Analysis of isoplanatic high resolution stellar fields by Starfinder code

We describe a new code for the deep analysis of stellar fields, designed for Adaptive Optics Nyquist-sampled images with high and low Strehl ratio. The Point Spread Function is extracted directly from the image frame, to take into account the actual structure of the instrumental response and the atmospheric effects. The code is written in IDL language and organized in the form of a self-contained widget-based application, provided with a series of tools for data visualization and analysis. A description of the method and some applications to AO data are presented.Comment: 10 pages, 13 figures. Accepted for publication in Astron.& Astrophys. Sup. Se

StarFinder: an IDL GUI based code to analyze crowded fields with isoplanatic correcting PSF fitting

StarFinder is a new code for the deep analysis of stellar fields, designed for well-sampled images with high and low Strehl ratio. It is organized in the form of a self-contained IDL widget-based application, with a 'user-friendly' graphic interface. We give here a general description of the code along with some applications to real data with space-invariant Point Spread Function (PSF). We present also some methods to handle anisoplanatic effects in wide-field Adaptive Optics (AO)observations.Comment: 9 pages, to to be published on "Proceeedings of Adaptive Optical Systems Technology",Proc.of SPIE,Vol.4007,2000. In pres

Clinical efficacy of minimally invasive surgical (MIS) and non-surgical (MINST) treatments of periodontal intra-bony defect. A systematic review and network meta-analysis of RCT's

Objective: The aim of this systematic review was to explore the efficacy of different minimal invasive surgical (MIS) and non-surgical (MINST) approaches for the treatment of intra-bony defect in terms of clinical attachment level (CAL) gain and periodontal pocket depth (PPD) reduction. / Methods: A detailed review protocol was designed according to PRISMA guideline. Online search was conducted on PubMed, Cochrane library and Embase. Only randomized clinical trials (RCTs) testing MIS or MINST procedure, with or without the application of a regenerative tool for the treatment of intra-bony defect, were included. Cochrane checklist for risk of bias assessment was used. Network meta-Analysis (NMAs) was used to rank the treatment efficacy. / Results: Nine RCTs accounting for 244 patients and a total of 244 defects were included. Only two studies were at low risk of bias. CAL gain for included treatment ranged from 2.58 ± 1.13 mm to 4.7 ± 2.5 mm while PPD reduction ranged from 3.19 ± 0.71 mm to 5.3 ± 1.5 mm. On the basis of the ranking curve, MINST showed the lowest probability to be the best treatment option for CAL gain. Pairwise comparisons and treatment rankings suggest superiority for regenerative approaches (CAL difference 0.78 mm, (0.14–1.41); P < 0.05) and surgical treatment elevating only the buccal or palatal flap (CAL difference: 0.95 mm, (0.33–1.57); P < 0.05). / Conclusions: Minimally invasive surgical (MIS) and non-surgical (MINST) periodontal therapy show promising results in the treatment of residual pocket with intra-bony defect. / Clinical relevance: MIS procedures represent a reliable treatment for isolated intra-bony defect

Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System

Background: Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 or its ligand (PD1/PDL1), elicit different immune-related adverse events (irAEs), but their global safety is incompletely characterized. Objective: The aim of this study was to characterize the spectrum, frequency, and clinical features of ICI-related adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS). Patients and methods: AEs from FAERS (up to June 2018) recording ICIs (ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab) as suspect were extracted. Comprehensive disproportionality analyses were performed through the reporting odds ratio (ROR) with 95% confidence interval (95% CI), using other oncological drugs as comparison. An overview of systematic reviews (OoSRs) was also undertaken to identify irAEs with consistent positive associations. Results: ICIs were recorded in 47,266 reports, submitted mainly by consumers receiving monotherapy with anti-PD1/PDL1 drugs. Three areas of toxicity emerged from both disproportionality analysis and the OoSRs (32 studies): endocrine (N = 2863; ROR = 6.91; 95% CI 6.60–7.23), hepatobiliary (2632; 1.33; 1.28–1.39), and respiratory disorders (7240; 1.04; 1.01–1.06). Different reporting patterns emerged for anti-CTLA4 drugs (e.g., hypophysitis, adrenal insufficiency, hypopituitarism, and prescribed overdose) and anti-PD1/PDL1 agents&nbsp;(e.g., pneumonitis, cholangitis, vanishing bile duct syndrome, tumor pseudoprogression, and inappropriate schedule of drug administration). No increased reporting emerged when comparing combination with monotherapy regimens, but multiple hepatobiliary/endocrine/respiratory irAEs were recorded. Conclusions: This parallel approach through contemporary post-marketing analysis and OoSRs confirmed that ICIs are associated with a multitude of irAEs, with different reporting patterns between anti-CTLA4 and anti-PD1/PDL1 medications. Close clinical monitoring is warranted to early diagnose and timely manage irAEs, especially respiratory, endocrine, and hepatic toxicities, which warrant further characterization; patient- and drug-related risk factors should be assessed through analytical pharmaco-epidemiological studies and prospective multicenter registries

The therapeutic effect of MIR-125b is enhanced by the prostaglandin endoperoxide synthase 2/cyclooxygenase 2 blockade and hampers ETS1 in the context of the microenvironment of bone metastasis

Bone is the most common site for breast cancer spread. In the pro-metastatic cell line 1833, derived from MDA-MB-231 breast adenocarcinoma cells, both hypoxia and hepatocyte growth factor (HGF) influence the effect of miR-125b on ETS proto-oncogene 1 transcription factor (ETS1). The effect of hypoxia inducible factor 1 alpha subunit (HIF1A), known to promote metastatic spread by upregulating prostaglandin endoperoxide synthase 2 (PTGS2), may be dampened by miR-125b targeting PTGS2. Here, we investigated whether miR-125b plays a role in breast cancer metastasis by measuring its activity in response to the chemotherapeutic agent NS-398 in a xenograft model. NS-398 is typically used in the clinic to target PTGS2. We also aimed to describe the molecular mechanisms in vitro, since the enhancement of epithelial properties may favor the efficacy of therapies. We report that in the xenograft model, miR-125b reduced metastasis to the bone. We also report suppression of PTGS2 enhanced survival by decreasing HIF1A in cells within the bone marrow. In 1833 cells transfected with a miR-125b mimic we observed several phenotypic changes including enhancement of the epithelial marker E-cadherin, a reduction of mesenchymal-associated genes and a reduction of WNT-associated stem cell signaling. Our findings suggest that in vivo, key players of the bone microenvironment promoting breast cancer spread are regulated by miR-125b. In future, biological molecules imitating miR-125b may enhance the sensitivity of chemotherapeutic agents used to counteract bone metastases

Functions and epigenetic regulation of Wwox in bone metastasis from breast carcinoma : Comparison with primary tumors

Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1\u3b1 (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma. In hypoxic-bone metastatic cells, Wwox enhances HIF-1\u3b1 stabilization, phosphorylation, and nuclear translocation. Consistently, in bone-metastasis specimens Wwox localizes in cytosolic/perinuclear area, while TAZ (transcriptional co-activator with PDZ-binding motif) and HIF-1\u3b1 co-localize in nuclei, playing specific regulatory mechanisms: TAZ is a co-factor of HIF-1, and Wwox regulates HIF-1 activity by controlling HIF-1\u3b1. In vitro, DNA methylation affects Wwox-protein synthesis; hypoxia decreases Wwox-protein level; hepatocyte growth factor (HGF) phosphorylates Wwox driving its nuclear shuttle, and counteracting a Twist program important for the epithelial phenotype and metastasis colonization. In agreement, in 1833-xenograft mice under DNA-methyltransferase blockade with decitabine, Wwox increases in nuclei/cytosol counteracting bone metastasis with prolongation of the survival. However, Wwox seems relevant for the autophagic process which sustains metastasis, enhancing more Beclin-1 than p62 protein levels, and p62 accumulates under decitabine consistent with adaptability of metastasis to therapy. In conclusion, Wwox methylation as a bone-metastasis therapeutic target would depend on autophagy conditions, and epigenetic mechanisms regulating Wwox may influence the phenotype of bone metastasis

Cell and signal components of the microenvironment of bone metastasis are affected by hypoxia

Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients

On the Size Difference between Red and Blue Globular Clusters

Several recent studies have reported a mean size difference of about 20% between the metal-rich and metal-poor subpopulations of globular clusters (GCs) in a variety of galaxies. In this paper we investigate the possibility that the size difference might be a projection effect, resulting from a correlation between cluster size and galactocentric distance, combined with different radial distributions of the GC subpopulations. We find that projection effects may indeed account for a size difference similar to the observed one, provided that there is a steep relation between GC size and galactocentric distance in the central parts of the GC system and that the density of GCs flattens off near the center in a manner similar to a King profile. For more centrally peaked distributions, such as a de Vaucouleurs law, or for shallower size-radius relations, projection effects are unable to produce the observed differences in the size distributions.Comment: 30 pages, including 14 figures and 2 tables. Accepted for publication in Ap

Vitamin d and the risk of non-melanoma skin cancer: A systematic literature review and meta-analysis on behalf of the italian melanoma intergroup

We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation