A schlieren method for ultra-low angle light scattering measurements

We describe a self calibrating optical technique that allows to perform absolute measurements of scattering cross sections for the light scattered at extremely small angles. Very good performances are obtained by using a very simple optical layout similar to that used for the schlieren method, a technique traditionally used for mapping local refraction index changes. The scattered intensity distribution is recovered by a statistical analysis of the random interference of the light scattered in a half-plane of the scattering wave vectors and the main transmitted beam. High quality data can be obtained by proper statistical accumulation of scattered intensity frames, and the static stray light contributions can be eliminated rigorously. The potentialities of the method are tested in a scattering experiment from non equilibrium fluctuations during a free diffusion experiment. Contributions of light scattered from length scales as long as Lambda=1 mm can be accurately determined.Comment: 7 pages, 3 figure

Guiding of KeV Ions between Two Insulating Parallel Plates

Experimental data are presented for low-energy singly charged ion transport between two insulating parallel plates. Using a beam intensity of approximately 20 pA, measurements of the incoming and transmitted beams provide quantitative temporal information about the charge deposited on the plates and the guiding probability. Using a smaller beam intensity (~ 1 pA) plate charging and discharging properties were studied as a function of time. These data imply that both the charge deposition and decay along the surface and through the bulk need to be modeled as acting independently. A further reduction of beam intensity to ~ 25 fA allowed temporal imaging studies of the positions and intensities of the guided beam plus two bypass beams to be performed. SIMION software was used to simulate trajectories of the guided and bypass beams, to provide information about the amount and location of deposited charge and, as a function of charge patch voltage, the probability of beam guiding and how much the bypass beams are deflected plus to provide information about the electric fields. An equivalent electric circuit model of the parallel plates, used to associate the deposited charge with the patch voltage implies that the deposited charge is distributed primarily on the inner surface of the plates, transverse to the beam direction, rather than being distributed throughout the entire plate

MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia

OBJECTIVE: To evaluate the expression of microRNA (miR)-551b in patients with low and high grade cervical intraepithelial neoplasia (CIN) and to find an association with high-risk Human Papillomavirus (HR-HPV) infection-related prognostic biomarkers. PATIENTS AND METHODS: The expression level of miR-551b was determined in 50 paraffin-embedded cervical specimens (10 normal squamous epithelium, 18 condylomas, 8 CIN1, and 14 CIN2-3) using quantitative Real-time polymerase chain reaction (qRT-PCR). χ2-test compared miR-551b expression in different diagnosis groups. An Ordered Logistic Regression and a Probit correlation were made to correlate miR-551b expression levels with the cervical tissue histological findings. The immunohistochemical distribution of p16 and Ki-67 according to histopathological findings was also assessed. RESULTS: The distribution of the miR-551b expression profile was significantly lower in CIN1-3 samples compared to other histological diagnosis groups (condyloma and negative). The expression levels were inversely correlated to the cervical pathological grade, from negative to CIN2-3. A 1% increase in miR-551b expression level produced an increase of 19% to the probability of a minor histological grade diagnosis in a range from negative to CIN2-3 and an increase of 13% to the probability of a negative histological grade diagnosis. Among the cases with miR-551b expression < 0.02 (considered as cut-off value) a significant statistical correlation was found between p16 and Ki-67 expression and the diagnosis of CIN2-3. CONCLUSIONS: O ur d ata s howed a s ignificant inverse correlation between miR-551b expression and the histological grading of the lesions, suggesting a tumor suppressive function in the different stages of cervical dysplasia

Natural Formulations Based on Olea europaea L. Fruit Extract for the Topical Treatment of HSV-1 Infections

In the present study, a hydroxytyrosol-rich Olea europaea L. fruit extract (OFE) was added to three thoroughly green formulations—hydrogel, oleogel, and cream—in order to evaluate their antiviral activity against HSV-1. The extract was characterized by different analytical techniques, i.e., FT-IR, XPS, and TGA. HPLC analyses were carried out to monitor the content and release of hydroxytyrosol in the prepared formulations. The total polyphenol content and antioxidant activity were investigated through Folin–Ciocâlteu’s reagent, DPPH, and ABTS assays. The ability of the three formulations to convey active principles to the skin was evaluated using a Franz cell, showing that the number of permeated polyphenols in the hydrogel (272.1 ± 1.8 GAE/g) was significantly higher than those in the oleogel and cream (174 ± 10 and 179.6 ± 2 GAE/g, respectively), even if a negligible amount of hydroxytyrosol crossed the membrane for all the formulations. The cell viability assay indicated that the OFE and the three formulations were not toxic to cultured Vero cells. The antiviral activity tests highlighted that the OFE had a strong inhibitory effect against HSV-1 with a 50% inhibitory concentration (IC50) at 25 µg/mL, interfering directly with the viral particles. Among the three formulations, the hydrogel exhibited the highest antiviral activity also against the acyclovir-resistant strain

Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab

Impact on visual acuity in neovascular age related macular degeneration (Namd) in europe due to covid-19 pandemic lockdown

This is a retrospective, multicenter study of consecutive patients with nAMD scheduled for a visit and/or a treatment with an intravitreal injection (IVI) during the 3 months before lockdown in the Ophthalmology Departments of six centers of Europe.The study was conducted on 546 patients, of which 55.13% were females, almost 100% of the patients were White/Caucasian race, and 71.53% of the patients presented a type 1 macular neovascularization (NVM). A total of 62.82% of patients (343 patients) that were on scheduled clinic visits and/or intravitreal injection treatment during the 3 months before the quarantine did not attend either to visit or for treatment during the lockdown. The mean number of injections during the lockdown was significantly reduced. This was followed by a significant reduction in the mean best-corrected visual acuity (BCVA) between the 3 months before the lockdown (mean BCVA of 60.68 ± 19.77 letters) and 6 months after lockdown (mean BCVA of 56.98 ± 22.59 letters). Patients with better BCVA before the lockdown and the ones showing neovascular activity were more likely to attend their scheduled visits and/or IVI treatments. The COVID-19 pandemic and the lockdown have led to a decrease in the number of IVI treatments in patients with nAMD, evidencing a significant vision loss at 6 months

Splicing Factors Induce Cystic Fibrosis Transmembrane Regulator Exon 9 Skipping through a Nonevolutionary Conserved Intronic Element

In monosymptomatic forms of cystic fibrosis such as congenital bilateral absence of vas deferens, variations in the TG(m) and T(n) polymorphic repeats at the 3' end of intron 8 of the cystic fibrosis transmembrane regulator (CFTR) gene are associated with the alternative splicing of exon 9, which results in a nonfunctional CFTR protein. Using a minigene model system, we have previously shown a direct relationship between the TG(m)T(n) polymorphism and exon 9 splicing. We have now evaluated the role of splicing factors in the regulation of the alternative splicing of this exon. Serine-arginine-rich proteins and the heterogeneous nuclear ribonucleoprotein A1 induced exon skipping in the human gene but not in its mouse counterpart. The effect of these proteins on exon 9 exclusion was strictly dependent on the composition of the TG(m) and T(n) polymorphic repeats. The comparative and functional analysis of the human and mouse CFTR genes showed that a region of about 150 nucleotides, present only in the human intron 9, mediates the exon 9 splicing inhibition in association with exonic regulatory elements. This region, defined as the CFTR exon 9 intronic splicing silencer, is a target for serine-arginine-rich protein interactions. Thus, the nonevolutionary conserved CFTR exon 9 alternative splicing is modulated by the TG(m) and T(n) polymorphism at the 3' splice region, enhancer and silencer exonic elements, and the intronic splicing silencer in the proximal 5' intronic region. Tissue levels and individual variability of splicing factors would determine the penetrance of the TG(m)T(n) locus in monosymptomatic forms of cystic fibrosis

Trace elements and isotopes analyses on historical samples of white sharks from the Mediterranean Sea

The white shark Carcharodon carcharias has been present in the Mediterranean Sea since 3.2 million years ago. Nevertheless, the current population shows a low genetic variability suggesting an endangered small population, on which there is scarce information regarding ecotoxicology or trophic ecology. Given that white shark's sightings are rare in the Mediterranean and the possibility of obtaining samples is highly limited, the aim of this research was to provide general information regarding the concentration of trace elements and stable isotopes (delta N-15 and delta C-13). Laboratory analyses were performed on 18 and 12 subsamples from two different white sharks' vertebrae obtained from two adult specimens caught in 1987, in Favignana Island, Italy. Perforations were made along the vertebrae to describe both trace elements and stable isotopes at different life stages. A total of 38 trace elements were analysed, in which the highest concentrations were found in Fe, Sr, U, Pb, and Zn. The fluctuations of these elements during the ontogeny of both individuals could have been related to changes in diet and environment, although the specific origin remains unknown. Regarding stable isotopes, the vertebrae from the male showed an isotopic range from 9.6 parts per thousand to 10.8 parts per thousand (delta N-15) and from -16.5 parts per thousand to -13.0 parts per thousand (delta C-13) with a mean +/- SD value of 10.3 +/- 0.4 parts per thousand for delta N-15 and -14.6 +/- 1.3 parts per thousand for delta C-13; whereas the female vertebrae had an isotopic range from 9.8 parts per thousand to 11.1 parts per thousand (delta N-15) and from -16.9 parts per thousand to -15.0 parts per thousand (delta C-13), with a mean +/- SD value of 10.8 +/- 0.6 parts per thousand for delta N-15 and -15.8 +/- 0.8 parts per thousand for delta C-13. There were no significant delta N-15 differences (U = 6, p = 0.07346) between the two individuals. However, there were just significant differences in delta C-13 (t = -1.8, p = 0.049256), which could suggest sexual segregation in terms of habitat use and feeding habits

Differential diagnosis between Marfan syndrome and Loeys–Dietz syndrome type 4: A novel chromosomal deletion covering tgfb2

Marfan syndrome (MFS) and Loeys–Dietz syndrome type 4 (LDS4) are two hereditary connective tissue disorders. MFS displays ectopia lentis as a distinguishing, characterising feature, and thoracic aortic ectasia, aneurysm, dissection, and systemic features as manifestations overlapping with LDS4. LDS4 is characterised by the presence of hypertelorism, cleft palate and/or bifid uvula, with possible ectasia or aneurysms in other arteries. The variable age of onset of clinical manifestations makes clinical diagnosis more difficult. In this study, we report the case of a patient with Marfan syndrome diagnosed at our centre at the age of 33 on the basis of typical clinical manifestations of this syndrome. At the age of 38, the appearance of ectasia of the left common iliac artery and tortuosity of the iliac arteries suggested the presence of LDS4. Next Generation Sequencing (NGS) analysis, followed by Array-CGH, allowed the detection of a novel chromosomal deletion including the entire TGFB2 gene, confirming not only the clinical suspicion of LDS4, but also the clinical phenotype associated with the haploinsufficiency mechanism, which is, in turn, associated with the deletion of the entire gene. The same mutation was detected in the two young sons. This emblematic case confirms that we must be very careful in the differential diagnosis of these two pathologies, especially before the age of 40, and that, in young subjects suspected to be affected by MFS in particular, we must verify the diagnosis, extending genetic analysis, when necessary, to the search for chromosomal alterations. Recently, ectopia lentis has been reported in a patient with LDS4, confirming the tight overlap between the two syndromes. An accurate revision of the clinical parameters both characterising and overlapping the two pathologies is highly desirable

New procedures for testing whether stock price processes are martingales

We propose procedures for testing whether stock price processes are martingales based on limit order type betting strategies. We first show that the null hypothesis of martingale property of a stock price process can be tested based on the capital process of a betting strategy. In particular with high frequency Markov type strategies we find that martingale null hypotheses are rejected for many stock price processes