Sensors and Actuators for the Advanced LIGO+ Upgrade

Advanced Laser Interferometer Gravitational-wave Observatory (LIGO A+) is a major upgrade to LIGO—the Laser Interferometer Gravitational-wave Observatory. For the A+ project, we have developed, produced, and characterized sensors and electronics to interrogate new optical suspensions designed to isolate optics from vibrations. The central element is a displacement sensor with an integrated electromagnetic actuator known as a BOSEM (Birmingham Optical Sensor and ElectroMagnetic actuator) and its readout and drive electronics required to integrate them into LIGO’s control and data system. In this paper, we report on the improvements to the sensors and the testing procedures undertaken to meet the enhanced performance requirements set out by the A+ upgrade to the detectors. The best devices reach a noise level of 4.5 ×10−11m/√Hz at a measurement frequency of 1 Hz, an improvement of 6.7 times over standard devices

FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy

Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention

Kank Is an EB1 Interacting Protein that Localises to Muscle-Tendon Attachment Sites in Drosophila

Little is known about how microtubules are regulated in different cell types during development. EB1 plays a central role in the regulation of microtubule plus ends. It directly binds to microtubule plus ends and recruits proteins which regulate microtubule dynamics and behaviour. We report the identification of Kank, the sole Drosophila orthologue of human Kank proteins, as an EB1 interactor that predominantly localises to embryonic attachment sites between muscle and tendon cells. Human Kank1 was identified as a tumour suppressor and has documented roles in actin regulation and cell polarity in cultured mammalian cells. We found that Drosophila Kank binds EB1 directly and this interaction is essential for Kank localisation to microtubule plus ends in cultured cells. Kank protein is expressed throughout fly development and increases during embryogenesis. In late embryos, it accumulates to sites of attachment between muscle and epidermal cells. A kank deletion mutant was generated. We found that the mutant is viable and fertile without noticeable defects. Further analysis showed that Kank is dispensable for muscle function in larvae. This is in sharp contrast to C. elegans in which the Kank orthologue VAB-19 is required for development by stabilising attachment structures between muscle and epidermal cells

Future enhanced clinical role of pharmacists in emergency departments in England:multi-site observational evaluation

Background There are concerns about maintaining appropriate clinical staffing levels in Emergency Departments. Pharmacists may be one possible solution. Objective To determine if Emergency Department attendees could be clinically managed by pharmacists with or without advanced clinical practice training. Setting Prospective 49 site cross-sectional observational study of patients attending Emergency Departments in England. Method Pharmacist data collectors identified patient attendance at their Emergency Department, recorded anonymized details of 400 cases and categorized each into one of four possible options: cases which could be managed by a community pharmacist; could be managed by a hospital pharmacist independent prescriber; could be managed by a hospital pharmacist independent prescriber with additional clinical training; or medical team only (unsuitable for pharmacists to manage). Impact indices sensitive to both workload and proportion of pharmacist manageable cases were calculated for each clinical group. Main outcome measure Proportion of cases which could be managed by a pharmacist. Results 18,613 cases were observed from 49 sites. 726 (3.9%) of cases were judged suitable for clinical management by community pharmacists, 719 (3.9%) by pharmacist prescribers, 5202 (27.9%) by pharmacist prescribers with further training, and 11,966 (64.3%) for medical team only. Impact Indices of the most frequent clinical groupings were general medicine (13.18) and orthopaedics (9.69). Conclusion The proportion of Emergency Department cases that could potentially be managed by a pharmacist was 36%. Greatest potential for pharmacist management was in general medicine and orthopaedics (usually minor trauma). Findings support the case for extending the clinical role of pharmacists

Management and outcomes of gastrointestinal congenital anomalies in low, middle and high income countries: Protocol for a multicentre, international, prospective cohort study

Introduction Congenital anomalies are the fifth leading cause of death in children <5 years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low and middle income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research Collaboration aims to undertake the first multicentre, international, prospective cohort study of a selection of common congenital anomalies comparing management and outcomes between low, middle and high income countries (HICs) globally. Methods and analysis The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung''s disease). Patient recruitment will be for a minimum of 1 month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre. The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of postoperative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. Ethics and dissemination At the host centre, this study is classified as an audit not requiring ethical approval. All participating collaborators have gained local approval in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for open access publication in a peer reviewed journal

Population of Merging Compact Binaries Inferred Using Gravitational Waves through GWTC-3

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star-black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc-3 yr-1 and the neutron star-black hole merger rate to be between 7.8 and 140 Gpc-3 yr-1, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc-3 yr-1 at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)κ with κ=2.9-1.8+1.7 for z≲1. Using both binary neutron star and neutron star-black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2-0.2+0.1 to 2.0-0.3+0.3M⊙. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3-0.5+0.3 and 27.9-1.8+1.9M⊙. While we continue to find that the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M⊙, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χi≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum

Evaluation of a novel nanocrystalline hydroxyapatite paste Ostim® in comparison to Alpha-BSM® - more bone ingrowth inside the implanted material with Ostim® compared to Alpha BSM®

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the performance a newly developed nanocrystalline hydroxyapatite, OSTIM^®following functional implantation in femoral sites in thirty-eight sheep for 1, 2 or 3 months. Ostim^®35 was compared to an established calcium phosphate, Alpha BSM^®.</p> <p>Methods</p> <p>Biomechanical testing, μ-CT analysis, histological and histomorphological analyses were conducted to compare the treatments including evaluation of bone regeneration level, material degradation, implant biomechanical characteristics.</p> <p>Results</p> <p>The micro-computed tomography (μCT) analysis and macroscopic observations showed that Ostim^®seemed to diffuse easily particularly when the defects were created in a cancellous bone area. Alpha BSM^®remained in the defect.</p> <p>The performance of Ostim was good in terms of mechanical properties that were similar to Alpha BSM^®and the histological analysis showed that the bone regeneration was better with Ostim^®than with Alpha BSM^®. The histomorphometric analysis confirmed the qualitative analysis and showed more bone ingrowth inside the implanted material with Ostim^®when compared to Alpha BSM ^®at all time points.</p> <p>Conclusions</p> <p>The successful bone healing with osseous consolidation verifies the importance of the nanocrystalline hydroxyapatite in the treatment of metaphyseal osseous volume defects in the metaphyseal spongiosa.</p

A joint fermi-gbm and ligo/virgo analysis of compact binary mergers from the first and second gravitational-wave observing runs

We present results from offline searches of Fermi Gamma-ray Burst Monitor (GBM) data for gamma-ray transients coincident with the compact binary coalescences observed by the gravitational-wave (GW) detectors Advanced LIGO and Advanced Virgo during their first and second observing runs. In particular, we perform follow-up for both confirmed events and low significance candidates reported in the LIGO/Virgo catalog GWTC-1. We search for temporal coincidences between these GW signals and GBM-triggered gamma-ray bursts (GRBs). We also use the GBM Untargeted and Targeted subthreshold searches to find coincident gamma-rays below the onboard triggering threshold. This work implements a refined statistical approach by incorporating GW astrophysical source probabilities and GBM visibilities of LIGO/Virgo sky localizations to search for cumulative signatures of coincident subthreshold gamma-rays. All search methods recover the short gamma-ray burst GRB 170817A occurring ∼1.7 s after the binary neutron-star merger GW170817. We also present results from a new search seeking GBM counterparts to LIGO single-interferometer triggers. This search finds a candidate joint event, but given the nature of the GBM signal and localization, as well as the high joint false alarm rate of 1.1 10-6 Hz, we do not consider it an astrophysical association. We find no additional coincidences

Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages