516 research outputs found

    Synergy of multispectral and multisensors satellite observations to evaluate desert aerosol transport and impact of dust deposition on inland waters: study case of Lake Garda

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    The capabilities of different Earth Observation multispectral satellites are employed for detecting and tracking of desert dust coming from North Africa toward the Northern Italy area and for evaluating the impact of Saharan dust deposition in inland waters, such as those of Lake Garda. Absorbing and scattering spectral optical properties of desert aerosol in the atmospheric windows in the ultraviolet, visible-near-infrared, and infrared spectral ranges are exploited in the dust retrieval performed by OMI/Aura, MODIS/Terra-Aqua, and SEVIRI/MSG satellite sensors. Therefore, the direct link between dust deposition and increase in phytoplankton abundance has been assessed retrieving MERIS-based chlorophyll-a (chl-a) concentration for the desert dust events. Estimates of the increased chl-a in the lake have been derived with values in concentration from 30% to 170%. AERONET sun-photometer measurements, gravimetric particulate matter samplings

    Biological Characteristics and Medical Treatment of Breast Cancer in Young Women—A Featured Population: Results from the NORA Study

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    Background. The present paper described the biological characteristics and clinical behavior of young women in the cohort NORA study Patients and Methods. From 2000–2002, patients (N > 3500) were enrolled at 77 Italian hospitals. Women aged ≤50 years (N = 1013) were stratified into age groups (≤35, 36–40, 41–45, and 46–50 years). The relationship between age and patient characteristics, cancer presentation, and treatment was analyzed. Results. Younger women more frequently had tumors with ER/PgR-negative(χ2 = 7.07; P = .008), HER2 amplification (χ2 = 5.76; P = .01), and high (≥10%) Ki67 labelling index (χ2 = 9.53; P = .002). Positive nodal status, large tumors, and elevated Ki67 all associated with the choice for chemotherapy followed by endocrine therapy in hormone receptor-positive patients (P < .0001). At univariate analysis, ER-ve status, chemotherapy and age resulted as the only statistically significant variables (HR = 2.02, P = .004, and >40 versus ≤40, P < .0001, resp.). At multivariate analysis, after adjustment for significant clinical and pathological factors, age remains a significant prognostic variable (HR = 0.93, P = .0021). Conclusion. This cohort study suggests that age per sè is an important prognostic factor. The restricted role of early diagnosis and the aggressive behavior of cancer in this population make necessary the application of targeted medical strategies crucial

    Technological behavior of porcelain stoneware bodies with Egyptian syenites

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    The progressive depletion of the main feldspathic flux deposits in the World is forcing the ceramic industry to search for suitable substitutes. The aim of this study is to assess the potential of some feldspar sources in the Egyptian Eastern Desert, particularly syenites from Abu Khruq, in the manufacture of ceramic tiles. Beneficiated samples obtained by laboratory-scale mineral processing were tested into porcelain stoneware batches (from 10% to 30% wt in replacement of feldspars) and compared with a reference body through a laboratory reproduction of the industrial processing. The technological behavior of unfired tiles does not suffer any significant alteration due to the use of syenites. On the other hand, syenite-bearing bodies exhibit some changes in the phase composition and the chemistry of the melt, that turns richer in alkali, especially K2O. The consequently increased sintering rate depends mainly on the viscosity of the liquid phase formed during firing. In conclusion, syenites can be used without technological hindrances to manufacture porcelain stoneware tiles. The firing behavior of syenite-bearing batches can be reasonably adjusted by setting key parameters (eg, the feldspar amount and the Na/K ratio), but the darker color of fired bodies requires to further lower the iron oxide

    γ-Catenin-Dependent Signals Maintain BCR-ABL1<sup>+</sup> B Cell Acute Lymphoblastic Leukemia.

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    The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ-catenin in the initiation and maintenance of BCR-ABL1 &lt;sup&gt;+&lt;/sup&gt; B-ALL but not CML. The selectivity was explained by a partial γ-catenin dependence of MYC expression together with the susceptibility of B-ALL, but not CML, to reduced MYC levels. MYC and γ-catenin enabled B-ALL maintenance by augmenting BIRC5 and enforced BIRC5 expression overcame γ-catenin loss. Since γ-catenin was dispensable for normal hematopoiesis, these lineage- and disease-specific features of canonical Wnt signaling identified a potential therapeutic target for the treatment of BCR-ABL1 &lt;sup&gt;+&lt;/sup&gt; B-ALL

    The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

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    CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

    Attitude towards active surveillance: A cross-sectional survey among patients with uroandrological disorders

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    Objectives We looked at subjective attitude towards active surveillance (AS) as the first option for cancer management in a cohort of patients seeking first medical help for uroandrological disorders prior to a formal discussion with a caregiver. Design Cross-sectional observational study. Setting Uroandrological outpatient clinic of a European academic centre. Participants Data of 1059 patients at their first access for uroandrological purposes from January 2014 to December 2016 were analysed. Intervention Patients were invited to complete a survey with closed questions investigating their attitude towards AS, prior to any clinical evaluation. Likewise, patients were invited to score the importance given to different aspects of personal life in the case of a cancer diagnosis, using a 10-point Likert scale. Primary and secondary outcomes measures The reported opinion towards AS management for cancer was assessed. Logistic regression analyses tested participants' sociodemographic characteristics associated with a positive opinion on AS. Results Positive, negative and doubtful attitudes towards AS were observed in 347 (33%), 331 (31%) and 381 (36%) patients, respectively. Female patients were more likely to report a negative attitude towards AS (38.7% vs 29.6%, p=0.04) while patients with previous parenthood more frequently reported a positive opinion on AS (37.2% vs 29.9%, p=0.005). Patient age emerged as the only predictor of a positive attitude towards AS (OR 1.03; 95% CI 1.01 to 1.04, p<0.001), with a 46% and 33% probability of being pro-AS for a patient aged 65 and 45 years, respectively. Conclusions One out of three patients would express positive feedbacks on AS in the unfortunate case of tumour diagnosis, only according to his/her baseline personal opinion and prior to any discussion with a cancer caregiver. The older the patient, the higher the probability of being compliant with a conservative management for cancer

    A computational approach to identify whole genome homozygosity mapping across multiple SNP mapping experiments

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    The recent development of microarray platforms, capable to genotype more than thousands of single nucleotide polymorphisms (SNPs) in individuals, had provided an opportunity to rapidly identify susceptibility loci for complex phenotypes. High density SNP mapping arrays have been widely applied to association studies, to copy number (CN) analysis in cancers and recently to investigate the role of homozygosity extended regions in individuals. Long stretches of CN neutral and homozygous SNPs, defined as runs of homozygosity (ROHs) can be found either in a single individual or shared across samples. The identification of ROHs among affected individuals of the same family or among unrelated ones with same disease, can underline loci potentially implicated in the genetic basis of the disease under study. Therefore the identification of ROHs in affected individuals or pathological datasets gives a chance to identify disease associated loci and new causative mutations. In order to identify ROHs pattern across Affymetrix SNP mapping datasets, we developed a computational strategy including several computational steps: 1) loss of heterozygosity analysis by dChip2007 software; 2) a within-subject step allowing the identification of ROHs in a single sample; 3) an across-subject step extracting the ROH fingerprint of the dataset and 4) the identification of a common ROHs pattern based on frequency across the dataset under study, varying the number of individuals carrying common ROHs; 5) the annotation step allowing the association of genes to selected ROHs. In order to obtain an effective ROHs visualization, we use dChip software for the entire samples dataset. We assess our strategy to two SNP mapping datasets including 100K leukemia and 250K congenital recessive diseases. The procedure allowed the identification of a unique genetic ROH fingerprint of clinical datasets potentially important to discover new diseases associated loci suitable for further investigations

    Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial

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    Background: Thymidine kinase 1 (TK1) is an enzyme downstream of the CDK4/6 pathway, with a critical role in DNA synthesis; serum TK1 activity (sTKa) is a novel liquid biopsy biomarker of tumour cell proliferation. Methods: The phase IIIb, BioItaLEE trial (NCT03439046) collected sera from postmenopausal patients with hormone receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) treated with first-line ribociclib plus letrozole at baseline, day 15 of cycle 1 (C1D15), day 1 of cycle 2 (C2D1), and at first imaging. Associations between sTKa assessed at different time points or sTKa dynamic patterns, and progression-free survival (PFS) were evaluated using multivariate Cox models. Results: Overall, 287 patients were enroled. Median follow-up was 26.9 months. High sTKa (>median) at baseline was associated with higher risk of progression (hazard ratio [HR], 2.21; 95% confidence interval [95% CI], 1.45, 3.37; P = 0.0002); similar results were observed for patients with high sTKa levels at C1D15 and C2D1. Early sTKa dynamic patterns were strongly predictive of PFS. The pattern with high sTKa levels at C2D1 following initial decrease at C1D15 was associated with higher risk of progression versus the pattern with low sTKa levels at both time points (HR, 2.89; 95% CI, 1.57, 5.31; P = 0.0006), while the pattern with high sTKa levels at C1D15 was associated with the shortest PFS (HR, 5.65; CI: 2.84, 11.2; P < 0.0001). Baseline and dynamic sTKa changes provided independent information. Conclusions: sTKa appears to be a new promising prognostic and pharmacodynamic biomarker in patients with HR+/HER2– ABC treated with ribociclib plus letrozole as first-line therapy
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