Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874]

BACKGROUND: High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. METHODS: Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m(2)/d intravenously (IV) 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m(2)/d IV 5 days/week × 4 weeks followed by 10 MU/m(2 )subcutaneously (SC) three times per week × 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. RESULTS: The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m(2)/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m(2)/week) (p = 0.003). CONCLUSION: Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited

Influence of apical oxygen on the extent of in-plane exchange interaction in cuprate superconductors

In high Tc superconductors the magnetic and electronic properties are determined by the probability that valence electrons virtually jump from site to site in the CuO2 planes, a mechanism opposed by on-site Coulomb repulsion and favored by hopping integrals. The spatial extent of the latter is related to transport properties, including superconductivity, and to the dispersion relation of spin excitations (magnons). Here, for three antiferromagnetic parent compounds (single-layer Bi2Sr0.99La1.1CuO6+delta, double-layer Nd1.2Ba1.8Cu3O6 and infinite-layer CaCuO2) differing by the number of apical atoms, we compare the magnetic spectra measured by resonant inelastic x-ray scattering over a significant portion of the reciprocal space and with unprecedented accuracy. We observe that the absence of apical oxygens increases the in-plane hopping range and, in CaCuO2, it leads to a genuine 3D exchange-bond network. These results establish a corresponding relation between the exchange interactions and the crystal structure, and provide fresh insight into the materials dependence of the superconducting transition temperature.Comment: 9 pages, 4 figures, 1 Table, 42 reference

Extending the Belavin-Knizhnik "wonderful formula" by the characterization of the Jacobian

A long-standing question in string theory is to find the explicit expression of the bosonic measure, a crucial issue also in determining the superstring measure. Such a measure was known up to genus three. Belavin and Knizhnik conjectured an expression for genus four which has been proved in the framework of the recently introduced vector-valued Teichmueller modular forms. It turns out that for g>3 the bosonic measure is expressed in terms of such forms. In particular, the genus four Belavin-Knizhnik "wonderful formula" has a remarkable extension to arbitrary genus whose structure is deeply related to the characterization of the Jacobian locus. Furthermore, it turns out that the bosonic string measure has an elegant geometrical interpretation as generating the quadrics in P^{g-1} characterizing the Riemann surface. All this leads to identify forms on the Siegel upper half-space that, if certain conditions related to the characterization of the Jacobian are satisfied, express the bosonic measure as a multiresidue in the Siegel upper half-space. We also suggest that it may exist a super analog on the super Siegel half-space.Comment: 15 pages. Typos corrected, refs. and comments adde

PhenoWorld : a new paradigm to screen rodent behavior

Modeling depression in animals has inherent complexities that are augmented by intrinsic difficulties to measure the characteristic features of the disorder. Herein, we describe the PhenoWorld (PhW), a new setting in which groups of six rats lived in an ethological enriched environment, and have their feeding, locomotor activity, sleeping and social behavior automatically monitored. A battery of emotional and cognitive tests was used to characterize the behavioral phenotype of animals living in the PhW and in standard conditions (in groups of six and two rats), after exposure to an unpredictable chronic mild stress paradigm (uCMS) and antidepressants. Data reveal that animals living in the PhW displayed similar, but more striking, behavioral differences when exposed to uCMS, such as increased behavioral despair shown in the forced swimming test, resting/sleep behavior disturbances and reduced social interactions. Moreover, several PhW-cage behaviors, such as spontaneous will to go for food or exercise in running wheels, proved to be sensitive indicators of depressive-like behavior. In summary, this new ethological enriched paradigm adds significant discriminative power to screen depressive-like behavior, in particularly rodent's hedonic behavior

Breast lesion classification based on absorption and composition parameters: a look at SOLUS first outcomes

A machine learning classification algorithm is applied to the SOLUS database to discriminate benign and malignant breast lesions, based on absorption and composition properties retrieved through diffuse optical tomography. The Mann-Whitney test indicates oxy-hemoglobin (p-value = 0.0007) and lipids (0.0387) as the most significant constituents for lesion classification, but work is in progress for further analysis. Together with sensitivity (91%), specificity (75%) and the Area Under the ROC Curve (0.83), special metrics for imbalanced datasets (27% of malignant lesions) are applied to the machine learning outcome: balanced accuracy (83%) and Matthews Correlation Coefficient (0.65). The initial results underline the promising informative content of optical data

Initial examples of the SOLUS multimodal potential

We present initial evidence of the SOLUS potential for the multimodal non-invasive diagnosis of breast cancer by describing the correlation between optical and standard radiological data and analyzing a case study

TNF-α is involved in activating DNA fragmentation in skeletal muscle

Intraperitoneal administration of 100 μg kg−1 (body weight) of tumour necrosis factor-α to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-α-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-α-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-α receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-α partly mediates DNA fragmentation during experimental cancer-associated cachexia

SOLUS: An innovative multimodal imaging system to improve breast cancer diagnosis through diffuse optics and ultrasounds

To improve non-invasively the specificity in the diagnosis of breast cancer after a positive screening mammography or doubt/suspicious ultrasound examination, the SOLUS project developed a multimodal imaging system that combines: B-mode ultrasound (US) scans (to assess morphology), Color Doppler (to visualize vascularization), shear-wave elastography (to measure stiffness), and time domain multi-wavelength diffuse optical tomography (to estimate tissue composition in terms of oxy- and deoxy-hemoglobin, lipid, water, and collagen concentrations). The multimodal probe arranges 8 innovative photonic modules (optodes) around the US transducer, providing capability for optical tomographic reconstruction. For more accurate estimate of lesion composition, US-assessed morphological priors can be used to guide the optical reconstructions. Each optode comprises: i) 8 picosecond pulsed laser diodes with different wavelengths, covering a wide spectral range (635-1064 nm) for good probing of the different tissue constituents; ii) a large-area (variable, up to 8.6 mm2) fast-gated digital Silicon Photomultiplier; iii) the acquisition electronics to record the distribution of time-of-flight of the re-emitted photons. The optode is the basic element of the optical part of the system, but is also a stand-alone, ultra-compact (about 4 cm3) device for time domain multi-wavelength diffuse optics, with potential application in various fields

SOLUS: a novel multimodal approach to ultrasound and diffuse optics imaging of breast cancer

A multimodal instrument for breast imaging was developed, combining ultrasound (morphology), shear wave elastography (stiffness), and time domain multiwavelength diffuse optical tomography (blood, water, lipid, collagen) to improve the non-invasive diagnosis of breast cancer