A First Comparison Between LIGO and Virgo Inspiral Search Pipelines

This article reports on a project that is the first step the LIGO Scientific Collaboration and the Virgo Collaboration have taken to prepare for the mutual search for inspiral signals. The project involved comparing the analysis pipelines of the two collaborations on data sets prepared by both sides, containing simulated noise and injected events. The ability of the pipelines to detect the injected events was checked, and a first comparison of how the parameters of the events were recovered has been completed.Comment: GWDAW-9 proceeding

External gap progression after cyclic fatigue of adhesive overlays and crowns made with high translucency zirconia or lithium silicate

Objectives: To evaluate three-dimensional external gap progression after chewing simulation of high translucency zirconia (HTZ) and zirconia-reinforced lithium silicate (ZLS) applied on endodontically treated teeth with different preparation designs. Materials and Method: Endodontically treated molars were prepared with low-retentive (adhesive overlay) and high-retentive (full crown) designs above cementum-enamel junction and restored with HTZ and ZLS. Micro-computed tomography analysis was assessed before and after chewing simulation to evaluate three-dimensionally the external gap progression. Results were statistically analyzed with two-way ANOVA and post-hoc Tukey test. Results: High-retentive preparation design had a significantly inferior gap progression compared to the overlay preparation (p < 0.01); ZLS exhibited a significant inferior gap progression compared to HTZ (p < 0.01). Conclusions: High-retentive preparations restored with ZLS seem to better perform in maintaining the sealing of the external margin after cyclic fatigue. Clinical significance: The clinician should pay attention to the proper combination of preparation designs and ceramic material selection for an endodontically treated molar restoration. HTZ seems to perform worse than lithium silicate in terms of marginal sealing, still showing lacks in resistance to cyclic fatigue when adhesive preparations are performed

Izdvajanje bakterije Escherichia coli O157:H7 i njezin dokaz lančanom reakcijom polimerazom u crijevima filipinskih šišmiša.

It is currently reported that bats in the Philippines harbor bacterial organism (Salmonella spp.) with pathogenic potential. The paper describes the conventional isolation and polymerase chain reaction (PCR) assay for the detection of another bacterium, Escherichia coli, from a sample population of 56 apparently healthy bats collected from Laguna and Quezon City, Philippines. Nineteen of the samples were positive for E. coli using the conventional method of isolation, while PCR molecularly detected the bacteria in 15 samples. The presence of hemolysin among the isolates was not observed. The isolates were subjected to E. coli O157:H7 serotype detection using the latex agglutination test and another PCR assay specific for this serotype. The data revealed that none of the isolates was positive for E. coli O157:H7 using serological and molecular diagnostic methods, which indicates that bats from Laguna and Quezon City, Philippines were not carriers of the pathogenic strain, E. coli O157:H7. The study also presents the first local report of conventional isolation and molecular detection of E. coli from Philippine bats.Poznato je da šišmiši na Filipinima mogu biti nositelji potencijalno patogenih bakterija, npr. salmonela. U radu je opisano izdvajanje i dokaz lančanom reakcijom polimerazom bakterije Escherichia coli iz 56 naizgled zdravih šišmiša uhvaćenih na području Laguna i Quezon City na Filipinima. E. coli bila je izdvojena iz 19 uzoraka, dok je lančanom reakcijom polimerazom ona bila dokazana u 15 uzoraka. Izolati nisu tvorili hemolizu, a lateks aglutinacija i specifični PCR rabljeni su za dokaz serovara O157:H7 bakterije E. coli. Nijedan izolat nije pripadao serovaru O157:H7, na osnovi čega se može zaključiti da šišmiši na području Laguna i Quezon City na Filipinima nisu nositelji patogenog soja E. coli O157:H7. Istraživanje je ujedno prvi dokaz o izdvajanju i molekularnoj identifikaciji bakterije E. coli u šišmiša na Filipinima

Analyses of 123 Peripheral Human Immune Cell Subsets: Defining Differences with Age and between Healthy Donors and Cancer Patients not Detected in Analysis of Standard Immune Cell Types

Recent advances in human immunology have led to the identification of novel immune cell subsets and the biological function of many of these subsets has now been identified. The recent US Food and Drug Administration approval of several immunotherapeutics for the treatment of a variety of cancer types and the results of ongoing immunotherapy clinical studies requires a more thorough interrogation of the immune system. We report here the use of flow cytometry-based analyses to identify 123 immune cell subsets of peripheral blood mononuclear cells. The use of these panels defines multiple differences in younger (< 40 years) vs. older (≥ 40 years) individuals and between aged-matched apparently healthy individuals and metastatic cancer patients, aspects not seen in the analysis of the following standard immune cell types: CD8, CD4, natural killer, natural killer-T, regulatory T, myeloid derived suppressor cells, conventional dendritic cells (DCs), plasmacytoid DCs and B cells. The use of these panels identifying 123 immune cell subsets may aid in the identification of patients who may benefit from immunotherapy, either prior to therapy or early in the immunotherapeutic regimen, for the treatment of cancer or other chronic or infectious diseases

Samarium-153-EDTMP (Quadramet®) With or Without Vaccine in Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase 2 Trial

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. Forty-four patients enrolled. Eighteen and 21 patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and combination arms, respectively. There was no statistical difference in the primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP alone and combination arms, respectively, having stable disease at approximately the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046). No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA) decline \u3e 30% compared with four patients (of 21) in the combination arm, including three with PSA decline \u3e 50%. Toxicities were similar between arms and related to number of Sm-153-EDTMP doses administered. These results provide the rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in combination with PSA-TRICOM

Peroral Amphotericin B Polymer Nanoparticles Lead to Comparable or Superior In Vivo Antifungal Activity to That of Intravenous Ambisome® or Fungizone™

Background: Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70–90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical. Methodology: Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113±20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery. Conclusions: The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™and responds only modestly to AmBisome®

Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ~280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics

A randomised control crossover trial of a theory based intervention to improve sun-safe and healthy behaviours in construction workers:Study protocol

Abstract Background Exposure to sunlight can have both positive and negative health impacts. Excessive exposure to ultra-violet (UV) radiation from the sun can cause skin cancer, however insufficient exposure to sunlight has a detrimental effect on production of Vitamin D. In the construction industry there are onsite proactive behaviours for safety, but sun-safety remains a low priority. There is limited research on understanding the barriers to adopting sun-safe behaviours and the association this may have with Vitamin D production. This paper reports a protocol for an intervention study, using text messaging in combination with a supportive smartphone App. The intervention aims to both reduce UV exposure during months with higher UV levels and promote appropriate dietary changes to boost Vitamin D levels during months with low UV levels. Method/design Approximately 60 construction workers will be recruited across the United Kingdom. A randomised control crossover trial (RCCT) will be used to test the intervention, with randomisation at site level – i.e. participants will receive both the control (no text messages or supportive App support) and intervention (daily text messages and supportive App). Using the Theory of Planned Behaviour (TPB) the intervention focuses on supporting sun-safety and healthy dietary decisions in relation to Vitamin D intake. The intervention emphasises cultivating the perception of normative support in the workplace, increasing awareness of control and self-efficacy in taking sun-protective behaviours, making healthier eating choices to boost Vitamin D, and tackling stigmas attached to image and group norms. Each study epoch will last 21 days with intervention text messages delivered on workdays only. The supportive App will provide supplementary information about sun protective behaviours and healthy dietary choices. The primary outcome measure is 25-hydroxy-Vitamin D [25(OH)D] level (obtained using blood spot sampling), which will be taken pre and post control and intervention periods. Secondary outcome measures are two-fold, (1) using the TPB to detect changes in behaviour, and (2) quantifying UV exposure during the UK peak radiation season (April–September) using body-mounted UV sensors. Discussion This study will provide important information about the effectiveness of a technology-based intervention to promote sun-safety and healthy behaviours in outdoor construction workers. Trial registration ISRCTN15888934 retrospectively registered 15.01.2018