Massive stars in the hinterland of the young cluster, Westerlund 2

Accepted for publication in MNRAS, 13 July 2018. 16 pages, plus one-page table in an appendix.An unsettled question concerning the formation and distribution of massive stars is whether they must be born in massive clusters and, if found in less dense environments, whether they must have migrated there. With the advent of wide-area digital photometric surveys, it is now possible to identify massive stars away from prominent Galactic clusters without bias. In this study we consider 40 candidate OB stars found in the field around the young massive cluster, Westerlund 2, by Mohr-Smith et al.: these are located inside a box of 1.5 × 1.5 deg 2 and are selected on the basis of their extinctions and K magnitudes.We present VLT/X-shooter spectra of two of the hottest O stars, respectively 11 and 22 arcmin from the centre of Westerlund 2. They are confirmed as O4V stars, with stellar masses likely to be in excess of 40 M ·. Their radial velocities relative to the non-binary reference object, MSP 182, in Westerlund 2 are -29.4 ± 1.7 and -14.4 ± 2.2 km s -1, respectively. Using Gaia DR2 proper motions we find that between 8 and 11 early O/WR stars in the studied region (including the two VLT targets, plus WR 20c and WR 20aa) could have been ejected fromWesterlund 2 in the last one million years. This represents an efficiency of massive-star ejection of up to ~ 25 per cent. On sky, the positions of these stars and their proper motions show a near N-S alignment. We discuss the possibility that these results are a consequence of prior sub-cluster merging combining with dynamical ejection.Peer reviewe

Efficacy and Safety of Ciltacabtagene Autoleucel and Idecabtagene Vicleucel in Multiple Myeloma Patients

Background: Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are chimeric antigen receptor (CAR) T-cell therapies used to treat adult patients with relapsed or refractory multiple myeloma (rrMM) after at least four lines of therapy. However, no head-to-head clinical trials to compare them have been conducted. Objective: To compare between CARTITUDE-1 and KarMMa clinical trials in terms of efficacy, safety, and patient characteristics. Method: Overall response rate (ORR) and safety signals were compared using reporting odds ratios (RORs) with 95% confidence intervals (CIs) at p \u3c 0.05. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan–Meier method with a log-rank test. Patient characteristics were compared using the chi-square test. Statistical analyses were conducted using Microsoft Excel and R version 4.0.5. Results: Statistically significant differences were observed between cilta-cel and ide-cel in terms of ORR, complete response (CR), OS, and PFS (p \u3c 0.05). Partial response (PR) showed no statistically significant difference (p \u3e 0.05). Ide-cel was significantly associated with higher incidences of any Grade ≥ 3 adverse events than cilta-cel. Cilta-cel on the other hand, was significantly associated with higher incidences of leukopenia, lymphopenia, and CRS Grade 1 & 2 than ide-cel (RORs \u3e 1, p \u3c 0.05). Penta-drug refractory showed a statistically significant difference between cilta-cel and ide-cel clinical trials. Conclusion: This study found that cilta-cel is a superior treatment over ide-cel with better efficacy and less incidence of serious adverse events

The Landscape of Cellular and Gene Therapy Products: Cost, Approvals, and Discontinuations

Background The past 10 years witnessed a significant increase in the approval of cellular and gene therapy products worldwide. The US Food and Drug Administration (FDA) approved 3 gene therapy products within the last 4 months of 2017. The objective of this study was to examine the approval characteristics, discontinuations and cost of all cellular and gene therapy products approved worldwide. Data and Methods We conducted an electronic search of approved cell and gene therapy products from the databases of the main drug regulatory agencies including the US Food and Drug Administration, the European Medicines Agency (EMA), the Korea Ministry of Food and Drug Safety (MFDS), and Japan’s Pharmaceuticals and Medical Devices Agency, China Food and Drug Administration, Ministry of Health and Social Development-Russia, Health Canada, and the Food and Drug Administration of the Philippines. We also searched the literature using MEDLINE/PubMed, Cochrane Library, Google Scholar and EMBASE databases. Cost information from the US was derived from the Reb Book (Truven Health Analytics). Costs from Europe were derived from Health Technology Assessments and from public sector, financial news and company’s web pages. Where available, we also obtained cost for products approved in other countries from public sector, financial news and company’s web pages. All cost data were converted to USD. Results There were 52 cell and gene therapy products marketed in the world as of September 2018. Of these, 39 (75.0%) were cell therapy medicinal products and 13 (25.0%) were gene therapy medicinal products. Of the approved products, 29 (74.3%) cell and 8 (61.5%) gene therapy products were first approved in the past 10 years (2008-present). Korea had the greatest number of approved cellular therapy-19 followed by US-12, Japan -4, Europe -3 and Canada -1. While Europe had the highest number of approved gene therapies - 5 followed by US - 3, China -2 and Korea, Russia and Philippines one each. Overall, 8 (66.7%) of the approved gene therapy products were granted orphan designation. Three products approved by the EMA were withdrawn or discontinued from the market. Of them, 2 remain currently marketed in the US. Cost of treatment from Gene therapy in US ranged from $447600 to$1,020,000 while in Europe the range was $370000 to$962890. Gene therapies outside US and Europe were relatively cheaper. Cell therapies in North America had a price range from $30,370-$200,000, European cell therapies ranged from $17,658-$105,000. Conclusion In the study period, more autologous cell therapy products were approved than allogenic agents. The cost of gene and cell therapy drugs is much higher in the EU and North America in comparison to Asia. Majority of the gene therapies received orphan designation by the regulatory authorities and had conditional approvals while less than a quarter of cellular therapies received the orphan designation. Most of the gene therapies are approved for rare diseases with smaller patient population, companies find it difficult to make profits which results in market withdrawal of the therapies

The young open cluster NGC 7067 using Stromgren photometry

© The Authors 2016. Published by Oxford University Press on behalf of The Royal Astronomical Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. M. Monguio et al, ' The young open cluster NGC 7067 using Stromgren photometry ', MNRAS Vol 466(3): 3636-3647 (2017), first published online 17 December 2016, the version of record is available online via doi: 10.1093/mnras/stw3302NGC 7067 is a young open cluster located in the direction between the first and the second Galactic quadrants and close to the Perseus spiral arm. This makes it useful for studies of the nature of the Milky Way spiral arms. Stromgren photometry taken with the Wide Field Camera at the Isaac Newton Telescope allowed us to compute individual physical parameters for the bserved stars and hence to derive cluster’s physical parameters. Spectra from the 1.93-m telescope at the Observatoire de Haute-Provence helped to check and improve the results. We obtained photometry for 1233 stars, individual physical parameters for 515 and spectra for 9 of them. The 139 selected cluster members lead to a cluster distance of 4.4±0.4 kpc, with an age below log10(t(yr))=7.3 and a present Mass of 1260±160M⊙. The morphology of the data reveals that the centre of the cluster is at (α,δ)=(21: 24: 13.69,+48: 00: 39.2) J2000, with a radius of 6.′1. Stromgren and spectroscopic data allowed us to improve the previous parameters available for the cluster in the literature.Peer reviewedFinal Published versio

The Gaia spectrophotometric standard stars survey. I. Preliminary results

We describe two ground based observing campaigns aimed at building a grid of approximately 200 spectrophotometric standard stars (SPSS), with an internal ~1% precision and tied to Vega within ~3%, for the absolute flux calibration of data gathered by Gaia, the ESA astrometric mission. The criteria for the selection and a list of candidates are presented, together with a description of the survey strategy and the adopted data analysis methods. We also discuss a short list of notable rejected SPSS candidates and difficult cases, based on identification problems, literature discordant data, visual companions, and variability. In fact, all candidates are also monitored for constancy (within \pm5 mmag, approximately). In particular, we report on a CALSPEC standard, 1740346, that we found to be a delta Scuti variable during our short-term monitoring (1-2 h) campaign.Comment: 16 pages, 4 tables, 9 figures, accepted for publication by MNRAS on 20 July 201

International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19

STATEMENT: The International Society for Cellular and Gene Therapies (ISCT) and the International Society for Extracellular Vesicles (ISEV) recognize the potential of extracellular vesicles (EVs, including exosomes) from mesenchymal stromal cells (MSCs) and possibly other cell sources as treatments for COVID-19. Research and trials in this area are encouraged. However, ISEV and ISCT do not currently endorse the use of EVs or exosomes for any purpose in COVID-19, including but not limited to reducing cytokine storm, exerting regenerative effects or delivering drugs, pending the generation of appropriate manufacturing and quality control provisions, pre-clinical safety and efficacy data, rational clinical trial design and proper regulatory oversight

Influence of hypothermia on right atrial cardiomyocyte apoptosis in patients undergoing aortic valve replacement

BACKGROUND: There is increasing evidence that programmed cell death can be triggered during cardiopulmonary bypass (CPB) and may be involved in postoperative complications. The purpose of this study was to investigate whether apoptosis occurs during aortic valve surgery and whether modifying temperature during CPB has any influence on cardiomyocyte apoptotic death rate. METHODS: 20 patients undergoing elective aortic valve replacement for aortic stenosis were randomly assigned to either moderate hypothermic (ModHT group, n = 10, 28°C) or mild hypothermic (MiHT group, n = 10, 34°C) CPB. Myocardial samples were obtained from the right atrium before and after weaning from CPB. Specimens were examined for apoptosis by flow cytometry analysis of annexin V-propidium iodide (PI) and Fas death receptor staining. RESULTS: In the ModHT group, non apoptotic non necrotic cells (annexin negative, PI negative) decreased after CPB, while early apoptotic (annexin positive, PI negative) and late apoptotic or necrotic (PI positive) cells increased. In contrast, no change in the different cell populations was observed over time in the MiHT group. Fas expression rose after reperfusion in the ModHT group but not in MiHT patients, in which there was even a trend for a lower Fas staining after CPB (p = 0.08). In ModHT patients, a prolonged ischemic time tended to induce a higher increase of Fas (p = 0.061). CONCLUSION: Our data suggest that apoptosis signal cascade is activated at early stages during aortic valve replacement under ModHT CPB. This apoptosis induction can effectively be attenuated by a more normothermic procedure

Percentage of Patients with Preventable Adverse Drug Reactions and Preventability of Adverse Drug Reactions – A Meta-Analysis

BACKGROUND: Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients. METHODS: Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO's or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted. RESULTS: Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2-3.2%) had preventable adverse drug reactions and 52% (95% CI: 42-62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1-51%) had preventable adverse drug reactions and 45% (95% CI: 33-58%) of adverse drug reactions were preventable. CONCLUSIONS: This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research

Gaia Focused Product Release: A catalogue of sources around quasars to search for strongly lensed quasars

Context. Strongly lensed quasars are fundamental sources for cosmology. The Gaia space mission covers the entire sky with the unprecedented resolution of $0.18$" in the optical, making it an ideal instrument to search for gravitational lenses down to the limiting magnitude of 21. Nevertheless, the previous Gaia Data Releases are known to be incomplete for small angular separations such as those expected for most lenses. Aims. We present the Data Processing and Analysis Consortium GravLens pipeline, which was built to analyse all Gaia detections around quasars and to cluster them into sources, thus producing a catalogue of secondary sources around each quasar. We analysed the resulting catalogue to produce scores that indicate source configurations that are compatible with strongly lensed quasars. Methods. GravLens uses the DBSCAN unsupervised clustering algorithm to detect sources around quasars. The resulting catalogue of multiplets is then analysed with several methods to identify potential gravitational lenses. We developed and applied an outlier scoring method, a comparison between the average BP and RP spectra of the components, and we also used an extremely randomised tree algorithm. These methods produce scores to identify the most probable configurations and to establish a list of lens candidates. Results. We analysed the environment of 3 760 032 quasars. A total of 4 760 920 sources, including the quasars, were found within 6" of the quasar positions. This list is given in the Gaia archive. In 87\% of cases, the quasar remains a single source, and in 501 385 cases neighbouring sources were detected. We propose a list of 381 lensed candidates, of which we identified 49 as the most promising. Beyond these candidates, the associate tables in this Focused Product Release allow the entire community to explore the unique Gaia data for strong lensing studies further.Comment: 35 pages, 60 figures, accepted for publication by Astronomy and Astrophysic

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

© 2024 The Authors. Journal of Extracellular Vesicles, published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.Peer reviewe