The consequences of dwarf galaxies colliding with the Milky Way

I simulate the collision of satellite galaxies with the Milky Way and observe the effects that this has on the orbits of the globular cluster populations within both the Milky Way and the satellite galaxies. This is done in order to investigate whether some of the Milky Way's globular clusters could have been donated from satellite galaxies which have been tidally stripped, since it is believed that the Sagittarius dwarf spheroidal galaxy is being tidally disrupted and that some of its globular clusters have been tidally stripped from it (such as Pal 12 and NGC 4147). It is also believed that there have been other Sagittarius-like satellite galaxies in the past which have donated globular clusters to the Milky Way. From a simulation of the 63 Casetti-Dinescu globular clusters orbiting in the Milky Way, I find that most of the encounters between the globular clusters occur at separations between 0.1 kpc and 10 kpc. I also find that there are approximately 24 (0.64%) collisions that may occur between the globular clusters in the next 10 Gyr. However some of these 24 collisions involve the same globular cluster (for example NGC 2808 which has 7 collisions). I vary the initial position values of the globular cluster pair which has the closest encounter, and I find that the collision is very dependant upon the initial conditions of the globular clusters. I then include the classical satellite galaxies in a simulation with the 63 globular clusters, and I find that most of the encounters between the satellite galaxies and the globular clusters occur at separations between 1 kpc and 10 kpc. However there is one encounter with a separation of 227 pc, this is between the SMC and NGC 7006, which has a probability of 1 for occurring in the next 10 Gyr. I also find that there are 10 (1.44%) collisions between the satellite galaxies and the globular clusters that may occur in the next 10 Gyr. The only satellite galaxies that are involved however are the Sagittarius dwarf galaxy, the LMC and the SMC. I generate 500 random Sagittarius-like satellite galaxies based upon the initial conditions of the Sagittarius dwarf galaxy, and I generate 500 random globular clusters. I simulate 10 randomly selected Sagittarius-like satellite galaxies, each containing 10 randomly selected globular clusters which are initially on circular orbits around their host galaxy, and the globular clusters have spacings from their host galaxy in steps of 0.45 kpc. The simulated dwarf galaxies use a decreasing mass function, and I find that after 1 Gyr they have lost all of their globular clusters to the Milky Way. I continue this simulation for a further 10 Gyr, and upon investigation of some of the globular clusters' properties (eccentricity, j_z, orbital energy, and pericentre-apocentre distances), and compare them to the globular clusters from the Casetti-Dinescu database. I find that there are 5 (8%) Casetti-Dinescu globular clusters which have similar properties to the accreted globular clusters from the Sagittarius-like satellite galaxies. These are NGC 1851, NGC 3201, NGC 4590, NGC 7006, and Pal 13. In appendix 3 I run a more realistic simulation and find that there are 6 (~10%) Casetti-Dinescu globular clusters which have similar properties to the accreted globular clusters from the Sagittarius-like satellite galaxies. These are NGC 1851, NGC 4147, NGC 4590, NGC 5024, NGC 6205, NGC 6284. I also calculate that if we have two Sagittarius-like satellite galaxies orbiting within the Milky Way every 5 Gyr and they each donate 9 globular clusters, then this means that 36 - 45 (23 - 29%) of the Milky Way's globular cluster population may have come from tidal stripping events (i.e. 4 - 5 Sagittarius-like satellite galaxies). This is in good agreement with Forbes et al., (2010), van den Bergh (2000), and Mackey & Gilmore (2004), who suggested that there were 27 - 47, 35, and 41 globular clusters which were accreted from satellite galaxies respectively. I believe that the 9 globular clusters previously mention are members of the 36 - 45 globular clusters that have been accreted in the Milky Way's history

"It's something you have to put up with' - service users' experiences of in utero transfer: a qualitative study

Objective The purpose of this study was to gain in-depth insight and enhance understanding of service users’ experiences of the in utero transfer (IUT) process, in order to inform policy and improve the current service provision of maternal care. Design Qualitative descriptive study using semi-structured interviews. Setting Participant's home or hospital in the Midlands, UK. Population Fifteen women transferred in utero to a tertiary level maternity hospital; five male partners and two grandmothers. Methods Audio-recorded individual or paired semi-structured interviews transcribed verbatum and analysed thematically using nvivo 9. Main outcome measures Facilitators and barriers of the IUT experience. Results Findings suggest that IUT is an emotional experience that financially disadvantages patients and their families. Male partners were perceived to be most negatively affected by the experience. The quality of the IUT experience was influenced by a range of factors, including the lack of proximity to home and the lack of information. Patients had little knowledge or awareness of IUT, and most felt unprepared for displacement. Despite this, there was resigned acceptance that IUT was a necessary rather than adverse experience. Conclusions The experience of IUT for service users could be enhanced by ensuring that they are better informed about the process and the circumstances that necessitate displacement, that they are better informed about the hospital to which they are being transferred, and that they are transferred as close to home as possible. Efforts to minimise the emotional and socio-economic impact of IUT on women and their families also need to be considered

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2×/day, s.c.) from 20 to 30 days post-gestational age followed by brief noise exposure (110 dB SPL; 4–45 kHz, 30 s) would show greater noise-induced permanent threshold shifts (NIPTS) than mice receiving either treatment alone. Noise exposure produced 30–40 dB of NIPTS and moderate hair cell loss in young saline-treated mice. KM alone at this dose had no effect on thresholds. Surprisingly, mice receiving KM plus noise were protected from NIPTS, showing ABR thresholds not significantly different from unexposed controls. Mice receiving KM prior to noise exposure also showed significantly less outer hair cell loss than saline-treated mice. Additional experiments indicated protection by KM when the noise was applied either 24 or 48 h after the last KM injection. Our results demonstrate a powerful protective effect of sub-chronic low-dose kanamycin against NIPTS in young CBA/J mice. Repeated kanamycin exposure may establish a preconditioned protective state, the molecular bases of which remain to be determined