Publications by authors named "Edward Morris"

171 Publications

Effects of the COVID-19 pandemic on maternal and perinatal outcomes: a systematic review and meta-analysis.

Lancet Glob Health 2021 Mar 31. Epub 2021 Mar 31.

Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, UK. Electronic address:

Background: The COVID-19 pandemic has had a profound impact on health-care systems and potentially on pregnancy outcomes, but no systematic synthesis of evidence of this effect has been undertaken. We aimed to assess the collective evidence on the effects on maternal, fetal, and neonatal outcomes of the pandemic.

Methods: We did a systematic review and meta-analysis of studies on the effects of the pandemic on maternal, fetal, and neonatal outcomes. We searched MEDLINE and Embase in accordance with PRISMA guidelines, from Jan 1, 2020, to Jan 8, 2021, for case-control studies, cohort studies, and brief reports comparing maternal and perinatal mortality, maternal morbidity, pregnancy complications, and intrapartum and neonatal outcomes before and during the pandemic. We also planned to record any additional maternal and offspring outcomes identified. Studies of solely SARS-CoV-2-infected pregnant individuals, as well as case reports, studies without comparison groups, narrative or systematic literature reviews, preprints, and studies reporting on overlapping populations were excluded. Quantitative meta-analysis was done for an outcome when more than one study presented relevant data. Random-effects estimate of the pooled odds ratio (OR) of each outcome were generated with use of the Mantel-Haenszel method. This review was registered with PROSPERO (CRD42020211753).

Findings: The search identified 3592 citations, of which 40 studies were included. We identified significant increases in stillbirth (pooled OR 1·28 [95% CI 1·07-1·54]; I=63%; 12 studies, 168 295 pregnancies during and 198 993 before the pandemic) and maternal death (1·37 [1·22-1·53; I=0%, two studies [both from low-income and middle-income countries], 1 237 018 and 2 224 859 pregnancies) during versus before the pandemic. Preterm births before 37 weeks' gestation were not significantly changed overall (0·94 [0·87-1·02]; I=75%; 15 studies, 170 640 and 656 423 pregnancies) but were decreased in high-income countries (0·91 [0·84-0·99]; I=63%; 12 studies, 159 987 and 635 118 pregnancies), where spontaneous preterm birth was also decreased (0·81 [0·67-0·97]; two studies, 4204 and 6818 pregnancies). Mean Edinburgh Postnatal Depression Scale scores were higher, indicating poorer mental health, during versus before the pandemic (pooled mean difference 0·42 [95% CI 0·02-0·81; three studies, 2330 and 6517 pregnancies). Surgically managed ectopic pregnancies were increased during the pandemic (OR 5·81 [2·16-15·6]; I=26%; three studies, 37 and 272 pregnancies). No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; hypertensive disorders of pregnancy; preterm birth before 34 weeks', 32 weeks', or 28 weeks' gestation; iatrogenic preterm birth; labour induction; modes of delivery (spontaneous vaginal delivery, caesarean section, or instrumental delivery); post-partum haemorrhage; neonatal death; low birthweight (<2500 g); neonatal intensive care unit admission; or Apgar score less than 7 at 5 min.

Interpretation: Global maternal and fetal outcomes have worsened during the COVID-19 pandemic, with an increase in maternal deaths, stillbirth, ruptured ectopic pregnancies, and maternal depression. Some outcomes show considerable disparity between high-resource and low-resource settings. There is an urgent need to prioritise safe, accessible, and equitable maternity care within the strategic response to this pandemic and in future health crises.

Funding: None.
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http://dx.doi.org/10.1016/S2214-109X(21)00079-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012052PMC
March 2021

What happens to female sexual function during pregnancy?

Eur J Obstet Gynecol Reprod Biol 2021 Mar 15;258:265-268. Epub 2021 Jan 15.

Norfolk and Norwich University Hospital, Colney Lane, Norwich, NR4 7UY, United Kingdom.

Introduction: Female sexual function remains an under-investigated and neglected topic in medical research. Studies have found a strong association between female sexual dysfunction (FSD) and decreased physical, emotional and overall life satisfaction [1]. Although FSD and the impact it has on quality of life is becoming increasingly recognised, the effect of pregnancy on FSD is relatively under-researched.

Methods: Based on a significance level of 5% and a study power of 80 % a power calculation was performed using an assumed 20 % loss to follow up rate. 85 primiparous women with singleton pregnancies were recruited at their dating scan and asked to complete the Female Sexual Function Index (FSFI) questionnaire in each trimester. The total score and the six domains (pain, satisfaction, orgasm, desire, lubrication and desire) were compared with Friedman's ANOVA. The validated cut-off score of 26.55 was used to diagnose FSD.

Results: There was an overall decrease in total FSFI scores across the three trimesters, from a median full-scale score of 27.5 in the first trimester, to 24.7 in the second and 21.4 in the third trimester. There was a very significant decrease in all scores (the full scale score and the six domains- desire, lubrication, arousal, orgasm, satisfaction and pain), from the first trimester to the third trimester with each outcome (p < 0.0001). There were 30 women with FDS in the first trimester, 50 in the second and 68 in the third (p < 0.05).

Conclusions: For primiparous women pregnancy appears to have a negative impact on sexual function with 86.1 % of women being classified as suffering from FSD in the third trimester. The importance of sexual function in overall quality life is well known and so it is important that the changes experienced by women and their partners are discussed by doctors with their patients.
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http://dx.doi.org/10.1016/j.ejogrb.2021.01.003DOI Listing
March 2021

Structure of human RNA polymerase III.

Nat Commun 2020 12 17;11(1):6409. Epub 2020 Dec 17.

Division of Structural Biology, The Institute of Cancer Research, London, SW7 3RP, UK.

In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III transcription is observed in cancer and causative Pol III mutations have been described in neurodevelopmental disorders and hypersensitivity to viral infection. Here, we report a cryo-EM reconstruction at 4.0 Å of human Pol III, allowing mapping and rationalization of reported genetic mutations. Mutations causing neurodevelopmental defects cluster in hotspots affecting Pol III stability and/or biogenesis, whereas mutations affecting viral sensing are located in proximity to DNA binding regions, suggesting an impairment of Pol III cytosolic viral DNA-sensing. Integrating x-ray crystallography and SAXS, we also describe the structure of the higher eukaryote specific RPC5 C-terminal extension. Surprisingly, experiments in living cells highlight a role for this module in the assembly and stability of human Pol III.
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http://dx.doi.org/10.1038/s41467-020-20262-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747717PMC
December 2020

Women's perceptions of COVID-19 and their healthcare experiences: a qualitative thematic analysis of a national survey of pregnant women in the United Kingdom.

BMC Pregnancy Childbirth 2020 Oct 7;20(1):600. Epub 2020 Oct 7.

Norfolk & Norwich University Hospital, Colney Lane, Norwich, NR47UY, UK.

Background: The aim of this national survey was to explore pregnant women's perceptions of COVID-19 and their healthcare experiences.

Methods: Through patient and public involvement, a questionnaire was developed and advertised via the BBC website, Twitter and other online media during May 2020. The findings were analysed by qualitative thematic analysis. Women who are currently pregnant, or who have delivered during the COVID-19 pandemic were invited to partake in a national online survey.

Results: One thousand four hundred fifty-one participants replied to the online questionnaire. Participants provided significant insight into the perceived barriers to seeking healthcare during this pandemic. These include 'not wanting to bother anyone', 'lack of wider support from allied healthcare workers' and the influence of the media. Other concerns included the use of virtual clinics antenatally and their acceptability to patients, the presence of birthing partners, and the way in which information is communicated about rapidly changing and evolving services. The influence of the media has also had a significant impact on the way women perceive hospital care in light of COVID-19 and for some, this has shaped whether they would seek help.

Conclusions: This is the first ever reported study in the United Kingdom to explore pregnant women's perceptions of COVID-19 and their subsequent healthcare experiences. It has also provided insight into perceived barriers into seeking care as well as maternal concerns antenatally, intrapartum and postpartum.
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http://dx.doi.org/10.1186/s12884-020-03283-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539281PMC
October 2020

Exploring clinicians' perspectives on the 'Obstetric Anal Sphincter Injury Care Bundle' national quality improvement programme: a qualitative study.

BMJ Open 2020 09 9;10(9):e035674. Epub 2020 Sep 9.

Centre for Implementation Science, King's College London, London, UK.

Introduction: Obstetric anal sphincter injuries (OASI) can have severe debilitating consequences to women and health systems. The OASI Care Bundle quality improvement programme was introduced in 16 maternity units across England, Scotland and Wales (January 2017 to March 2018) to address increasing OASI rates.

Objectives: To explore clinicians' (midwives' and obstetricians') perspectives of the OASI Care Bundle with respect to (1) acceptability, (2) feasibility, and (3) sustainability.

Design: A qualitative exploratory study using focus groups methodology.

Setting: A total of 16 focus groups were conducted in 16 maternity units in England, Scotland and Wales where the OASI Care Bundle was implemented. Focus groups took place approximately 3 months following initial implementation of the care bundle in each unit.

Participants: A total of 101 clinicians participated, with an average of six per focus group. Participants volunteered to take part and compromised of 37 obstetricians and 64 midwives (including eight students). The majority were female and the mean age was 36.5 years.

Results: Four main themes emerged: 'Implementation strategies', 'Opportunities to use the OASI Care Bundle', 'Does current practice need to change?' and 'Perceptions of what women want'. Midwives were more likely than obstetricians to report themes alluding to 'what women want' and variations in intrapartum perineal protection techniques. Both professional groups reported similar views of other themes, in particular regarding the supporting clinical evidence. Gaps were identified in clinicians' knowledge and experience of intrapartum perineal management.

Conclusions: Adoption of the OASI Care Bundle was associated with a number of cognitive and interpersonal factors, such as personal values, interprofessional working and how the intervention was launched; which both facilitated and impeded adoption. The 'what women want' theme has implications for maternal autonomy and needs further exploration. Our findings can be used by similar initiatives to reduce perineal trauma both nationally and internationally.

Trial Registration Number: ISCTRN 12143325; https://doi.org/10.1186/ISRCTN12143325.
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http://dx.doi.org/10.1136/bmjopen-2019-035674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482496PMC
September 2020

SARS-CoV-2 infection in pregnancy: A systematic review and meta-analysis of clinical features and pregnancy outcomes.

EClinicalMedicine 2020 Aug 3;25:100446. Epub 2020 Jul 3.

School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.

Background: Perform a systematic review and meta-analysis of SARS-CoV-2 infection and pregnancy.

Methods: Databases (Medline, Embase, Clinicaltrials.gov, Cochrane Library) were searched electronically on 6th April and updated regularly until 8th June 2020. Reports of pregnant women with reverse transcription PCR (RT-PCR) confirmed COVID-19 were included. Meta-analytical proportion summaries and meta-regression analyses for key clinical outcomes are provided.

Findings: 86 studies were included, 17 studies (2567 pregnancies) in the quantitative synthesis; other small case series and case reports were used to extract rarely-reported events and outcome. Most women (73.9%) were in the third trimester; 52.4% have delivered, half by caesarean section (48.3%). The proportion of Black, Asian or minority ethnic group membership (50.8%); obesity (38.2%), and chronic co-morbidities (32.5%) were high. The most commonly reported clinical symptoms were fever (63.3%), cough (71.4%) and dyspnoea (34.4%). The commonest laboratory abnormalities were raised CRP or procalcitonin (54.0%), lymphopenia (34.2%) and elevated transaminases (16.0%). Preterm birth before 37 weeks' gestation was common (21.8%), usually medically-indicated (18.4%). Maternal intensive care unit admission was required in 7.0%, with intubation in 3.4%. Maternal mortality was uncommon (~1%). Maternal intensive care admission was higher in cohorts with higher rates of co-morbidities (beta=0.007, p<0.05) and maternal age over 35 years (beta=0.007, p<0.01). Maternal mortality was higher in cohorts with higher rates of antiviral drug use (beta=0.03, p<0.001), likely due to residual confounding. Neonatal nasopharyngeal swab RT-PCR was positive in 1.4%.

Interpretation: The risk of iatrogenic preterm birth and caesarean delivery was increased. The available evidence is reassuring, suggesting that maternal morbidity is similar to that of women of reproductive age. Vertical transmission of the virus probably occurs, albeit in a small proportion of cases.

Funding: N/A.
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http://dx.doi.org/10.1016/j.eclinm.2020.100446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334039PMC
August 2020

COVID-19 and ABO blood groups.

Transfusion 2020 08 1;60(8):1883-1884. Epub 2020 Aug 1.

Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1111/trf.15946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323215PMC
August 2020

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study.

BMJ 2020 06 8;369:m2107. Epub 2020 Jun 8.

National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.

Objectives: To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants.

Design: Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS).

Setting: All 194 obstetric units in the UK.

Participants: 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020.

Main Outcome Measures: Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission.

Results: The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth.

Conclusions: Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation.

Study Registration: ISRCTN 40092247.
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http://dx.doi.org/10.1136/bmj.m2107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277610PMC
June 2020

Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA.

Mol Cell 2020 07 22;79(1):99-114.e9. Epub 2020 May 22.

Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:

Structural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin I and II and unveil the architecture of the human condensin II complex, revealing two putative DNA-entrapment sites. Using single-molecule imaging, we demonstrate that both condensin I and II exhibit ATP-dependent motor activity and promote extensive and reversible compaction of double-stranded DNA. Nucleosomes are incorporated into DNA loops during compaction without being displaced from the DNA, indicating that condensin complexes can readily act upon nucleosome-bound DNA molecules. These observations shed light on critical processes involved in genome organization in human cells.
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http://dx.doi.org/10.1016/j.molcel.2020.04.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335352PMC
July 2020

Tidal elevation is the key factor modulating burial rates and composition of organic matter in a coastal wetland with multiple habitats.

Sci Total Environ 2020 Jul 24;724:138205. Epub 2020 Mar 24.

Departamento de Biología, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, Poligono Río San Pedro s/n, 11510, Puerto Real, Cádiz, Spain; Instituto Universitario de Investigación Marina (INMAR), Universidad de Cádiz, Campus de Excelencia Internacional del Mar (CEIMAR) Campus Universitario de Puerto Real, 11510, Puerto Real, Cádiz, Spain.

This study examines long-term burial rates of organic carbon (OC), organic nitrogen (ON), and total sulphur (TS) in a tidal-dominated coastal wetland with a high spatial heterogeneity and habitat diversity, and long history of human impacts, Cádiz Bay (SW Spain). Using replicate sediment cores, we quantified fluxes of these elements over a transect, extending from the lower saltmarsh (Spartina maritima, ~0.3 m mean sea level, MSL) to the lower intertidal region (Zostera noltei, ~ - 0.7 m MSL). Potential organic matter (OM) sources to the sediment were examined using an extensive dataset on carbon and nitrogen stable isotopes, and C:N molar ratios of primary producers in the region. OC burial rates decreased from the sites below MSL (~80 gC·m·y) to the lower saltmarsh (~50 gC·m·y), whereas ON burial rates showed an opposite pattern (~3 gN·m·y and ~4 gN·m·y observed below and above MSL, respectively). TS burial rates (0.5-46 gS·m·y) did not show any trend along the sea-land gradient. Hence, (tidal) elevation appeared to be an important determinant of sediment biogeochemical properties, and predictor of OM burial rates. The Bayesian mixing model suggested a well-mixed combination of subtidal and terrestrial/high-marsh OM sources to the surface sediments, with no clear indication of an increased contribution from the particular vegetation species inhabiting the sediments. The indication that there is substantial transport, remineralization and cycling of OM between habitats, suggests diversity may play an important role in maintaining this function, reinforcing the idea that a holistic, catchment-scale view is appropriate for understanding and preserving the long-term burial of OM in coastal wetlands.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138205DOI Listing
July 2020

UK HRT shortages, how can this be good for anybody?

Post Reprod Health 2020 03;26(1):3-4

Dumfries & Galloway Royal Infirmary, UK.

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http://dx.doi.org/10.1177/2053369120910693DOI Listing
March 2020

A Model of Differential Mammary Growth Initiation by Stat3 and Asymmetric Integrin-α6 Inheritance.

Cell Rep 2020 03;30(11):3605-3615.e5

Department of Integrative Oncology, BC Cancer Research Centre, BC Cancer Agency, Vancouver, BC, Canada; Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Multiple cancer-related genes both promote and paradoxically suppress growth initiation, depending on the cell context. We discover an explanation for how this occurs for one such protein, Stat3, based on asymmetric cell division. Here, we show that Stat3, by Stathmin/PLK-1, regulates mitotic spindle orientation, and we use it to create and test a model for differential growth initiation. We demonstrate that Integrin-α6 is polarized and required for mammary growth initiation. Spindles orient relative to polar Integrin-α6, dividing perpendicularly in normal cells and parallel in tumor-derived cells, resulting in asymmetric or symmetric Integrin-α6 inheritance, respectively. Stat3 inhibition randomizes spindle orientation, which promotes normal growth initiation while reducing tumor-derived growth initiation. Lipid raft disruption depolarizes Integrin-α6, inducing spindle-orientation-independent Integrin-α6 inheritance. Stat3 inhibition no longer affects the growth of these cells, suggesting Stat3 acts through the regulation of spindle orientation to control growth initiation.
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http://dx.doi.org/10.1016/j.celrep.2020.02.079DOI Listing
March 2020

Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.

Nat Commun 2020 02 28;11(1):1120. Epub 2020 Feb 28.

Signalling and Structural Biology Laboratory, Francis Crick Institute, NW1 1AT, London, UK.

The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated by DNA junction substrates is not currently understood. Here we report cryo-electron microscopy structures of both DNA-free and DNA-bound human XPF-ERCC1. DNA-free XPF-ERCC1 adopts an auto-inhibited conformation in which the XPF helical domain masks the ERCC1 (HhH) domain and restricts access to the XPF catalytic site. DNA junction engagement releases the ERCC1 (HhH) domain to couple with the XPF-ERCC1 nuclease/nuclease-like domains. Structure-function data indicate xeroderma pigmentosum patient mutations frequently compromise the structural integrity of XPF-ERCC1. Fanconi anaemia patient mutations in XPF often display substantial in-vitro activity but are resistant to activation by ICLR recruitment factor SLX4. Our data provide insights into XPF-ERCC1 architecture and catalytic activation.
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http://dx.doi.org/10.1038/s41467-020-14856-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048804PMC
February 2020

A 14-year retrospective analysis of indications and outcomes of autologous haemopoietic stem cell transplantation in regional Queensland: a single-centre experience.

Intern Med J 2020 02;50(2):214-221

Icon Group, Brisbane, Queensland, Australia.

Background: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies.

Aims: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards.

Methods: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed.

Results: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years.

Conclusion: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.
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http://dx.doi.org/10.1111/imj.14395DOI Listing
February 2020

Critical Masculinity Studies and Research on Violence Against Women: An Assessment of Past Scholarship and Future Directions.

Violence Against Women 2019 12;25(16):1980-2006

University of Kentucky, Lexington, USA.

This article investigates the role of critical masculinity theory on the field of violence against women (VAW). We conduct a meta-analysis to discern which theories of masculinity have been used within the journal over the past 25 years. This search revealed that many articles use masculinity concepts but do not always articulate explicit theories of masculinity. We review hegemonic masculinity and male peer support, two of the most commonly used theories of masculinity and violence. We then discuss new developments within masculinity scholarship, including theories of manhood acts, inclusive masculinity, and hybrid masculinity, and consider how these perspectives can enhance the already robust scholarship on masculinity and VAW.
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http://dx.doi.org/10.1177/1077801219875827DOI Listing
December 2019

The Interacting Head Motif Structure Does Not Explain the X-Ray Diffraction Patterns in Relaxed Vertebrate (Bony Fish) Skeletal Muscle and Insect () Flight Muscle.

Biology (Basel) 2019 Sep 14;8(3). Epub 2019 Sep 14.

Muscle Contraction Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.

Unlike electron microscopy, which can achieve very high resolution but to date can only be used to study static structures, time-resolved X-ray diffraction from contracting muscles can, in principle, be used to follow the molecular movements involved in force generation on a millisecond timescale, albeit at moderate resolution. However, previous X-ray diffraction studies of resting muscles have come up with structures for the head arrangements in resting myosin filaments that are different from the apparently ubiquitous interacting head motif (IHM) structures found by single particle analysis of electron micrographs of isolated myosin filaments from a variety of muscle types. This head organization is supposed to represent the super-relaxed state of the myosin filaments where adenosine triphosphate (ATP) usage is minimized. Here we have tested whether the interacting head motif structures will satisfactorily explain the observed low-angle X-ray diffraction patterns from resting vertebrate (bony fish) and invertebrate (insect flight) muscles. We find that the interacting head motif does not, in fact, explain what is observed. Previous X-ray models fit the observations much better. We conclude that the X-ray diffraction evidence has been well interpreted in the past and that there is more than one ordered myosin head state in resting muscle. There is, therefore, no reason to question some of the previous X-ray diffraction results on myosin filaments; time-resolved X-ray diffraction should be a reliable way to follow crossbridge action in active muscle and may be one of the few ways to visualise the molecular changes in myosin heads on a millisecond timescale as force is actually produced.
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http://dx.doi.org/10.3390/biology8030067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784062PMC
September 2019

Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome.

Nat Commun 2019 08 23;10(1):3814. Epub 2019 Aug 23.

Department of Chemistry, King's College London, 7 Trinity Street, London, SE1 1DB, UK.

Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members.
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http://dx.doi.org/10.1038/s41467-019-11772-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707232PMC
August 2019

Standardizing abdominal sacrocolpopexy for the treatment of apical prolapse: One year on.

Int J Gynaecol Obstet 2019 Oct 20;147(1):49-53. Epub 2019 Aug 20.

Gynaecology Department, Norfolk and Norwich University Hospital, Norwich, UK.

Objective: To determine the safety and efficacy of a standardized bilateral abdominal sacrocolpopexy using polyvinylidene fluoride mesh 1-year post-operatively.

Methods: In a retrospective observational study of women undergoing bilateral abdominal sacrocolpo/cervicopexy between July 2013 and October 2016 at the Norfolk and Norwich University Hospital, Norwich, UK, patients were assessed 1 year post-operatively using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS).

Results: The study involved 100 women, 93 of whom were followed up 1 year post-operatively. The primary outcome was apical prolapse rate, of which there were none. Eight women had anterior and four had posterior wall prolapses; four women required vaginal repairs. Eleven women complained of urinary stress incontinence (six worsening and five de novo) and five had subsequent tension-free vaginal tape procedures. One woman had urethral pain and one had mesh exposure into the vagina. Pre-operatively, mean ICIQ-VS score was 27.87 (standard deviation [SD] 6.8), and at 1 year post-operatively it was 5.82 (SD 3.8). Impact on quality of life score dropped by 83.4%, from 8.35 (SD 2.1) to 1.39 (SD 1.1).

Conclusion: The modified technique used in the present study retained the advantages of traditional sacrocolpopexy, but required smaller volumes of mesh. We found it to be safe and effective with excellent patient satisfaction at 1 year, and providing a promising treatment option for patients suffering from apical prolapse.
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http://dx.doi.org/10.1002/ijgo.12935DOI Listing
October 2019

Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle.

Proc Natl Acad Sci U S A 2019 07 18;116(31):15534-15539. Epub 2019 Jul 18.

Molecular Medicine Section, National Heart and Lung Institute, Imperial College London, SW7 2AZ London, United Kingdom;

Striated muscle enables movement in all animals by the contraction of myriads of sarcomeres joined end to end by the Z-bands. The contraction is due to tension generated in each sarcomere between overlapping arrays of actin and myosin filaments. At the Z-band, actin filaments from adjoining sarcomeres overlap and are cross-linked in a regular pattern mainly by the protein α-actinin. The Z-band is dynamic, reflected by the 2 regular patterns seen in transverse section electron micrographs; the so-called small-square and basketweave forms. Although these forms are attributed, respectively, to relaxed and actively contracting muscles, the basketweave form occurs in certain relaxed muscles as in the muscle studied here. We used electron tomography and subtomogram averaging to derive the 3D structure of the Z-band in the swimbladder sonic muscle of type I male plainfin midshipman fish (, into which we docked the crystallographic structures of actin and α-actinin. The α-actinin links run diagonally between connected pairs of antiparallel actin filaments and are oriented at an angle of about 25° away from the actin filament axes. The slightly curved and flattened structure of the α-actinin rod has a distinct fit into the map. The Z-band model provides a detailed understanding of the role of α-actinin in transmitting tension between actin filaments in adjoining sarcomeres.
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http://dx.doi.org/10.1073/pnas.1902235116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681754PMC
July 2019

A retrospective analysis of the prevalence and clinical outcomes of vitamin D deficiency in myeloma patients in tropical Australia.

Support Care Cancer 2020 Mar 21;28(3):1249-1254. Epub 2019 Jun 21.

Department of Haematology and Bone Marrow Transplantation, Townsville Hospital, 100 Angus Smith Drive, Douglas, Townsville, Queensland, 4814, Australia.

Purpose: The aim of this descriptive study was to assess the prevalence of vitamin D deficiency in patients on active therapy for multiple myeloma in a tropical climate. We also tested for the association of vitamin D status on clinical outcomes.

Methods: This was a single centre, observational study performed in Townsville, Australia, which has a sunlight heavy, tropical climate. Patients on active therapy for multiple myeloma underwent testing of serum 25-hydroxyvitamin D (25(OH)D). Information on disease stage, skeletal morbidity and symptoms of peripheral neuropathy were collected from medical records and self-reported patient questionnaires.

Results: A total of 41 patients were included. With a median disease duration of 38 months, 27% were found to be vitamin D deficient. Patients with vitamin D deficiency had a higher likelihood of peripheral neuropathy compared with their non-vitamin D counterparts (73% vs. 33%, P = 0.03). Although those with vitamin D deficiency had more skeletal morbidity, this was not statistically significant (73% vs 50%, P = 0.19). Reduced 25(OH) D was associated with a poor performance status (P = 0.003). There was no association between vitamin D status and stage of myeloma.

Conclusion: There is a relatively high prevalence of vitamin D deficiency in patients with myeloma in our study. This is despite a sunlight heavy, tropical climate. We report an association between vitamin D deficiency and peripheral neuropathy. Prospective interventional trials are required to further assess this.
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http://dx.doi.org/10.1007/s00520-019-04942-7DOI Listing
March 2020

A Safety Evaluation of the Impact of Maternity-Orientated Human Factors Training on Safety Culture in a Tertiary Maternity Unit.

J Patient Saf 2020 12;16(4):e359-e366

Clinical Fellow at the National Maternity and Perinatal Audit Royal College of Obstetricians and Gynaecologists (RCOG), London.

Background: Human factors have risen to attention in maternity as key contributors to patient harm. Despite national recommendation for multidisciplinary human factors training, there is a lack of guidance and healthcare-orientated training.

Objectives: The aim of the study was to evaluate the impact of maternity-orientated human factors training program on safety culture in a tertiary maternity unit.

Methods: This prospective observational cohort study was conducted for 6 months in a tertiary maternity unit. Participants involved in high-risk intrapartum care completed the Hospital Survey of Patient Safety Culture before and after intervention. Statistical analysis was performed using the χ test with statistical significance at 5% (P = 0.05).

Intervention: The human factors curriculum included situational awareness, communication, decision-making, conflict resolution, teamwork, and leadership. A train-the-trainer approach generated a faculty to disseminate multidisciplinary training. Traditional classroom teaching, social media content, and cognitive activities provided theoretical foundations. Forum theater and behavioral simulation taught complex communication issues. Regular labor ward simulations helped embed training into clinical practice.

Results: The results demonstrated statistically significant improvement in safety culture domains of communication openness, handover, nonpunitive response to error, and overall safety perception. Participants felt more able to challenge decisions or actions of those in authority, 33% responded "most of the time or always" in August increasing to 42% in January with a reduction of 50% in those responding "never" (P = 0.02). No change was found relating to team working, staffing or manager expectations promoting patient safety.

Conclusions: This study is proof-of-concept that maternity-orientated human factors training can improve safety culture.
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http://dx.doi.org/10.1097/PTS.0000000000000609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678659PMC
December 2020

Smokeless Tobacco and the Rural Teen: How Culture and Masculinity Contribute to Adolescent Use.

J Health Commun 2019 9;24(3):311-318. Epub 2019 Apr 9.

a Department of Communication , University of Kentucky , Lexington , USA.

Tobacco use is the leading preventable cause of disease, disability, and death in the United States. Smokeless tobacco (SLT) is primarily used by younger, rural males and often in the presence of other males. This formative study examined how hegemonic masculinity and male norms can lead to initiation and continued use of SLT by rural adolescent males and females. Survey data collected from high school sophomores in 4 rural high schools (n = 293) explores perceptions of masculinity and male norms' contribution to SLT uptake and use. About 22.5% of total sample reported lifetime use (34.4% male, 13.7% female), 10.9% reported past-month use (20.0% male, 4.2% female). Logistic regressions show a one-unit increase in adherence to traditional perceptions of masculinity more than doubled the odds of ever using SLT and significantly increased odds of 30-day use. Having male household family members who uses SLT significantly increased the odds of lifetime and 30-day SLT use for both genders, while having male family members who smoke cigarettes was not a significant correlate. Recognition of health warnings on SLT packaging was negatively associated with SLT use for both genders. Implications for inclusion of masculinity and male role models in SLT prevention intervention strategies are discussed.
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http://dx.doi.org/10.1080/10810730.2019.1601302DOI Listing
March 2020

A computer-based simulation of childbirth using the partial Dirichlet-Neumann contact method with total Lagrangian explicit dynamics on the GPU.

Biomech Model Mechanobiol 2019 Jun 12;18(3):681-700. Epub 2019 Jan 12.

Department of Obstetrics and Gynaecology, Norfolk and Norwich University Hospital NHS Trust, Norwich, UK.

During physiological or 'natural' childbirth, the fetal head follows a distinct motion pattern-often referred to as the cardinal movements or 'mechanisms' of childbirth-due to the biomechanical interaction between the fetus and maternal pelvic anatomy. The research presented in this paper introduces a virtual reality-based simulation of physiological childbirth. The underpinning science is based on two numerical algorithms including the total Lagrangian explicit dynamics method to calculate soft tissue deformation and the partial Dirichlet-Neumann contact method to calculate the mechanical contact interaction between the fetal head and maternal pelvic anatomy. The paper describes the underlying mathematics and algorithms of the solution and their combination into a computer-based implementation. The experimental section covers first a number of validation experiments on simple contact mechanical problems which is followed by the main experiment of running a virtual reality childbirth. Realistic mesh models of the fetus, bony pelvis and pelvic floor muscles were subjected to the intra-uterine expulsion forces which aim to propel the virtual fetus through the virtual birth canal. Following a series of simulations, taking variations in the shape and size of the geometric models into account, we consistently observed the cardinal movements in the simulator just as they happen in physiological childbirth. The results confirm the potential of the simulator as a predictive tool for problematic childbirths subject to patient-specific adaptations.
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http://dx.doi.org/10.1007/s10237-018-01109-xDOI Listing
June 2019

Mode of delivery following an OASIS and caesarean section rates.

Eur J Obstet Gynecol Reprod Biol 2018 Nov 13;230:28-31. Epub 2018 Sep 13.

Norfolk and Norwich University Hospital, United Kingdom.

Objectives: While the rate of obstetric anal sphincter injury (OASIS) is increasing, there is a lack of evidence on how best to advise women on mode of delivery (MOD) afterwards. The objectives of this study were to assess the clinical value of bowel symptoms, endoanal ultrasound and anorectal manometry in the management of pregnancies after an OASIS and evaluate the performance of different algorithms.

Study Design: This was a retrospective analysis of prospectively collected data in a university hospital perineal clinic. Women with OASIS undergoing endoanal ultrasound scan (EAUS) and anorectal manometry (AM) were included in this study (all women with an OASIS, except the asymptomatic 3a tears). A number of published algorithms were theoretically applied in this cohort to define recommended MOD after an OASIS.

Results: Out of the 233 women included in the study, 51 (21.9%) were symptomatic, 141 (60.5%) had persistent sphincter defects on EAUS and 124 (53.2%) had abnormal AM. One asymptomatic and five symptomatic women were found to have isolated internal anal sphincter (IAS) defects without external anal sphincter (EAS) defects. There were no women with low resting pressure and normal incremental squeeze pressure. The application of the algorithm requiring only one abnormal investigation to be recommended caesarean would have led to an 81.5% caesarean rate. If women with symptoms of anal incontinence or abnormal investigations would be advised for caesarean the rate would be 85.0%. Using the local protocol where symptomatic women only needed one of the two investigations to be abnormal but asymptomatic women were required to have both investigations being abnormal, 94 were considered for caesarean (40.3%).

Conclusion: There is a wide range in the number of patients recommended to have caesarean section after an OASIS, depending on the used criteria and management algorithms. There is minimal additional information gained from identifying internal anal sphincter defects and measuring low resting pressures at manometry.
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http://dx.doi.org/10.1016/j.ejogrb.2018.09.020DOI Listing
November 2018

Neurokinin 3 receptor antagonism - Is this the end of HRT?

Post Reprod Health 2018 06;24(2):61-62

Editors, Post Reproductive Health.

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http://dx.doi.org/10.1177/2053369118780657DOI Listing
June 2018

A note on a precursor of behavioral momentum.

J Exp Anal Behav 2018 01;109(1):66-69

The Lovaas Institute, Minneapolis, MN.

This is a historical note on a precursor of the concept of behavioral momentum in the late 1950s and early 1960s, in particular, Charles B. description of it in terms of behavioral durability. The note is based largely on two email exchanges we had with John A. (Tony) Nevin, who offered insights on behavioral momentum as a term and a concept that are fit to be public on the occasion of this issue of the Journal of the Experimental Analysis of Behavior in his honor. Nevin addressed graduate work at Columbia University, the Newtonian analogy, the term behavioral momentum, and precursors of his work that are now lost in history. Ferster's description, though, was more compellingly modern than the others and the one first based in research on human operant behavior.
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http://dx.doi.org/10.1002/jeab.301DOI Listing
January 2018