Lo sviluppo sostenibile: Societa', territorio ed azione

Nonostante per molto tempo si sia fatto riferimento al territorio come elemento di riferimento fondamentale nei processi di sviluppo economico e sociale, il viaggio nei luoghi del Cilento e dl Vallo di Diano potrebbe convincerci che la "nozione di spazio" deve essere rivisitata fino a mettere completamente in discussione il concetto di "luogo" come fattore che determina i processi sociali. La diversita' delle situazioni esistenti invita ad aprire piuttosto che restringere il concetto di divisione nello spazio delle attivita'; in tale nuova prospettiva vengono messi in discussione i modelli che spiegano le divisioni con la semplice appartenenza a norme e valori comuni (identita' storico culturale e potenzialita' dei luoghi). Si tratta di ricercare una contrapposizione dialettica tra modelli culturali (o i modelli) che vedono la societa' come una stratificazione di diversi subsistemi risultanti da diversi tipi di attivita' (vocazione territoriale) e modelli che propongono l'azione come aspetto creativo dell'attivita' umana e non si accontentano del modello adattivo. In tal senso, l'azione dell'uomo diviene il momento centrale di riferimento per definire le attivita' possibili che daranno valenze diverse allo spazio (territorio). La contrapposizione tra i due modelli ha una duplice finalita': la prima di carattere pedagogico per esporre il metodo di lavoro e di ricerca, l'altra di mantenere il carattere scientifico della proposta cioe' un'ipotesi teorica da sottoporre a test (casi studio di applicazione della metodologia). Sebbene la nozione di azione potrebbe apparire poco definita essa deve essere vista come direzione che si sostanzia in processi specifici senza una specificazione ex-ante. Eventi o progetti vengono riconosciuti strategicamente necessari in quanto rilevanti per il cambiamento del modello di fruizione delle risorse sul territorio (spazio nuovo). L'approccio metodologico che si cerchera' di proporre richiede uno sforzo concettuale perche' ipotizza che sia possibile descrivere la realta' senza necessariamente separare gli aspetti materiali da quelli mentali (immateriali)e da quelli socio culturali

Knowledge Economy and Regional Innovation Policy Milieu

The emergence of the knowledge economy has resulted in a new definition of regional policy milieu. Under the current EU policy framework the concepts of region and city are the result of an inductive, exploratory cognitive process. Interpreting, assessing and designing successful territorial milieux constitute a methodological challenge for analysts. This paper discusses the methodological capacity of a hybrid theoretical approach to discovery and design of smart specialization. Analysis of strategic network formation (why the network takes a particular form) demonstrates the competitive positioning of specific homogeneous communities within the global value chain and can be considered central to the regional policy milieu. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabella normale"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;

Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram

IntroductionIdentifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations.Patients and methodsWe retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation.ResultsA total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36–0.91, p 0.02) and number of metastatic sites (<3 vs ≥3, HR 0.68, 95% CI 0.48-0.98, p 0.04). After splitting albumin value at the median (3.84 g/dL), a score system was capable of stratifying patients in 3 groups with significantly different OS (p<0.0001). Relationship with OS reproduced in the external cohort (p=0.008). Then, from these factors we built a nomogram.ConclusionsPrior treatment, serum albumin and number of metastatic sites are readily available prognostic traits in patients with advanced malignancies participating into immunotherapy early-phase trials. Combination of these factors can optimize patient selection at study enrollment, maximizing therapeutic intent

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9-related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes

Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial

Background Results from small randomised trials on tamoxifen in the treatment of hepatocellular carcinoma (HCC) are conflicting, We studied whether the addition of tamoxifen to best supportive care prolongs survival of patients with HCC. Methods Patients with any stage of HCC were eligible, irrespective of locoregional treatment. Randomisation was centralised, with a minimisation procedure accounting for centre, evidence of disease, and time from diagnosis. Patients were randomly allocated best supportive care alone or in addition to tamoxifen, Tamoxifen was given orally, 40 mg per day, from randomisation until death. Results 496 patients from 30 institutions were randomly allocated treatment from January, 1995, to January, 1997. Information was available for 477 patients. By Sept 15, 1997, 119 (50%) of 240 and 130 (55%) of 237 patients had died in the control and tamoxifen arms, respectively. Median survival was 16 months and 15 months (p=0.54), respectively, No differences were found within subgroups defined by prognostic variables. Relative hazard of death for patients receiving tamoxifen was 1.07 (95% CI 0.83-1.39). Interpretation Our findings show that tamoxifen is not effective in prolonging survival of patients with HCC

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection