Study Protocol. ECSSIT – Elective Caesarean Section Syntocinon® Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon®) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section

<p>Abstract</p> <p>Background</p> <p>Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death.</p> <p>The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4–10 minutes) therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion.</p> <p>Methods and design</p> <p>A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml). A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha.</p> <p>Discussion</p> <p>It is both important and timely that we evaluate the optimal approach to the management of the third stage at elective caesarean section. Safe operative delivery is now a priority and a reality for many pregnant women. Obstetricians, obstetric anaesthetists, midwives and pregnant women need high quality evidence on which to base management approaches. The overall aim is to reduce maternal haemorrhagic morbidity and its attendant risks at elective caesarean section.</p> <p>Trial registration</p> <p>number: ISRCTN17813715</p

Wear of highly crosslinked polyethylene acetabular components: a review of RSA studies

Background and purpose - Wear rates of highly crosslinked polyethylene (XLPE) acetabular components have varied considerably between different published studies. This variation is in part due to the different techniques used to measure wear and to the errors inherent in measuring the relatively low amounts of wear in XLPE bearings. We undertook a scoping review of studies that have examined the in vivo wear of XLPE acetabular components using the most sensitive method available, radiostereometric analysis (RSA). Methods - A systematic search of the PubMed, Scopus, and Cochrane databases was performed to identify published studies in which RSA was used to measure wear of XLPE components in primary total hip arthroplasty (THA). Results - 18 publications examined 12 primary THA cohorts, comprising only 260 THAs at 2-10 years of follow-up. The mean or median proximal wear rate reported ranged from 0.00 to 0.06 mm/year. However, differences in the manner in which wear was determined made it difficult to compare some studies. Furthermore, differences in RSA methodology between studies, such as the use of supine or standing radiographs and the use of beaded or unbeaded reference segments, may limit future meta-analyses examining the effect of patient and implant variables on wear rates. Interpretation - This scoping review confirmed the low wear rates of XLPE in THA, as measured by RSA. We make recommendations to enhance the standardization of reporting of RSA wear results, which will facilitate early identification of poorly performing implants and enable a better understanding of the effects of surgical and patient factors on wear.Stuart A Callary, Lucian B Solomon, Oksana T Holubowycz, David G Campbell, Zachary Munn, and Donald W Howi

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

The Ecological Importance of Unregulated Tributaries to Macroinvertebrate Diversity and Community Composition in a Regulated River

In regulated rivers, dams alter longitudinal gradients in flow regimes, geomorphology, water quality and temperature with associated impacts on aquatic biota. Unregulated tributaries can increase biodiversity in regulated environments by contributing colonists to the main channel and creating transitional habitats at a stream junction. We assessed whether unregulated tributaries influence macroinvertebrate communities in two mainstem rivers during summer low-flows. Three tributary junctions of upland cobble-gravel bed streams were surveyed in an unregulated and a regulated river in the Sierra Nevada Mountains, California, USA. We found distinct physical habitat conditions and increased macroinvertebrate abundance and diversity in unregulated tributaries on the regulated river, but macroinvertebrate diversity did not increase downstream of tributary junctions as predicted. On the unregulated river, macroinvertebrate diversity was similar in upstream, downstream and unregulated tributary sites. Our findings highlight that unregulated tributaries support high macroinvertebrate diversity and heterogeneous communities compared to the mainstem sites in a regulated river, and thus likely support ecological processes, such as spillover predation, breeding and refugia use for mobile taxa. We suggest unregulated tributaries are an integral component of river networks, serving as valuable links in the landscape for enhancing biodiversity, and should be protected in conservation and management plans

A systematic review of non-invasive modalities used to identify women with anal incontinence symptoms after childbirth

© 2018, The International Urogynecological Association. Introduction and hypothesis: Anal incontinence following childbirth is prevalent and has a significant impact upon quality of life (QoL). Currently, there is no standard assessment for women after childbirth to identify these symptoms. This systematic review aimed to identify non-invasive modalities used to identify women with anal incontinence following childbirth and assess response and reporting rates of anal incontinence for these modalities. Methods: Ovid Medline, Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Collaboration, EMBASE and Web of Science databases were searched for studies using non-invasive modalities published from January 1966 to May 2018 to identify women with anal incontinence following childbirth. Study data including type of modality, response rates and reported prevalence of anal incontinence were extracted and critically appraised. Results: One hundred and nine studies were included from 1602 screened articles. Three types of non-invasive modalities were identified: validated questionnaires/symptom scales (n = 36 studies using 15 different instruments), non-validated questionnaires (n = 50 studies) and patient interviews (n = 23 studies). Mean response rates were 92% up to 6 weeks after childbirth. Non-personalised assessment modalities (validated and non-validated questionnaires) were associated with reporting of higher rates of anal incontinence compared with patient interview at all periods of follow-up after childbirth, which was statistically significant between 6 weeks and 1 year after childbirth (p < 0.05). Conclusions: This systematic review confirms that questionnaires can be used effectively after childbirth to identify women with anal incontinence. Given the methodological limitations associated with non-validated questionnaires, assessing all women following childbirth for pelvic-floor symptomatology, including anal incontinence, using validated questionnaires should be considered