved in doxorubicin pharmacodynamics, i.e. the drug target TOPOII, as well asone of the major components of DNA mismatch repair, i.e. MLH1 gene,may predict response in DLBCL pts treated with R-CHOP. These preliminary results from the interim analysis are promising and warrant completion of pt accrual to reach the planned number of cases at the end of our study. Acknowledgments This work was supported by a grant from the Associazione Giacomo Onlus, Castiglioncello (LI), Italy to E.M. and Cassa di Risparmio di Firenze, Firenze, Italy to S.N. Disclosures No relevant conflicts of interest to declare.

2013/2014
Il sistema uditivo è uno degli organi sensoriali più complessi e coinvolge cellule ciliate, neuroni cocleari, e molti altri elementi regolati da basi molecolari. L'analisi genetica dei tratti complessi/malattie come la funzione uditiva e la presbiacusia potrebbe far luce su questi meccanismi molecolari. Fino ad ora solo pochi geni sono noti per contribuire alla variabilità della funzione uditiva. Capirla dal punto di vista genetico può essere molto interessante e può anche fornire indizi importanti per individuare le cause genetiche della presbiacusia. La questione è di fondamentale importanza per la nostra società che invecchia sempre più. La presbiacusia è la perdita sensoriale più diffusa negli anziani e colpisce il 30 % delle persone di età superiore ai 60 anni. La malattia non dà direttamente pericolo di vita, ma contribuisce alla perdita di autonomia ed è associata all'ansia, alla depressione e alla perdita di funzioni cognitive che compromettono seriamente la qualità della vita. Inoltre, le interazioni con fattori ambientali dovrebbero essere prese in considerazione. Per tenere conto di questi fattori, ci siamo concentrati su popolazioni isolate, dove le persone condividono lo stesso ambiente e occupazioni/abitudini analoghe. L'obiettivo principale della tesi è la comprensione delle basi molecolari della variazione della funzione uditiva utilizzando: a) Genome-Wide Association Studies (GWAS) per identificare nuovi geni/loci; b) l'associazione statistica per replicare i candidati identificati; c) studi di espressione per valutare il ruolo dei candidati nella coclea di topo. In primo luogo abbiamo replicato 9 geni precedentemente pubblicati (CSMD1, ANK2, CDH13, DCLK1, ARSG, EVI5, GRM8, RIMBP2, SLC16A6) con un’analisi di associazione per geni candidati nella coorte della Silk Road (SR) che comprende diverse comunità isolate nel Caucaso e in Asia centrale. In seguito, una grande collaborazione con la coorte britannica TwinsUK ha portato ad una nuova meta-analisi di GWAS, in cui abbiamo identificato uno SNP significativo nel gene SIK3. Infine, con la disponibilità dei dati del progetto 1000Genomes per l’imputazione, un’ulteriore meta-analisi ci ha permesso di individuare altri due loci vicino ai geni PCDH20 e SLC28A3, che siamo stati in grado di replicare in due coorti indipendenti dal Regno Unito (B58C) e dalla Finlandia (FITSA). Tutti i geni identificati sono risultati espressi nella coclea. Per quanto riguarda contributi originali alla metodologia GWAS, abbiamo sviluppato un pacchetto R chiamato MultiMeta. Si tratta di un metodo statisticamente efficace per eseguire la meta-analisi in un contesto multivariato, con un approccio flessibile e strumenti per gestire facilmente la visualizzazione dei risultati. Il metodo può essere applicato a qualsiasi insieme di risultati multivariati e sarà molto utile per analizzare i dati uditivi e possibilmente per individuare nuove associazioni, sfruttando la correlazione tra fenotipi.
The auditory system is one of the most complex sensory organs, involving hair cells, cochlear neurons and many other components, strongly regulated by the underneath molecular bases. The genetic analysis of complex traits/diseases such as normal hearing function (NHF) and Age-Related Hearing Loss (ARHL) could shed light on these molecular mechanisms. Until now, only few genes are known to contribute to the variability of NHF. Understanding NHF from the genetic point of view can be very interesting and also provide important clues to solving ARHL genetic causes. This issue is of fundamental importance for our ageing society. In fact, Age-Related Hearing Loss is the most prevalent sensory impairment in the elderly affecting 30% of people aged over 60. The disease is not directly life threatening but it contributes to loss of autonomy and is associated with anxiety, depression, and cognitive decline largely compromising the quality of life. Moreover, interactions with lifestyle and environmental determinants should be taken into account. In order to overcome these confounding factors, we focused on isolated populations, where people share the same environment and similar occupations/habits. The main aim of the thesis is the understanding of the molecular bases of variation of normal hearing function using: a) Genome Wide Association Studies (GWAS) to identify new genes/loci; b) Statistical association to replicate new candidate findings; c) expression studies to evaluate their role in the mouse cochlea. Firstly we replicated 9 previously published genes (CSMD1, ANK2, CDH13, DCLK1, ARSG, EVI5, GRM8, RIMBP2, SLC16A6) by running a candidate association analysis in the Silk Road cohort (SR) including several isolated communities in Caucasus and Central Asia. Afterwards a large collaboration with the TwinsUK cohort led to a GWAS meta-analysis, which identified a significant SNP in SIK3 gene. Finally, with the availability of 1000Genomes Project imputation data another GWAS meta-analysis allowed us to identify two more loci close to PCDH20 and SLC28A3 genes, which we were able to replicate in two independent cohorts from UK (B58C) and Finland (FITSA). All the identified genes were expressed in mouse cochlea. As regards new contribution in GWAS methodology, we developed an R package software called MultiMeta. It is a novel statistically efficient method to perform meta-analysis in a multivariate setting with a flexible approach and tools for easily visualizing results. The method can be applied to any multivariate set of results and will be very useful for analysing hearing data and hopefully leading to novel association discovery, by taking into account the underlying correlations between phenotypes.
XXVII Ciclo
1987

L’Agenda Digitale Europea stabilisce il ruolo chiave delle tecnologie dell’informazione e della comunicazione (TIC) grazie a un mercato digitale unico basato su internet veloce e superveloce e su applicazioni interoperabili, al fine di ottenere vantaggi socioeconomici sostenibili COM(2010)245. Le TIC producono un'innovazione di prodotto e cambiamenti strutturali all'interno di tutto il sistema economico e possiamo affermare che dal punto di vista multisettoriale hanno un ruolo moltiplicativo sulla crescita economica, poiché l’aumento della domanda di TIC stimola a sua volta tutte le altre produzioni. Inoltre come riscontrato in letteratura economica, nelle istituzioni internazionali, nonché confermate dai dati periodici rilasciati dagli uffici statistici nazionali, una maggiore incidenza della popolazione attiva formalmente istruita in associazione con l'adozione delle TIC è altamente correlata ad una crescita robusta, sostenibile ed equa. In questo quadro è importante valutare il ruolo delle TIC nel sistema economico, in particolare verrà analizzato il ruolo delle TIC sia rispetto ad un particolare settore quello della sanità, che dal lato dei soggetti che dovrebbero essere parte attiva nella gestione delle TIC ovvero la situazione delle abilità digitali dei lavoratori dipendenti. Il primo articolo si focalizza sul ruolo delle TIC nella determinazione dell’output del settore sanitario, utilizzando il database WIOD (World Input Output Database), di 24 paesi nell’arco temporale 2000-2014, tenendo conto anche dei differenti sistemi sanitari nazionali. La produzione del settore “Sanità e Servizi Sociali” assume, almeno in alcuni paesi specifici, il ruolo di stimolo all’innovazione che compensa ampiamente quello di peso sul bilancio pubblico. Nel secondo articolo analizziamo come l’uso delle TIC stia progressivamente aumentando nel sistema sanitario italiano e in particolare come l'introduzione del Fascicolo Sanitario Elettronico (FSE), strumento di condivisione dei dati sanitari del singolo cittadino, potrebbe determinare cambiamenti nella produzione sui servizi sanitari. Verranno analizzati gli eventuali cambiamenti strutturali dei processi produttivi e della produzione totale applicando l'Analisi Strutturale di Decomposizione (SDA). La base dati di riferimento sarà la tavola di Input-Output riferita a due diversi periodi al fine di individuare i risultati sia degli effetti tecnologici sia della domanda finale a livello settoriale. Infine l’ultimo articolo ha l’obiettivo di valutare le conseguenze dei cambiamenti nella composizione dell'occupazione per competenza digitale all’interno del flusso di produzione e distribuzione del reddito. Verrà costruita una Matrice di Contabilità Sociale (SAM) che consente di rappresentare le relazioni tra i cambiamenti di produzione delle attività e i cambiamenti di compensazione dei dipendenti per competenze, grado di digitalizzazione e genere. LA SAM sviluppata nel documento è relativa all'Italia nel 2013; il lavoro è disaggregato in competenze formali / non formali / informali e, inoltre, competenze digitali / non digitali. Le abilità digitali del lavoro seguono la definizione di “competenza formale” della Commissione Europea (2000): i) competenza formale a seconda del livello di istruzione e formazione; ii) competenza non formale acquisita sul posto di lavoro e attraverso le attività delle organizzazioni e dei gruppi della società civile; iii) competenza informale non acquisita intenzionalmente durante la vita. In questo quadro è stata introdotta un'ulteriore classificazione di input di lavoro basata sull'uso / non utilizzo di computer collegati a Internet. Sulla base della SAM, è stato implementato un modello multisettoriale esteso. Infine, verrà individuata una struttura adeguata di domanda finale che consente di ottenere i migliori risultati in termini di valore aggiunto distribuiti a lavoratori più qualificati con una elevata competenza digitale.