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L'articolo espone le riflessioni che scaturiscono da una decisione giudiziale del Tribunale per i minorenni di Firenze in tema di diritto alla conoscenza delle origini esercitato nei confronti dei fratelli. L'intervento rappresenta un contributo alla riflessione su un tema certamente controverso, come evidenzia la presenza di una decisione di segno diverso di cui pure sono sinteticamente richiamate le motivazioni, di fronte al quale, nel perdurante silenzio del legislatore, i tribunali minorili sono chiamati ad esercitare una complessa ponderazione delle diverse posizioni soggettive implicate nelle decisioni.

// Fiamma Buttitta 1 , 2 , 3 , Lara Felicioni 3 , Alessia Di Lorito 2 , Alessio Cortellini 4 , Luciana Irtelli 5 , Davide Brocco 5 , Pietro Di Marino 5 , Donatella Traisci 6 , Nicola D’Ostilio 6 , Alessandra Di Paolo 7 , Francesco Malorgio 7 , Pasquale Assalone 8 , Sonia Di Felice 9 , Francesca Fabbri 9 , Giovanni Cianci 9 , Michele De Tursi 2 , 5 and Antonio Marchetti 1 , 2 , 3 1 Laboratory of Diagnostic Molecular Oncology, Center for Advanced Studies and Technology (CAST), University of Chieti, Chieti, Italy 2 Department of Medical and Oral Sciences and Biotechnologies, University of Chieti, Chieti, Italy 3 Department of Pathology, SS Annunziata Clinical Hospital, Chieti, Italy 4 Department of Oncology, San Salvatore Hospital, L’Aquila, Italy 5 Department of Oncology, SS Annunziata Clinical Hospital, Chieti, Italy 6 Department of Oncology, Floraspe Renzetti Hospital, Lanciano, Italy 7 Department of Oncology, Spirito Santo Hospital, Pescara, Italy 8 Department of Oncology, “S.S. Giovanni Paolo II” Veneziale Hospital, Isernia, Italy 9 Department of Oncology, Giuseppe Mazzini Hospital, Teramo, Italy Correspondence to: Antonio Marchetti, email: amarchetti@unich.it Keywords: epidermal growth factor receptor ( EGFR ); tyrosine-kinase Inhibitors; circulating tumor-DNA (ct-DNA); massive parallel sequencing (MPS); resistance-inducing mutation Received: January 08, 2020 Accepted: February 17, 2020 Published: March 17, 2020 ABSTRACT In Non-Small-Cell Lung Cancer (NSCLC) patients treated with Tyrosine Kinase-Inhibitors (TKIs) therapy, the emergence of acquired resistance can be investigated by plasma monitoring of circulating tumor DNA (ctDNA). A series of 116 patients with EGFR -positive lung adenocarcinomas were treated with first/second generation EGFR TKIs. At clinical progression, 64 (55%) EGFR T790M plasma positive patients were subjected to second line-treatment with osimertinib and strictly monitored during the first month of therapy. Plasma analysis by the EGFR Cobas test showed in 57 (89%) cases a substantial decrease in the levels of the sensitizing EGFR mutant allele (s EGFR ma), down to a not detectable value. These patients were defined as plasmatic good responders (PGR). In 7 (11%) patients, the s EGFR ma did not drop to zero (plasmatic poor responders, PPR). In these latter cases, Massive Parallel Sequencing (MPS) analysis at the end of the first month and at clinical progression showed the presence of resistant-inducing mutations, including MET and HER2 gene amplification, KRAS and PIK3CA gene mutations. PPR showed disease progression in 5 (71%) cases, stable disease in 2 (29%) cases, and a shorter median Progression-free survival (PFS) (4.3 ± 1.1 months) than that observed in PGR (13.3 ± 1.2 months) ( P < 0.0001). Our data indicate that plasma monitoring by a simple RT-PCR-based EGFR mutation test in the first month of treatment may be useful for a rapid identification of patients to be subjected to further characterization by MPS. A diagnostic algorithm for an early detection of resistance-inducing mutations and patient management is reported.

Multiple left ventricular pacing strategies have been suggested for improving response to cardiac resynchronization therapy (CRT). However, these programming strategies may sometimes entail accepting configurations with high pacing threshold and accelerated battery drain. We assessed the feasibility of predefined pacing programming protocols, and we evaluated their impact on device longevity and their cost-impact. We estimated battery longevity in 167 CRT-D patients based on measured pacing parameters according to multiple alternative programming strategies: single-site pacing associated with lowest threshold, non-apical location, longest interventricular delay, and pacing from two electrodes. To determine the economic impact of each programming strategy, we applied the results of a model-based cost analysis using a 15-year time horizon. Selecting the electrode with the lowest threshold resulted in a median device longevity of 11.5 years. Non-apical pacing and interventricular delay maximization were feasible in most patients and were obtained at the price of a few months of battery life. Device longevity of > 10 years was preserved in 87% of cases of non-apical pacing and in 77% on pacing at the longest interventricular delay. The mean reduction in battery life when the second electrode was activated was 1.5 years. Single-site pacing strategies increased the therapy cost by 4–6%, and multi-site pacing by 12–13%, in comparison with the lowest-cost scenario. Modern CRT-D systems ensure effective pacing and allow multiple optimization strategies for maximizing service life or for enhancing effectiveness. Single- or multi-site pacing strategies can be implemented without compromising device service life and at an acceptable increase in therapy cost.

In Italy, during the second epidemic wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapid antigenic (Ag) test at point-of-care (POCT) station were employed to quickly evaluate large numbers of swabs. We collected data of all children who underwent the Ag test in our hospital. All positive patients were recalled to perform reverse transcription polymerase chain reaction. A total of 2133 tests were collected over 1 month. Clinical data of 1941 children (median age = 3.7 years) were analyzed: 1343 (69.2%) patients complained of symptoms, 594 (30.6%) had a history of close contact with SARS-CoV-2-positive individuals. Among symptoms reported, acute rhinitis was the most frequent (67.9%), followed by cough (42.6%) and fever (31.5%). Among all tests, 95.8% resulted negative, 4.2% positive: 37/89 were confirmed. In confirmed cases, fever (56.2% vs 32.2%; P = .041) and gastrointestinal symptoms (18.8% vs 6.25%; P = .041) were significantly more frequent compared with negative children. The use of POCT for Ag test seems appropriate for SARS-CoV-2 screening in the pediatric population. In children, fever and gastrointestinal symptoms may constitute red flags of SARS-CoV-2.

In 1848 Adele Schopenhauer chose Denmark and Iceland as the setting for what was to become her last novel, a text written almost entirely under the sunny skies of the Roman Campagna. In its long descriptions of the Scandinavian landscapes the text expresses the fascination the Northern territories exerted on the German public throughout the nineteenth century and thus offers a real voyage of the mind as an alternative to the sunny and soothing southern destinations.

Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of care in the management of advanced non–small cell lung cancer (NSCLC). Nevertheless, only a small proportion of patients benefit from ICIs. The aim of the present study is to assess whether 2-deoxy-2-[18F]fluoro-D-GLUCOSE POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY ([18F]FDG-PET/CT)–derived parameters may be used as biomarkers in patients with advanced NSCLC receiving first-line pembrolizumab. Materials and methods: This is a monocentric retrospective cohort study including patients with advanced NSCLC (stage IV) and Programmed death-ligand 1 (PD-L1) expression ≥50% treated with pembrolizumab. A control group of patients treated with epidermal growth factor receptor (EGFR) inhibitors for EGFR-mutated NSCLC was also enrolled. Only patients with a positive [18F]18F-FDG PET/CT result within 60 days from treatment initiation were included.Total metabolic tumour volume (tMTV) was calculated for each lesion using a dedicated software (PET VCAR; GE Healthcare), which semiautomatically delineates the tumour's contours with a maximum standardised uptake value (SUVmax) threshold of 42% within the lesion. tMTV was obtained summing each lesion's MTV. Potential prognostic parameters for overall survival (OS) were analysed (tMTV, SUVmax, bone/liver metastasis, neutrophil:lymphocyte ratio ≥4, Eastern Cooperative Oncology Group performance status ≥2, lactate dehydrogenase above the upper limit of normal). Results: Overall, 34 patients treated with first line-pembrolizumab and 40 patients treated with EGFR tyrosine kinase inhibitors were included. In the pembrolizumab group, the median follow-up was 20.3, while the median OS was 4.7 months (95% confidence interval [CI] = 0.3–9.1) for patients with tMTV ≥75 cm3 vs not reached (NR) for patients with tMTV

PURPOSE: Cancer clinical trials (CTs) are now more complex than ever before and require dedicated personnel (clinical research coordinators [CRCs]) to perform regulatory and administrative activities and protocol- and patient-related procedures. We developed a simple tool to measure the workload (WL) of CRCs involved in cancer research and to estimate personnel requirements within a Clinical Trial Center. METHODS: A literature review and 2-month period in which CRCs recorded their activities in a diary provided valuable information that led to the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Workload Assessment Tool (IWAT) being divided into three sections: Protocol, On-Treatment Patients, and Follow-Up Patients. Twelve full-time senior CRCs from three sites of the Network measured their monthly WL for 30 months to evaluate IWAT reproducibility and accuracy. RESULTS: The IWAT proved to be a user-friendly tool (3-6 minutes required for each CT), with high reproducibility (interobserver reproducibility ranged from 82% to 100% for each IWAT item). In December 2017, the Network had 185 ongoing CTs, with a median of 2.5 active centers for each CT. On the basis of 448 total IWAT measures by CRCs, the majority of trials were academic (57%) or dealt with advanced disease (77%). The median IWAT WL score for each study was 20.98 ± 22.90 (range, 2-188) and 475 ± 229 (range, 150 [junior staff] - 930 [extreme heavy WL]) for each CRC. On the basis of our experience, a monthly WL score of 500-600 was considered an appropriate value for a full-time CRC. CONCLUSION: The IWAT could prove useful in evaluating CT complexity, estimating appropriate CRC WLs, and defining personnel requirements. Independent validation by other CRCs working in different organizational contexts and in different countries is needed.

In Non-Small-Cell Lung Cancer (NSCLC) patients treated with Tyrosine Kinase-Inhibitors (TKIs) therapy, the emergence of acquired resistance can be investigated by plasma monitoring of circulating tumor DNA (ctDNA). A series of 116 patients with EGFR-positive lung adenocarcinomas were treated with first/second generation EGFR TKIs. At clinical progression, 64 (55%) EGFR T790M plasma positive patients were subjected to second line-treatment with osimertinib and strictly monitored during the first month of therapy. Plasma analysis by the EGFR Cobas test showed in 57 (89%) cases a substantial decrease in the levels of the sensitizing EGFR mutant allele (sEGFRma), down to a not detectable value. These patients were defined as plasmatic good responders (PGR). In 7 (11%) patients, the sEGFRma did not drop to zero (plasmatic poor responders, PPR). In these latter cases, Massive Parallel Sequencing (MPS) analysis at the end of the first month and at clinical progression showed the presence of resistant-inducing mutations, including MET and HER2 gene amplification, KRAS and PIK3CA gene mutations. PPR showed disease progression in 5 (71%) cases, stable disease in 2 (29%) cases, and a shorter median Progression-free survival (PFS) (4.3 ± 1.1 months) than that observed in PGR (13.3 ± 1.2 months) (P < 0.0001). Our data indicate that plasma monitoring by a simple RT-PCR-based EGFR mutation test in the first month of treatment may be useful for a rapid identification of patients to be subjected to further characterization by MPS. A diagnostic algorithm for an early detection of resistance-inducing mutations and patient management is reported.

BACKGROUND: In 2014 we identified a new subset of DLBCL, defined as "IgM-secreting" (Cox MC & Di Napoli A , PLOS One 2014). This was characterised by poor prognostic features and outcome as well as frequent central nervous (CNS) system localizations. Furthermore, IgM-secretion, was an independent prognostic factor in multivariate analysis. Here we report on the largest series of IgM-secreting-DLBCL, from a multicentre Italian study. METHODS: The observational and biological study was approved by the Ethical Committee of the AUO Sant'Andrea, Italy. Enrolment criteria were: DLBCL with an associated IgM paraprotein diagnosed between 1st January 2010 and 31st December 2018 (IgM-secreting). Data were collected both prospectively and retrospectively from 17 Centres participating in the study. In addition, histopathology samples were centrally revised for immunohistochemistry (IHC) and FISH analyses. The control group (CTRL) consisted in a series of consecutive DLBCL, without an associated IgM-paraprotein (diagnosed between 01/01/2013 and 30/06/2016, enrolled in the Lymphoma Registry of the Lazio region (ReLLi Network). Last follow-up was carried out on 31st December 2019. RESULTS: 569 DLBCL cases were enrolled: 102 (17.9%) were IgM-secreting; 48 (8.4%) had a non-IgM paraprotein (IgA, IgG, or other), and 414 (72.7%) had no associated paraprotein (CTRL). IgM-secreting cases within the consecutive DLBCL patients enrolled in the ReLLi Registry were 41/466 (8.8%, 95CI 6.4-11.7%) while non IgM-paraprotein DLBCL cases were 11/466 (2.4%, 95CI 1.2-4.2%). The median level of IgM paraprotein was 17gr/L (range: 60 (p=.001); 2] advanced stage (pUNL (p=.008) ; 5] ≥2 Extra-nodal sites involved (p60, B-symptoms, bulky disease, IPI >low risk and IgM-secreting IgM showed a worse survival (all with p CONCLUSION: Our data confirm that IgM-secreting DLBCL: 1) represents a sizable proportion of non-DH DLBCL; 2) have poor prognostic features and 3) have mostly a non-GC phenotype. Furthermore, IgM secretion appears to be an independent prognostic factor for both PFS and OS. Studies to define the biological features of this new subset are ongoing. Disclosures Cantonetti: Mundipharma: Consultancy; Takeda: Consultancy; Vifor: Consultancy; Roche: Consultancy. Re:BerGenBio ASA: Research Funding. Abruzzese:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria.

Metronomic-chemotherapy (M-CHT) has been rarely assessed in non-Hodgkin-lymphoma (NHL). Therefore, in 2011 we started experimenting a new all-oral M-CHT schedule termed DEVEC (Deltacortene®, etoposide, vinorelbine, cyclophosphamide, +/-Rituximab) in diffuse-large-B-cell lymphoma (DLBCL) patients. Methods Patients with stage Ib-IV were enrolled as follows: 1) treatment-naive, frail ≥65y, or unfit ≥85y; and 2) relapsed/refractory (R/R) ≥55y. Data were prospectively collected from six Italian centres and compared for efficacy to two reference groups, treated with established iv Rituximab-CHT in 1st and 2nd line respectively. Results from April-2011 to March-2018, 17/51(33%) naive, 21/51(41%) refractory and 13/51(25.5%) relapsed patients started DEVEC; 39/51(76.5%) were de-novo DLBCL; 10/51(19.6%) transformed-DLBCL and 2/51(3.9%) unclassifiable-DLBCL/classical-Hodgkin-lymphoma. The median age was 85y (range=77-93) and 78y (range=57-91) in naive and R/R respectively and overall the DEVEC patients had very poor features compared to the reference. The rate of grade≥3 haematological-AEs was 43%(95CI=29-58%): G3-neutropenia was the most frequent; grade≥3 extra-haematological-AEs was 13.7% (95%CI=5.4-25.9%), the most frequent was infection. One-year OS and PFS were 67% and 61% for naive, 60% and 50% for reference-naive respectively; Cox proportional hazard ratio (Cox-PH-ratio) for OS and PFS were 0.69 (95%CI=0.27-1.76;p=.441) and 0.68 (95%CI=0.28-1.62;p=.381) respectively. One-year OS and PFS were 48% and 39% in the R/R, 36% and 17% in the reference-R/R respectively; Cox-PH-ratio for OS and PFS, were 0.76 (95%CI=0.42-1.40; p=.386) and 0.48 (95%CI=0.28-0.82; p=.007) respectively. Conclusion The favourable activity of DEVEC compared to a real-life series and the convenience of an oral administration, may possibly lay the groundwork for a paradigm-shift in the treatment of elderly DLBCL.

The compensation of executive board members in Germany has become a highly controversial topic since Vodafone's hostile takeover of Mannesmann in 2000 and it is again in the spotlight since the outbreak of the financial crisis of 2009. Based on unique panel data evidence of the 500 largest firms in Germany in the period 1977-2009 we test two prominent hypothesis in the literature on executive pay: the manager power hypothesis and the efficient pay hypothesis. We find support for the manager power hypothesis for Germany as executives tend to be rewarded when the sector is doing well rather than the firm they work for. We reject, however, the efficient pay hypothesis as CEO pay and the demand for managers increases in Germany in difficult times when the typical firm size shrinks. We find further that domestic and global competition for managers has contributed to the rise in executive pay in Germany. Lastly, we show that CEOs in the banking sector are provided with incentives for performance and that the great recession of 2009 acted as a disciplining devise on CEO pay in Germany.

Patients with solid cancer frequently develop bone metastases (BM). Zoledronic acid (Zometa®, ZA), routinely used to treat patients with BM, acts on osteoclasts and also has antitumor properties. We aimed to assess the effect of ZA over time in novel bone turnover markers (RANK/receptor activator of nuclear factor-k B ligand (RANK-L)/ Osteoprotegerin (OPG)) and to correlate these with serum N-terminal telopeptide (NTX). The study prospectively evaluated levels of RANK, RANK-L and OPG transcripts by real-time PCR and NTX expression by ELISA in the peripheral blood of 49 consecutive patients with advanced breast, lung or prostate cancer. All patients received the standard ZA schedule and were monitored for 12 months. Median baseline values of RANK, RANK-L and OPG were 78.28 (range 7.34–620.64), 319.06 (21.42–1884.41) and 1.52 (0.10–58.02), respectively. At 12 months, the median RANK-L value had decreased by 22% with respect to the baseline, whereas median OPG levels had increased by about 96%. Consequently, the RANK-L/OPG ratio decreased by 56% from the baseline. Median serum NTX levels decreased over the 12-month period, reaching statistical significance (p < 0.0001). Our results would seem to indicate that ZA modulates RANK, RANK-L and OPG expression, thus decreasing osteoclast activity.

7563Background: Metronomic chemotherapy (MC) is an emerging approach in solid tumours. Since MC has been poorly investigated in aggressive lymphomas in 2011, we formulated a new oral MC regimen ter...

Using data from the British Labour Force Survey this article provides an empirical investigation of the way immigration affects labour market outcomes of native born workers in Britain, set beside a theoretical discussion of the underlying economic mechanisms. We discuss problems arising in empirical estimation, and how to address them. We show that the overall skill distribution of immigrants is remarkably similar to that of the native born workforce. We find no strong evidence that immigration has overall effects on aggregate employment, participation, unemployment and wages but some differences according to education.

In this paper we investigate economic activity of female immigrants and their husbands in Britain. We distinguish between two immigrant groups: foreign born females who belong to an ethnic minority group and their husbands, and foreign born females who are white and their husbands. We compare these to native born white women and their husbands. Our analysis deviates from the usual mean analysis and investigates employment, hours worked and earnings for males and females, as well as their combined family earnings, along the distribution of husbands' economic potential. We analyse the extent to which economic disadvantage may be reinforced on the household level. We investigate to what extent disadvantage can be explained by differences in observable characteristics. We analyse employment assimilation for all groups over the migration cycle. Our main results are that white female immigrants and their husbands are quite successful, with an overall advantage in earnings over white native born both individually and at the household level. On the other hand, minority immigrants and their husbands are less successful, in particular at the lower end of the husband's distribution of economic potential. This is mainly due to low employment of both genders, which leads to disadvantage in earnings, intensified at the household level. Only part of this differential can be explained by observable characteristics. Over the migration cycle, the data suggests that employment differentials are large at entry for white immigrant females, and even larger for minority females, but the gap to the native born closes. Assimilation is more rapid for white females.

49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome characterized by mental retardation, severe speech impairment, craniofacial abnormalities, multiple skeletal defects, and genital abnormalities. We describe a 13-year-old boy with 49,XXXXY syndrome, language impairment, seizures, and left-hemisphere magnetic resonance imaging abnormalities and review the distinctive neurologic, cognitive, and behavioral phenotypes associa t e d w i t h t h i s d i s o r d e r. F i n a l l y, w e d i s c u s s testosterone supplementation in the treatment of this syndrome. ( J Child Neurol 2003;18:501—504).

Do multinational firms exhibit different patterns of labor demand from purely domestic firms? Many standard models of trade and multinational companies suggest such differences. We examine this question using a plant-level panel covering U.K. manufacturing from 1973 through 1992, where we can distinguish U.K.-headquartered multinationals, foreign-owned multinationals, and domestic U.K. firms. Across these three ownership groups we look for differences both on the intensive margin, in terms of labor-demand elasticities, and on the extensive margin, in terms of plant shutdowns. For our sample period we estimate that both groups of multinational plants had larger increases than did domestic plants in the elasticity of demand for production labor. These increases were driven largely by greater substitutability between production labor and materials. We also estimate that both types of multinational plants are more likely to shut down than domestic plants are, conditional on a set of operational advantages enjoyed by multinationals that make them less likely to shut down.

In this retrospective study, we evaluated the chromogranin A (CgA) baseline value as a predictor of clinical outcome in patients with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone 1000 mg per day, whose disease progressed after docetaxel chemotherapy. In the 48 evaluable patients, serum CgA level was normal when n=16), within three times the upper normal value (UNV) when between 120 and 360 (group B, n=16), more than three times the UNV when ≥360 ng/ml (group C, n=16). Decline in PSA level ≥50% or more (PSA RR) was observed in 26 of 48 (54%) patients. PSA response rate did not correlate with the CgA groups. CgA levels more than three times the UNV predicted an early radiological progressive disease in eight of 11 cases (73%). The median progression-free survival (PFS) among the CgA groups A, B, and C was 9.2, 9.2, and 4.8 months respectively, P=0.0459. The median overall survival (OS) among the CgA groups was 19.0, 18.8, and 10.8 months respectively, P=0.2092. In the multivariate analysis, PSA RR (nonresponsive vs responsive) and CgA levels (group 3 vs groups 1+2) were predictors of PFS (P=0.0002 and P=0.0047 respectively), whereas PSA RR only was significantly associated with OS (P=0.0024), while CgA levels remained of borderline significance (P=0.0919). A serum CGA level more than three times the UNV predicted PFS and showed a trend vs OS prediction, independently from PSA response, in CRPC patients treated with abiraterone.

Author Summary Background. Recent evidence shows that use of anthracycline and taxane adjuvant chemotherapy and dose-dense regimens, consisting of more frequent administration of the drugs, have improved outcomes for breast cancer patients. In this study, we evaluated administration of an epirubicin-based regimen with paclitaxel in a sequential, dose-dense schedule as adjuvant treatment for patients with high-risk primary breast cancer. Methods. In a phase II Simon two-stage design study, we evaluated the feasibility of a modified fluorouracil, epirubicin, and cyclophosphamide (FEC) regimen at high dose intensity (fluorouracil 500 mg/m2 i.v. on days 1 and 4, epirubicin 60 mg/m2 i.v. on days 1 and 4, and cyclophosphamide 500 mg/m2 i.v. on days 1 and 4; all drugs were administered every 14 days for 3 cycles) with granulocyte colony-stimulating factor support followed by dose-intense weekly paclitaxel 100 mg/m2 for 8 cycles. In 11 patients with breast cancer following quadrantectomy (n = 8) or modified radical mastectomy (n = 3), any grade 3 (G3) or higher nonhematologic toxicity (excluding alopecia, nausea or vomiting, and bone pain, which might be a consequence of the administration of filgrastim) and adherence to the scheduled dose-dense treatment (deliverability) were monitored with the purpose of enrolling an additional 27 patients in the case of a satisfying toxicity profile and deliverability of the planned treatment (at least 7 patients completing the treatment). Results. Five of 11 patients experienced G3 or higher nonhematologic toxicity during the FEC regimen. We did not observe G3 or higher nonhematologic toxicity related to paclitaxel treatment. In particular, three patients experienced G3 fatigue, one patient had G3 oral mucositis, three patients had G3 hypokalemia, one patient had G3 syncope, one patient had G3 transaminitis (alanine aminotransferase), one patient experienced G4 pulmonary thromboembolism, and 1 patient had a G3 breast infection. Four of 11 patients received the regimen with a 25% dose reduction of day 1 and 4 administrations of FEC. Seven of 11 patients required FEC delay ≥7 days in at least 1 cycle, regardless of dose intensity. Two patients failed to complete the FEC regimen. Two of the remaining 9 patients were treated with paclitaxel delay ≥7 days in at least one cycle. After a median follow-up of 28 months, 9 patients were continuously disease free. Conclusion. The tolerability rate of a dose-density regimen with FEC followed by weekly paclitaxel was considered not promising for completing the accrual of this study.

Background: Older (age ≥60 years) patients with acute myeloid leukemia (AML) have poor outcomes and intensive induction chemotherapy is frequently unsuitable. Thus, new safe and effective therapies are urgently needed. Tosedostat, a new, orally bioavailable inhibitor of members of the M1 and M17 classes of aminopeptidases, was proven to be effective in both de novo and relapsed AML. We hypothesize that the addition of tosedostat to cytarabine may improve the response rate and remission duration over what is expected with chemotherapy or tosedostat alone. Methods: This was a phase II, prospective, multicenter study, designed according to Fleming's method. Fixing the lowest acceptable rate as 10% and the successful rate as 25%, with a significance level alpha=0.05 and a power 1-beta =0.80, the sample size was estimated in 33 patients. Thirty-three patients (median age 75 years) received Tosedostat 120 milligrams orally once daily until disease progression, coupled with intermittent low-dose cytarabine given subcutaneously at 20 milligrams twice/day for 10 days. Courses of cytarabine were repeated every 4 weeks in the absence of disease progression or unacceptable toxicity, up to 8 cycles. Global gene expression profiling (GEP, Affymetrix Human Gene 2.0 Array) was performed on purified AML blasts of 29 patients from peripheral blood or bone marrow at diagnosis before treatment initiation. Unsupervised clustering was generated using a hierarchical algorithm based on the average-linkage method. Principal component analysis (PCA) and supervised gene expression analysis was performed by using GeneSpring GX 12.0 (Agilent, USA). Results: The characteristic of enrolled patients are listed in table 1 Induction-period mortality was 12%, with 4 deaths occurring in aplasia. According to intent-to-treat, the CR rate was 48.5% (16/33 patients); 2 additional patients obtained a partial response, for an overall response rate of 54.6%. In addition, 4/33 patients remained in stable disease for a median time of 9 months (range: 4-14). Seven patients did not respond and died with progressive disease after having received a median of 2 cycles of cytarabine and 45 days of tosedostat. In responding patients, the median time to best response was 74 days (range 22-145). Responding patients (CR+PR) had a longer median overall survival than non-responders (P=0.018). Six out of 18 (33%) responding patients are still in CR after a median follow-up of 425.5 days (range 208-758); 5 additional patients are alive with stable disease. Twenty-two patients died [while in aplasia (4), in CR (1), due to resistant disease (9) or due to progressive disease (8) after a median CR duration of 192 days (87-535)]. 29 patients had GEP analysis, and a molecular signature associated with the clinical response (CR vs. no CR) was identified. By supervised analysis, 212 genes differentially expressed based on the clinical response (complete remission (CR) vs no CR) were identified (Mann-Whitney, p2). The 212 genes differentially expressed were significantly associated with six relevant biological functions and pathways: β-catenin (βcat); TNFα signaling pathway via NFκB; ERB2; STK33/SKM (serine/threonine kinase 33 expression using the SKM cell line); inflammatory response; and epithelial-mesenchymal transition pathways. Conclusions: The tosedostat and low-dose cytarabine combo produced a CR rate superior to what expected (45.4% versus 25%), and thus met the primary endpoint of study. Further, potential biomarkers were identified by GEP. Specifically, the achievement of CR could be efficiently predicted by the gene expression patterns with an overall accuracy exceeding 90%. A validation analysis is currently being conducted on additional 14 patients in order to confirm the ability of GEP to identify potential responders to TST. The study was registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) n.2012-000334-19. Acknowledgments: CTI is gratefully acknowledged for providing Tosedostat for the patients. The study was supported in part by AIL Pesaro Onlus. Table 1. Characteristic N = 33 Median age, years (range) 75 (62-85) Median WBC count, × 109/L (range) 3.05 (0.26-24.53) Blasts, % (range) 60 (20-96) Cytogenetic risk group*, n Not evaluable 3 (9%) Intermediate Karyotype 17 (52%) Unfavourable Karyotype 13 (39%) AML, n De novo 16 (48%) Secondary, n 17 (52%) Disclosures Fanin: Novartis Farma: Speakers Bureau.

In this paper, we analyse the association between the spatial concentration of ethnic minorities and racial harassment. Ethnic concentration relates to racial harassment through at least three channels: hostility in the attitudes of majority individuals that finds expression in harassment behaviour, the probability that minority individuals meet majority individuals, and the cost of expressing hostility aggressively. Thus, harassment cannot simply be modelled as a stronger form of hostility. Using unique data for Britain, we show that, in areas of higher local ethnic concentration, experience of harassment is lower, even though hostility on the side of the majority population is not.

In this paper, we analyse the association between spatial concentration of ethnic minorities, and racial harassment. Ethnic concentration relates to racial harassment through at least three channels: hostility in attitudes of majority individuals that find expression in harassment behaviour, the probability of minority individuals meeting majority individuals, and the cost of expressing hostility aggressively. Harassment can thus not simply be modeled as a stronger form of hostility. Using unique data for Britain, we show that, in area of higher local ethnic concentration, experience of harassment is lower, even though hostility on the side of the majority population is not.

The main objective of this paper is to provide a comprehensive description of the economic outcomes and performance of Britain's immigrant communities today and over the last two decades. We distinguish between males and females and, where possible and meaningful, between immigrants of different origins. Our comparison group is white British-born individuals. Our data source is the British Labour Force Survey. We first provide descriptive information on the composition of immigrants in Britain, and how this has changed over time, their socio-economic characteristics, their industry allocation and their labour market outcomes. We then investigate various labour market performance indicators (labour force participation, employment, wages and self-employment) for immigrants of different origins, and compare them with British-born whites of the same age, region and other background characteristics. We find that over the last 20 years, Britain's immigrant population has changed in origin composition and has dramatically improved in skill composition — not dissimilar from the trend in the British-born population. We find substantial differences in economic outcomes between white and ethnic minority immigrants. Within these groups, immigrants of different origins differ considerably with respect to their education and age structure, their regional distribution and their sector choice. In general, white immigrants are more successful in Britain, although there are differences between groups of different origins. The investigation shows that immigrants from some ethnic minority groups, and in particular females, are particularly disadvantaged, with Pakistanis and Bangladeshis at the lower end of this scale.

BACKGROUND. Ifosfamide (IFO) and cisplatin (CDDP) are active drugs in the treatment of patients with squamous cell carcinoma (SCC) of the head and neck. 13-Cis retinoic acid (RA), along with its antiproliferative and differentiating activity on SCC cell lines, has immunomodulatory and chemopreventive effects. The objective of the current Phase I‐II study was to evaluate the combination of CDDP, IFO, and RA in patients with advanced or recurrent SCC of the head and neck. METHODS. Patients with measurable recurrent, metastatic, or locally advanced SCC of the head and neck were eligible. Patients received a fixed dose of 20 mg/m 2 CDDP, and IFO was administered with sodium mercaptoethanesolfonate in threedose increments (1000 mg/m 2 , 1200 mg/m 2 , and 1500 mg/m 2 ) up to dose limiting toxicity. Both drugs were given for 5 consecutive days every 3 weeks. RA (0.5 mg/kg) was given orally for 5 days per week. RESULTS. Fifty-two patients either with locoregional recurrence or distant metastases (50%) or with locally advanced SCC of the head and neck beyond surgery or radiation therapy (50%) were entered into the trial. Fifteen patients were enrolled in the Phase I study, during which the maximum tolerated dose of IFO was 1500 mg/m 2 . In the Phase II study (CDDP 20 mg/m 2 and IFO 1200 mg/m 2 ), the response rate was 72% (95% confidence interval, 57‐ 83%). After a median follow-up of 23 months, the median time to disease progression was 10.4 months (range, 2.9 ‐ 47.21 months), and the median overall survival was 12.95 months (range, 1.7‐ 47.21 months). Two patients were converted from a partial response to a complete response with RA. Toxicity was relatively well tolerated and caused no deaths. Grade 3‐ 4 neutropenia was observed in 16 patients, and Grade 2‐3 diarrhea toxicity occurred in 9 patients. CONCLUSIONS. The dose and schedule for the combination of CDDP, IFO, and RA that were used in this study are feasible and active in the treatment of patients with SCC of the head and neck, with durable responses and a relatively well tolerated toxicity. Cancer 2001;92:814 ‐21. © 2001 American Cancer Society.

This paper uses two recent UK surveys to investigate labour market performance, the determinants of language proficiency, and the effect of language on earnings and employment probabilities of non-white immigrants. Our results show that language acquisition, employment probabilities, as well as earnings differ widely across non-white immigrants, according to their ethnic origin. Language has a strong and positive effect on employment probabilities. Furthermore, lack of English fluency leads to substantial earnings losses for immigrants. While earnings of white and ethnic minority natives develop in a similar manner, there is a large earnings gap between these two groups, and ethnic minority immigrants. English fluency contributes considerably to reducing these differences. Addressing the problems of measurement error and unobserved heterogeneity in language variables, our results indicate that measurement error in the language variable leads to underestimation of the importance of language for employment probabilities and earnings in straightforward regressions. In comparison with results found for other countries, language proficiency seems to be more important for labour market outcomes of UK immigrants.

134 Background: In this prospective study, in patients with CRPC previously treated with docetaxel, we evaluated prostate specific antigen (PSA) and FCH-PET/CT for early response assessment to abiraterone acetate, and assessed frequency of early FCH-PET/CT discordant with PSA and clinical response. Methods: Twenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was repeated after 4-6 weeks and a CT scan was done after 3 months of abiraterone acetate. FCH-PET/CT bone flare was defined as the combination, after 3 months of therapy, of an interpreting radiologist’s report indicating progressive disease (PD) in context of a ≥50% decline in PSA, no PD at 3-month CT scan, with FCH-PET/CT improvement or stability 2-3 months later. Results: Three of 29 patients treated with abiraterone acetate did not perform the follow-up FCH-PET/CT due to rapidly PD with a decline in performance status. Of the remaining 26 patients, 4 are still undergoing early response evaluation. Twenty two pts, median age was 71 yrs (range, 57-86 yrs) were evaluable for this analysis. A ≥50% PSA decline was observed in 15/22 (68%) evaluable pts. Undetectable PSA levels (≤0.1 ng/mL) occurred in one case. Early FCH PET/CT response assessment was as follows: complete response (n=2, 9%), partial response (n=7, 32%), stable disease (n=3, 14%), PD (n=10, 45%), but in 4 of 10 pts with PD a bone flare phenomenon on FCH PET/CT was observed. PSA decline ≥50% and FCH PET/CT response correlated in 19 of 22 pts (86%). Conclusions: Discordant findings between serologic PSA response and increases in early FCH-PET/CT bone lesion intensity are reported here for the first time in CRPC. Further investigation is needed to clarify the confounding effect of FCH-PET/CT bone flare on patient management and interpretation of results.

10615 Background: Bone metastasis disrupts bone integrity through loss of the balance between osteoclastic-mediated osteolysis and osteoblastic osteogenesis. The RANK/RANK-L/OPG axis governs osteoclastogenesis and bone resorption. We evaluated the trend of markers over time. Secondary aims were to study the predictive role of different circulating markers in the response to Zoledronic Acid (ZA) with respect to objective response and to skeletal-related events (SREs). Methods: The study prospectively evaluated levels of RANK, RANKL and OPG transcripts by Real-Time PCR and VEGF and NTX expression by ELISA in the peripheral blood of 49 consecutive patients with advanced breast, prostate or lung cancer (36, 7 and 6, respectively). Enrolled patients were at first diagnosis of bone metastases and had not previously undergone treatment with bisphosphonates. Patients received the standard schedule of ZA (4 mg infusion every 28 days) for about 12 months, undergoing blood tests and instrumental evaluation before the first infusion of ZA and every 4 months thereafter. Results: Median RANKL values after 12 infusions of ZA had decreased by 22% with respect to baseline whereas OPG, had increased by about 96%, with a 56% decrease in the RANKL/OPG ratio. NTX decreased over time (p

The lively artistic exchange of marble objects between Liguria and the French Provence that took place throughout the Baroque age had its centre of distribution in Genoa and its centre of reception in Marseille. Various sculptors from both regions travelled to and from the two parts of the Mediterranean, looking for new artistic conditions and working opportunities. Artistic biography of Honore Pelle has to be seen in this context. Born in 1641 in the French Dauphine region, he moved to Genoa in 1672, most likely after a period of apprenticeship in Rome. In Genoa he put up a flourishing workshop that produced sculpture for the local nobility and clergy as well as for the great European courts. In the artistic climate strongly influenced by the works of Pierre Puget, Pelle distinguishes himself with a production in various materials (marble, wood, bronze) that emphsizes the surfaces and recalls the model of classical Rome.

// Ugo De Giorgi 1 , Paola Caroli 2 , Salvatore L. Burgio 1 , Cecilia Menna 1 , Vincenza Conteduca 1 , Emanuela Bianchi 1 , Francesca Fabbri 3 , Elisa Carretta 3 , Dino Amadori 1 , Giovanni Paganelli 2 , Federica Matteucci 2 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS, Meldola, Italy 2 Department of Nuclear Medicine, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS, Meldola, Italy 3 Biostatistics and Clinical Trials Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS, Meldola, Italy Correspondence to: Ugo De Giorgi, e-mail: ugo.degiorgi@irst.emr.it Keywords: Abiraterone, Castration-resistant prostate cancer, 18F-fluorocholine positron emission tomography, PSA, Bone flare Received: August 13, 2014 Accepted: October 01, 2014 Published: October 11, 2014 ABSTRACT Objective: We investigated the role of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in the early evaluation of abiraterone and outcome prediction in patients with metastatic castration-resistant prostate cancer (CRPC). Patient and methods: Forty-three patients with metastatic CRPC progressing after docetaxel received abiraterone 1,000 mg daily with prednisone 5 mg twice daily. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was done at baseline and after 3 to 6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). Results: Declines in PSA level of ≥50% were seen in 21 of 43 (49%) patients. Forty-two patients were evaluable for FCH-PET/CT response. FCH-PET/CT bone flare was observed in 4 of 42 (10%) evaluable patients. In univariate analysis, PSA decline and FCH-PET/CT response predicted PFS, while PSA decline and FCH-PET/CT (progression vs non progression) predicted OS. In multivariate analysis, only FCH-PET/CT (progression vs nonprogression) remained significant for PFS and OS ( p = 0.022 and p = 0.027, respectively). Conclusion: Early FCH-PET/CT can predict clinical outcome in CRPC beyond PSA response. These data support further studies on FCH-PET/CT for abiraterone monitoring and outcome prediction in patients with CRPC.

Living Archives perform a function of social memory sharing, which contributes to building social bonds, communities, and identities. This potential lays in the ability of Living Archives to put together an archival function, which allows with the conservation and transmission of memory, with an artistic, performative and creative function linked to the present. As part of the DARE-UIA (Digital environment for colaborative alliances to regenerate urban ecosystem in middle-sized cities) project, the creation of a living digital archive made possible to create a narrative that would consolidate the cultural memory of the Darsena district of the city of Ravenna. The aim of the project is to stimulate the urban regeneration of a suburban area of a city, enhancing its cultural memory and identity heritage, through digital heritage tools. The methodology used involves various digital storytelling actions necessary for the overall narrative using georeferencing systems (GIS), storymaps and 3D reconstructions for a transversal narration of historical content such as personal and institutional historical photos and to enhance the industrial archeology heritage of the neighborhood. The aim is the creation of an interactive and replicable narrative in similar contexts to the Darsena district in Ravenna. The Living Archive, in which all the digital contents are inserted, finds its manifestation towards the outside with the form of a museum spread throughout the neighborhood, making the contents usable on smartphones via QR codes and totems inserted on-site, creating thematic itineraries spread around the neighborhood. The construction of an interactive and engaging digital narrative has made possible to enhance the material and immaterial heritage of the neighborhood by recreating the community that has historically always distinguished it., Bibliothecae.it, Vol. 11 No. 2 (2022)