The onset and solidification path of a basaltic melt by in situ differential scanning calorimetry (DSC) and ex situ investigations

The in situ differential scanning calorimetry (DSC) technique has been applied to investigate the solidification paths of a basaltic liquid. The starting glass was heated up to 1300◦C, kept at this superliquidus temperature for 2 h and cooled at rates (∆T/∆t) of 7, 60, 180, 1000, and 1800◦C/h, down to 800 and 600◦C. Glass transition temperature (Tg), crystallization temperature (Tx_HR) and melting temperature (Tm) were measured by in situ DSC spectra on heating. Tx measured along the cooling paths (Tx_CR) shows exothermic peaks that change from a single symmetric shape (7 and 60◦C/h) to multi-component patterns (180, 1000, and 1800◦C/h). The recovered products characterized by field emission gun source of the scanning electron microscopy and electron probe micro-analyzer-wavelength dispersive spectrometers show a phase assemblage of spinel (sp), clinopyroxene (cpx), melilite (mel), plagioclase (plg), and glass. Moreover, crystal size distributions (CSDs) and growth rates (Gmax and GCSD) were also determined. The crystal content slightly increases from 7 to 1800◦C/h. Faceted sp are present in all the run products with an amount always <2 area%. Cpx increases from 7 to 1800◦C/h, changing its texture from almost faceted to dendritic between 60 and 180◦C/h. The area% of mel follows an asymmetric Gaussian trend, while plg nucleates only at 7◦C/h with a content <2 area%. The coupling of DSC and SEM outcomes indicate that sp nucleate first, followed by cpx and mel (and/or plg). The increment of ∆T/∆t causes an increase of the CSD slope (m) and crystal population density per size (n0 ), as well as a decrease of the crystal size, for both cpx and sp. The log-linear CSD segments with different slopes at 7 and 60◦C/h suggest multiple nucleation events and crystal growth by coarsening. Gmax and GCSD for cpx and sp directly measured on the actual crystallization time by DSC spectra, both increase with the increasing of ∆T/∆t. The onset temperature of crystallization (Txi ) decreases as ∆T/∆t increases, following an exponential trend that defines the uppermost portion of a time-transformation-temperature-like curve. This analytical model allows us to quantitatively model the kinetic crystallization paths of dry basalts

Volume Flow Rate Estimation for Small Explosions at Mt. Etna, Italy, From Acoustic Waveform Inversion

Rapid assessment of the volume and the rate at which gas and pyroclasts are injected into the atmosphere during volcanic explosions is key to effective eruption hazard mitigation. Here, we use data from a dense infrasound network deployed in 2017 on Mt. Etna, Italy, to estimate eruptive volume flow rates (VFRs) during small gas-and-ash explosions.We use a finite-difference time-domain approximation to compute the acoustic Green's functions and perform a full waveform inversion for a multipole source, combining monopole and horizontal dipole terms. The inversion produces realistic estimates of VFR, on the order of 4 × 104 m3/s and well-defined patterns of source directivity. This is the first application of acoustic waveform inversion at Mt. Etna. Our results demonstrate that acoustic waveform inversion is a mature and robust tool for assessment of source parameters and holds potential as a tool to provide rapid estimates of VFR in near real time.This study was supported by NERC Grant NE/P00105X/1 and by European Unions Horizon 2020 Research and Innovation Programme Under the Marie Sklodowska-Curie Grant Agreement 798480

Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65-10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25-15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT

Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent of HER-2/neu Expression

Double transgenic mice overespressing the transforming rat HER-2/neu oncogene and the mutated p53, with both deminant-negative and a gain-of-function properties, display early aggressive and metastasizing parotid tumors. Multiple acinar and ductal hyperplasia foci overexpressing the HER-2/neu gene product are evident at wk 5 and progress to poorly differentiated carcinoma by wk 7. Mice die before wk 18 with invasive carcinomas and multiple metastases that no longer express HER-2/neu. A combination of repeated electroporations of plasmids coding for the extracellular and transmembrane domains of the rat HER-2/neu receptor with systemic IL-12 administrations started when the parotids that present diffuse hyperplasia protected all female and 50% of the male mice until the close of the experiment at wk 40. This combined treatment began when multifocal in situ - carcinomas that were already present cured 33% of the females and 25 % of the males. The most prominent immunologic features associated with the antitumor protection were the production of high titers of anti-HER-2/neu Abs and the nonappearance of cell-mediated cytotoxic reactivity. In conclusion, anti-HER-2/neu vaccination combined with systemic IL-12 control parotid carcinomas as far as p53 mutation makes their growth independent of HER-2/neu expression

Teacher confidence in professional training: The predictive roles of engagement and burnout

Teachers' work engagement positively impacts teachers' attitudes towards their job. Nevertheless, teachers may experience burnout during their career, which negatively impacts their professional learning opportunities. In this study we investigated the relationship between teachers' levels of burnout, work engagement, and their confidence in in-service training in a sample of Italian teachers. We expected that burnout mediated the relationship between work engagement and teachers' confidence in training. A total of 481 teachers completed self-report questionnaires about engagement and burnout, with an ad hoc Confidence in Training Index developed to assess their attitudes towards professional development courses. The mediation analysis confirmed that the teachers' levels of burnout mediated the relationship between their work engagement and their confidence in in-service training. Findings suggest that teacher confidence in policies about professional training should be evaluated by taking into account their level of engagement and burnout

LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice

Within 33 weeks of life, all 10 mammary glands of virgin BALB/c mice transgenic for the transforming rat HER-2/neu oncogene under the mammary tumor virus promoter (BALB-neuT mice) progress from atypical hyperplasia to invasive palpable carcinoma. Repeated DNA vaccination with plasmids coding for the extracellular and transmembrane domain of the protein product of rat HER-2/neu (r-p185neu) delayed tumor onset and reduced tumor multiplicity, but this protection eventually declined, and few mice were tumor free at 1 year of age. Association of plasmid vaccination with administration of soluble mouse LAG-3 (lymphocyte activation gene-3/CD223) generated by fusing the extracellular domain of murine LAG-3 to a murine IgG2a Fc portion (mLAG-3Ig) elicited a stronger and sustained protection that kept 70% of 1-year-old mice tumor free. Moreover, this combined vaccination, which was performed when multiple in situ carcinomas were already evident, extended disease-free survival and reduced carcinoma multiplicity. Inhibition of carcinogenesis was associated with markedly reduced epithelial cell proliferation and r-p185neu expression, whereas the few remaining hyperplastic foci were heavily infiltrated by reactive leukocytes. A stronger and enduring r-p185neu-specific cytotoxicity, a sustained release of IFN-γ and interleukin 4, and a marked expansion of both CD8+/CD11b+/CD28+ effector and CD8+/CD11b+/CD28- memory effector T-cell populations were induced in immunized mice. This combined vaccination also elicited a quicker and higher antibody response to r-p185neu, as well as an early antibody isotype switch. These data suggest that the appropriate costimulation provided by mLAG-3Ig enables DNA vaccination to establish an effective protection, probably by enhancing cross-presentation of the DNA coded antigen

Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis

We previously demonstrated that HER2/neu-driven mammary carcinogenesis can be prevented by an interleukin-12 (IL-12)-adjuvanted allogeneic HER2/neu-expressing cell vaccine. Since IL-12 can induce the release of interleukin-15 (IL-15), in the present study we investigated the role played by IL-15 in HER2/neu driven mammary carcinogenesis and in its immunoprevention

Electrochemotherapy of skin metastases from malignant melanoma: a PRISMA-compliant systematic review

The main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting. PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both for ECT alone and in combination with systemic treatments), local control (LC), and overall survival (OS) were collected. The methodological quality was assessed using a 20-item validated quality appraisal tool for case series. Overall, 18 studies were included in our analysis. In studies reporting “per patient” tumor response the pooled complete response (CR) was 35.7% (95%CI 26.0–46.0%), and the pooled ORR was 80.6% (95%CI 68.7–90.1%). Regarding “per lesion” response, the pooled CR was 53.5% (95%CI 42.1–64.7%) and the pooled ORR was 77.0% (95%CI 56.0–92.6%). One-year LC rate was 80%, and 1-year OS was 67–86.2%. Pain (24.2–92.0%) and erythema (16.6–42.0%) were the most frequent toxicities. Two studies reported 29.2% and 41.6% incidence of necrosis. ECT is effective in terms of tumor response and tolerated in patients with skin metastases from MM, albeit with a wide variability of reported results. Therefore, prospective trials in this setting are warranted

The FDM readout system for the TES bolometers of the SWIPE instrument on the balloon-borne LSPE experiment

We present the design and first tests of a prototype readout for the SWIPE instrument onboard the LSPE balloon-borne experiment. LSPE aims at measuring the linear polarization of the Cosmic Microwave Background (CMB) at large angular scales, to find the imprint of inflation on the B-mode CMB polarization. The SWIPE instrument hosts two focal planes hosting 163 TES Au/Mo spiderweb bolometers each, cooled at 0.3 K for the detection of microwave frequencies of 140, 220 and 240 GHz. To read all the detectors, a 16 channel frequency domain multiplexing readout system has been devised, consisting of LC resonators composed of custom Nb superconducting inductors and commercial SMD capacitors. A set-up consisting of 14 LC resonators shows that we can accommodate 16 channels in the frequency range between 200 kHz and 1.6 MHz, since the necessary line-widths can be achieved. A preliminary firmware for the generation and read-out of the biasing frequency comb is also discussed