Enhancing the significance of gravitational wave bursts through signal classification

The quest to observe gravitational waves challenges our ability to discriminate signals from detector noise. This issue is especially relevant for transient gravitational waves searches with a robust eyes wide open approach, the so called all- sky burst searches. Here we show how signal classification methods inspired by broad astrophysical characteristics can be implemented in all-sky burst searches preserving their generality. In our case study, we apply a multivariate analyses based on artificial neural networks to classify waves emitted in compact binary coalescences. We enhance by orders of magnitude the significance of signals belonging to this broad astrophysical class against the noise background. Alternatively, at a given level of mis-classification of noise events, we can detect about 1/4 more of the total signal population. We also show that a more general strategy of signal classification can actually be performed, by testing the ability of artificial neural networks in discriminating different signal classes. The possible impact on future observations by the LIGO-Virgo network of detectors is discussed by analysing recoloured noise from previous LIGO-Virgo data with coherent WaveBurst, one of the flagship pipelines dedicated to all-sky searches for transient gravitational waves

Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: a dose-response study

AbstractWhen testing the response to β2-agonist drugs in severe chronic obstructive pulmonary disease (COPD), a dose-response assessment should be undertaken. This study compares the time course of inhaled salmeterol (25, 50 and 75 μg) and formoterol (12, 24 and 36 μg) at different doses in a group of 12 patients with partially reversible, but severe COPD (FEV1 of 12–32% of predicted values after β2-agonist drugs had been withheld for 24 h). All doses of salmeterol and formoterol induced a significant (P<0·01) spirometric improvement over the 12-h monitoring period, when compared to the spirometric improvement after placebo, but while formoterol induced a dose-dependent increase of the FVC, FEV1 and FEF50, this was not the case for salmeterol. In fact, 75 μg salmeterol did not produce a further improvement of these parameters. Mean peak bronchodilation, expressed as the increase in FEV1 over baseline values, occurred 2 h after inhalation of the three doses of salmeterol, and 1 h after inhalation of the three doses of formoterol. A comparison of 50 μg salmeterol with 12 μg or 24 μg formoterol (clinically recommended doses), showed that improvement of FEV1 after salmeterol was statistically (P<0·05) higher than that after the two doses of formoterol, although the mean peak bronchodilations were similar. This was because salmeterol has a longer duration of action than formoterol. These data demonstrate that salmeterol is equally effective as, but longer-acting than, formoterol at clinically recommended doses in patients suffering from COPD, with severe airway obstruction. Moreover, these data suggest that 50 μg is the best dosage for salmeterol in these patients

Exploring the role of fallopian ciliated cells in the pathogenesis of high-grade serous ovarian cancer

High-grade serous epithelial ovarian cancer (HGSOC) is the fifth leading cause of cancer death in women and the first among gynecological malignancies. Despite an initial response to standard chemotherapy, most HGSOC patients relapse. To improve treatment options, we must continue investigating tumor biology. Tumor characteristics (e.g., risk factors and epidemiology) are valuable clues to accomplish this task. The two most frequent risk factors for HGSOC are the lifetime number of ovulations, which is associated with increased oxidative stress in the pelvic area caused by ovulation fluid, and a positive family history due to genetic factors. In the attempt to identify novel genetic factors (i.e., genes) associated with HGSOC, we observed that several genes in linkage with HGSOC are expressed in the ciliated cells of the fallopian tube. This finding made us hypothesize that ciliated cells, despite not being the cell of origin for HGSOC, may take part in HGSOC tumor initiation. Specifically, malfunction of the ciliary beat impairs the laminar fluid flow above the fallopian tube epithelia, thus likely reducing the clearance of oxidative stress caused by follicular fluid. Herein, we review the up-to-date findings dealing with HGSOC predisposition with the hypothesis that fallopian ciliated cells take part in HGSOC onset. Finally, we review the up-to-date literature concerning genes that are located in genomic loci associated with epithelial ovarian cancer (EOC) predisposition that are expressed by the fallopian ciliated cells

Relating seismic velocities, thermal cracking and permeability in Mt. Etna and Iceland basalts

We report simultaneous laboratory measurements of seismic velocities and fluid permeability on lava flow basalt from Etna (Italy) and columnar basalt from Seljadur (Iceland). Measurements were made in a servo-controlled steady-state-flow permeameter at effective pressures from 5–80 MPa, during both increasing and decreasing pressure cycles. Selected samples were thermally stressed at temperatures up to 900 °C to induce thermal crack damage. Acoustic emission output was recorded throughout each thermal stressing experiment. At low pressure (0–10 MPa), the P-wave velocity of the columnar Seljadur basalt was 5.4 km/s, while for the Etnean lava flow basalt it was only 3.0–3.5 km/s. On increasing the pressure to 80 MPa, the velocity of Etnean basalt increased by 45%–60%, whereas that of Seljadur basalt increased by less than 2%. Furthermore, the velocity of Seljadur basalt thermally stressed to 900 °C fell by about 2.0 km/s, whereas the decrease for Etnean basalt was negligible. A similar pattern was observed in the permeability data. Permeability of Etnean basalt fell from about 7.5×10−16 m2 to about 1.5×10−16 m2 over the pressure range 5–80 MPa, while that for Seljadur basalt varied little from its initial low value of 9×10−21 m2. Again, thermal stressing significantly increased the permeability of Seljadur basalt, whilst having a negligible effect on the Etnean basalt. These results clearly indicate that the Etnean basalt contains a much higher level of crack damage than the Seljadur basalt, and hence can explain the low velocities (3–4 km/s) generally inferred from seismic tomography for the Mt. Etna volcanic edifice

Immunopositivity for Histone MacroH2A1 Isoforms Marks Steatosis-Associated Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously

Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation

Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4+/CD25+/FoxP3+ T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance

miR-16-5p, miR-103-3p, and miR-27b-3p as Early Peripheral Biomarkers of Fetal Growth Restriction

Current tests available to diagnose fetal hypoxia in-utero lack sensitivity thus failing to identify many fetuses at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as non-invasive biomarkers for pregnancy complications. With the intent to identify putative markers of fetal growth restriction (FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a group of microRNAs, known to be regulated by hypoxia. The expression of microRNAs was evaluated in maternal plasma samples collected from (1) women carrying a preterm FGR fetus (FGR group) or (2) women with an appropriately grown fetus matched at the same gestational age (Control group). To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery. Four microRNAs were identified as possible candidates for the diagnosis of FGR: miR-16-5p, miR-103-3p, miR-107-3p, and miR-27b-3p. All four selected miRNAs, measured by RT-PCR, resulted upregulated in FGR blood samples before the 32nd week of gestation. By contrast, miRNA103-3p and miRNA107-3p, analyzed between the 32nd and 37th week of gestation, showed lower expression in the FGR group compared to aged matched controls. Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic interventions to alleviate the burden of this disease

miR-16-5p, miR-103-3p, and miR-27b-3p as Early Peripheral Biomarkers of Fetal Growth Restriction

none9noCurrent tests available to diagnose fetal hypoxia in-utero lack sensitivity thus failing to identify many fetuses at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as non-invasive biomarkers for pregnancy complications. With the intent to identify putative markers of fetal growth restriction (FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a group of microRNAs, known to be regulated by hypoxia. The expression of microRNAs was evaluated in maternal plasma samples collected from (1) women carrying a preterm FGR fetus (FGR group) or (2) women with an appropriately grown fetus matched at the same gestational age (Control group). To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery. Four microRNAs were identified as possible candidates for the diagnosis of FGR: miR-16-5p, miR-103-3p, miR-107-3p, and miR-27b-3p. All four selected miRNAs, measured by RT-PCR, resulted upregulated in FGR blood samples before the 32nd week of gestation. By contrast, miRNA103-3p and miRNA107-3p, analyzed between the 32nd and 37th week of gestation, showed lower expression in the FGR group compared to aged matched controls. Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic interventions to alleviate the burden of this disease.openTagliaferri S.; Cepparulo P.; Vinciguerra A.; Campanile M.; Esposito G.; Maruotti G.M.; Zullo F.; Annunziato L.; Pignataro G.Tagliaferri, S.; Cepparulo, P.; Vinciguerra, A.; Campanile, M.; Esposito, G.; Maruotti, G. M.; Zullo, F.; Annunziato, L.; Pignataro, G

Predictive role of the p16 immunostaining pattern in atypical cervical biopsies with less common high risk hpv genotypes

P16 immunostaining is considered a useful surrogate of transcriptionally active high‐risk (hr) HPV infection. Only strong and widespread “block‐like” immunoreactivity is considered specific, whereas weak/focal p16 positive immunostaining is considered not specific, and follow‐up and HPV molecular detection is not indicated. The aim of the study was to evaluate the presence of HPV DNA and Ki67 immunostaining in 40 cervical atypical biopsies (CALs) with mild and focal histological features suggestive of HPV infection—20 cases with weak/focal p16 positive immunoreactivity and 20 cases negative for p16 expression. In 16/20 weak/focal p16 positive CALs (80%), the INNO‐LiPA HPV genotyping detected hrHPV genotypes (HPV 31, 51, 56, 59, 26, 53, 66, 73, and 82). Co‐infection of two or more hrHPV genotypes was often evidenced. HPV16 and 18 genotypes were never detected. Ki67 immunostaining was increased in 10/20 cases (50%). In 19/20 p16 negative CALs, hrHPV infection was absent and Ki67 was not increased. These results suggest that weak/focal p16 immunostaining represents the early stage of transcriptionally active infection, strongly related to the presence of less common hrHPV genotypes, probably with a slower transforming power, but with a potential risk of progression if the infection persists. HPV DNA genotyping and follow‐up could be useful in these cases to verify if they are able to evolve into overt dysplastic changes and to improve knowledge of less common hrHPV genotypes