• Landslides in the Upper Submarine Slopes of Volcanic Islands: The Central Azores

      Chang, Yu‐Chun; orcid: 0000-0003-4941-5437; email: yu-chun.chang@manchester.ac.uk; Mitchell, Neil C.; orcid: 0000-0002-6483-2450; Quartau, Rui; orcid: 0000-0003-3148-7520 (2021-09-28)
      Abstract: Small landslides in the upper submarine slopes of volcanic islands present potential hazards locally because of their high frequency. We examine evidence for landsliding in high‐resolution bathymetric data from Faial, Pico, São Jorge, and Terceira islands of the Azores. Because the rugged morphology of the upper slopes makes landslides difficult to interpret, we develop two classification schemes for the 1,227 identified slope valleys. One scheme addresses how recognizable the valleys were as originating from landslides (whether scarps are prominent or indefinite), whereas the other scheme addresses valley types (whether apparently produced by single or multiple failures). Size distributions are used to assess the relative occurrence of large versus small landslides. Thirteen landslides are predicted to have generated tsunami heights at source of >1 m and one with height of >7 m. Some slopes have gradients far above 30°, the angle of repose of incohesive clastic sediment, so the seabed in those areas is strengthened perhaps by carbonate cementation, by seismic shaking or by the presence of coherent lava or lava talus. Using all types of slope valleys, Faial and Pico have smaller affected volumes per unit slope area than those of São Jorge and Terceira. These differences could be associated with varied seismic activity, with more frequent earthquakes beneath Faial and Pico preventing the build‐up of sediments on their slopes. Submarine landslide statistics are therefore potentially useful for assessing long‐term earthquake hazards of volcanic islands in seismically active environments such as the Azores.
    • We See Data Everywhere Except in the Productivity Statistics

      Goodridge, Peter; email: peter.goodridge@manchester.ac.uk; Haskel, Jonathan; Edquist, Harald (2021-09-28)
      This paper uses Labor Force Survey data for European countries to estimate national investment in data assets, where the asset boundary is extended beyond that for software and databases as currently defined in the System of National Accounts. We find that: (a) in 2011–2018, 1.4 percent of EU‐28 employment was engaged in the formation of (software and) data assets, with a mean growth rate of 5 percent per annum; (b) on average in 2011–2016, expanding the asset boundary raises the level of own‐account GFCF in software and databases in the EU‐16 by 61 percent, and mean growth in real investment in own‐account software and data assets to 6.9 percent pa, compared to 2.7 percent pa in national accounts; (c) in 2011–2016, expansion of the asset boundary raises labor productivity growth in the EU‐13 from 0.79 percent to 0.83 percent pa, and the contribution of software and data capital deepening over three‐fold, from 0.03 percent to 0.10 percent pa.
    • Methods for quantifying methane emissions using unmanned aerial vehicles: a review

      Shaw, Jacob T.; orcid: 0000-0003-3558-3894; email: jacob.shaw@manchester.ac.uk; Shah, Adil; orcid: 0000-0002-5692-3715; Yong, Han; Allen, Grant; orcid: 0000-0002-7070-3620; email: grant.allen@manchester.ac.uk (The Royal Society, 2021-09-27)
      Methane is an important greenhouse gas, emissions of which have vital consequences for global climate change. Understanding and quantifying the sources (and sinks) of atmospheric methane is integral for climate change mitigation and emission reduction strategies, such as those outlined in the 2015 UN Paris Agreement on Climate Change. There are ongoing international efforts to constrain the global methane budget, using a wide variety of measurement platforms across a range of spatial and temporal scales. The advancements in unmanned aerial vehicle (UAV) technology over the past decade have opened up a new avenue for methane emission quantification. UAVs can be uniquely equipped to monitor natural and anthropogenic emissions at local scales, displaying clear advantages in versatility and manoeuvrability relative to other platforms. Their use is not without challenge, however: further miniaturization of high-performance methane instrumentation is needed to fully use the benefits UAVs afford. Developments in the models used to simulate atmospheric transport and dispersion across small, local scales are also crucial to improved flux accuracy and precision. This paper aims to provide an overview of currently available UAV-based technologies and sampling methodologies which can be used to quantify methane emission fluxes at local scales. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.
    • Cortical Visual Impairment in Childhood: ‘Blindsight’ and the Sprague Effect Revisited

      Leisman, Gerry; orcid: 0000-0002-9975-7331; email: g.leisman@alumni.manchester.ac.uk; Machado, Calixto; orcid: 0000-0002-0539-5844; email: braind@infomed.sld.cu; Melillo, Robert; email: drrm1019@aol.com (MDPI, 2021-09-27)
      The paper discusses and provides support for diverse processes of brain plasticity in visual function after damage in infancy and childhood in comparison with injury that occurs in the adult brain. We provide support and description of neuroplastic mechanisms in childhood that do not seemingly exist in the same way in the adult brain. Examples include the ability to foster the development of thalamocortical connectivities that can circumvent the lesion and reach their cortical destination in the occipital cortex as the developing brain is more efficient in building new connections. Supporting this claim is the fact that in those with central visual field defects we can note that the extrastriatal visual connectivities are greater when a lesion occurs earlier in life as opposed to in the neurologically mature adult. The result is a significantly more optimized system of visual and spatial exploration within the ‘blind’ field of view. The discussion is provided within the context of “blindsight” and the “Sprague Effect”.
    • Seasonal patterns of malaria, genital infection, nutritional and iron status in non-pregnant and pregnant adolescents in Burkina Faso: a secondary analysis of trial data

      Roberts, Stephen A.; orcid: 0000-0002-7477-7731; Brabin, Loretta; orcid: 0000-0003-4478-6503; email: loretta.brabin@manchester.ac.uk; Tinto, Halidou; orcid: 0000-0002-0472-3586; Gies, Sabine; Diallo, Salou; orcid: 0000-0002-1253-4726; Brabin, Bernard; orcid: 0000-0001-6860-2508 (BioMed Central, 2021-09-27)
      Abstract: Background: Adolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions. Methods: Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS (< 0 mg/kg). Continuous outcomes were fitted to a mixed-effects linear model with month, age and pregnancy status as fixed effect covariates and woman as a random effect. Dichotomous infection outcomes were fitted with analogous logistic regression models. Results: Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P < 0.001), peaking at 81% in those who became pregnant. Seasonal variation occurred in antibiotic prescription rates (0.7–1.8 prescriptions/100 weekly visits, P < 0.001) and chorioamnionitis prevalence (range 15–68%, P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2–22 μg/ml, P < 0.016), when chorioamnionitis was least frequent. BIS fluctuated annually by up to 53.2% per year around the mean BIS (5.1 mg/kg2, range 4.1–6.8 mg/kg), with low BIS (< 0 mg/kg) of 8.7% in the dry and 9.8% in the wet seasons (P = 0.36). Median serum transferrin receptor increased during the wet season (P < 0.001). Higher hepcidin concentration in the wet season corresponded with rising malaria prevalence and use of prescriptions, but with no change in BIS. Mean Body Mass Index and Mid-Upper-Arm-Circumference values peaked mid-dry season (both P < 0.001). Conclusions: Our analysis supports preventive treatment of malaria among adolescents 15–19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated.
    • Fanconi Anaemia, Childhood Cancer and the BRCA Genes

      Woodward, Emma R.; orcid: 0000-0002-6297-2855; email: stefan.meyer@manchester.ac.uk; Meyer, Stefan; orcid: 0000-0002-2283-3690; email: emma.woodward@mft.nhs.uk (MDPI, 2021-09-27)
      Fanconi anaemia (FA) is an inherited chromosomal instability disorder characterised by congenital and developmental abnormalities and a strong cancer predisposition. In less than 5% of cases FA can be caused by bi-allelic pathogenic variants (PGVs) in BRCA2/FANCD1 and in very rare cases by bi-allelic PGVs in BRCA1/FANCS. The rarity of FA-like presentation due to PGVs in BRCA2 and even more due to PGVs in BRCA1 supports a fundamental role of the encoded proteins for normal development and prevention of malignant transformation. While FA caused by BRCA1/2 PGVs is strongly associated with distinct spectra of embryonal childhood cancers and AML with BRCA2-PGVs, and also early epithelial cancers with BRCA1 PGVs, germline variants in the BRCA1/2 genes have also been identified in non-FA childhood malignancies, and thereby implying the possibility of a role of BRCA PGVs also for non-syndromic cancer predisposition in children. We provide a concise review of aspects of the clinical and genetic features of BRCA1/2-associated FA with a focus on associated malignancies, and review novel aspects of the role of germline BRCA2 and BRCA1 PGVs occurring in non-FA childhood cancer and discuss aspects of clinical and biological implications.
    • Uncertainty, Anxiety and Isolation: Experiencing the COVID-19 Pandemic and Lockdown as a Woman with Polycystic Ovary Syndrome (PCOS)

      Atkinson, Lou; email: l.atkinson1@aston.ac.uk; Kite, Chris; orcid: 0000-0003-1342-274X; email: c.kite@chester.ac.uk; McGregor, Gordon; orcid: 0000-0001-8963-9107; email: ac4378@coventry.ac.uk; James, Tamsin; email: jamestno@aston.ac.uk; Clark, Cain C. T.; orcid: 0000-0002-6610-4617; email: ad0183@coventry.ac.uk; Randeva, Harpal S.; email: harpal.randeva@uhcw.nhs.uk; Kyrou, Ioannis; email: ad6702@coventry.ac.uk (MDPI, 2021-09-25)
      Background: The COVID-19 pandemic and the related lockdown measures presented a significant risk to physical and mental wellbeing in affected populations. Women with polycystic ovary syndrome (PCOS) are predisposed to several cardio-metabolic risk factors which increase the susceptibility to severe COVID-19 and also exhibit increased likelihood of impaired mental health wellbeing. Therefore, these women who usually receive care from multiple primary and specialist healthcare services may be disproportionately impacted by this pandemic and the related restrictions. This study aimed to explore the lived experience of the first UK national lockdown as a woman with PCOS. Methods: As part of a larger cross-sectional study, 12 women with PCOS living in the UK during the first national COVID-19 lockdown were recruited to a qualitative study. Telephone interviews were conducted in June/July of 2020, and data collected were subjected to thematic analysis. Results: Five themes were identified. “My PCOS Journey” describes participants’ experiences of diagnosis, treatment and ongoing management of their PCOS. “Living Through Lockdown” describes the overall experience and impact of the lockdown on all aspects of participants’ lives. “Self-care and Managing Symptoms” describe multiple challenges to living well with PCOS during the lockdown, including lack of access to supplies and services, and disruption to weight management. “Healthcare on Hold” describes the uncertainty and anxiety associated with delays in accessing specialised healthcare for a range of PCOS aspects, including fertility treatment. “Exacerbating Existing Issues” captures the worsening of pre-existing mental health issues, and an increase in health anxiety and feelings of isolation. Conclusion: For the women with PCOS in this study, the COVID-19 pandemic and the first national lockdown was mostly experienced as adding to the pre-existing challenges of living with their condition. The mental health impact experienced by the study participants was increased due to lack of access to their normal support strategies, limitations on healthcare services and uncertainty about their risk of COVID-19.
    • A Novel Ship Collision Avoidance Awareness Approach for Cooperating Ships Using Multi-Agent Deep Reinforcement Learning

      Chen, Chen; orcid: 0000-0003-1064-4961; email: chenchen0120@wit.edu.cn; Ma, Feng; orcid: 0000-0002-1357-3006; email: martin7wind@whut.edu.cn; Xu, Xiaobin; email: xuxiaobin1980@hdu.edu.cn; Chen, Yuwang; orcid: 0000-0002-2007-1821; email: Yu-wang.Chen@manchester.ac.uk; Wang, Jin; email: J.Wang@ljmu.ac.uk (MDPI, 2021-09-25)
      Ships are special machineries with large inertias and relatively weak driving forces. Simulating the manual operations of manipulating ships with artificial intelligence (AI) and machine learning techniques becomes more and more common, in which avoiding collisions in crowded waters may be the most challenging task. This research proposes a cooperative collision avoidance approach for multiple ships using a multi-agent deep reinforcement learning (MADRL) algorithm. Specifically, each ship is modeled as an individual agent, controlled by a Deep Q-Network (DQN) method and described by a dedicated ship motion model. Each agent observes the state of itself and other ships as well as the surrounding environment. Then, agents analyze the navigation situation and make motion decisions accordingly. In particular, specific reward function schemas are designed to simulate the degree of cooperation among agents. According to the International Regulations for Preventing Collisions at Sea (COLREGs), three typical scenarios of simulation, which are head-on, overtaking and crossing, are established to validate the proposed approach. With sufficient training of MADRL, the ship agents were capable of avoiding collisions through cooperation in narrow crowded waters. This method provides new insights for bionic modeling of ship operations, which is of important theoretical and practical significance.
    • Exceptional uranium(VI)-nitride triple bond covalency from 15 N nuclear magnetic resonance spectroscopy and quantum chemical analysis

      Du, Jingzhen; orcid: 0000-0003-4037-9281; Seed, John A.; orcid: 0000-0002-3751-0325; Berryman, Victoria E. J.; Kaltsoyannis, Nikolas; Adams, Ralph W.; orcid: 0000-0001-8009-5334; email: ralph.adams@manchester.ac.uk; Lee, Daniel; orcid: 0000-0002-1015-0980; email: daniel.lee@manchester.ac.uk; Liddle, Stephen T.; orcid: 0000-0001-9911-8778; email: steve.liddle@manchester.ac.uk (Nature Publishing Group UK, 2021-09-24)
      Abstract: Determining the nature and extent of covalency of early actinide chemical bonding is a fundamentally important challenge. Recently, X-ray absorption, electron paramagnetic, and nuclear magnetic resonance spectroscopic studies have probed actinide-ligand covalency, largely confirming the paradigm of early actinide bonding varying from ionic to polarised-covalent, with this range sitting on the continuum between ionic lanthanide and more covalent d transition metal analogues. Here, we report measurement of the covalency of a terminal uranium(VI)-nitride by 15N nuclear magnetic resonance spectroscopy, and find an exceptional nitride chemical shift and chemical shift anisotropy. This redefines the 15N nuclear magnetic resonance spectroscopy parameter space, and experimentally confirms a prior computational prediction that the uranium(VI)-nitride triple bond is not only highly covalent, but, more so than d transition metal analogues. These results enable construction of general, predictive metal-ligand 15N chemical shift-bond order correlations, and reframe our understanding of actinide chemical bonding to guide future studies.
    • Capturing convection essential for projections of climate change in African dust emission

      Garcia-Carreras, Luis; orcid: 0000-0002-9844-3170; email: luis.garcia-carreras@manchester.ac.uk; Marsham, John H.; orcid: 0000-0003-3219-8472; Stratton, Rachel A.; Tucker, Simon (Nature Publishing Group UK, 2021-09-24)
      Abstract: The summertime Sahara and Sahel are the world’s largest source of airborne mineral dust. Cold-pool outflows from moist convection (‘haboobs’) are a dominant source of summertime uplift but are essentially missing in global models, raising major questions on the reliability of climate projections of dust and dust impacts. Here we use convection-permitting simulations of pan-African climate change, which explicitly capture haboobs, to investigate whether this key limitation of global models affects projections. We show that explicit convection is key to capturing the observed summertime maximum of dust-generating winds, which is missed with parameterised convection. Despite this, future climate changes in dust-generating winds are more sensitive to the effects of explicit convection on the wider meteorology than they are to the haboobs themselves, with model differences in the change in dust-generating winds reaching 60% of current values. The results therefore show the importance of improving convection in climate models for dust projections.
    • Magneto-hydrodynamics of multi-phase flows in heterogeneous systems with large property gradients

      Flint, T. F.; email: thomas.flint@manchester.ac.uk; Smith, M. C.; Shanthraj, P. (Nature Publishing Group UK, 2021-09-23)
      Abstract: The complex interplay between thermal, hydrodynamic, and electromagnetic, forces governs the evolution of multi-phase systems in high technology applications, such as advanced manufacturing and fusion power plant operation. In this work, a new formulation of the time dependent magnetic induction equation is fully coupled to a set of conservation laws for multi-phase fluid flow, energy transport and chemical species transport that describes melting and solidification state transitions. A finite-volume discretisation of the resulting system of equations is performed, where a novel projection method is formulated to ensure that the magnetic field remains divergence free. The proposed framework is validated by accurately replicating a Hartmann flow profile. Further validation is performed through correctly predicting the experimentally observed trajectory of Argon bubbles rising in a liquid metal under varying applied magnetic fields. Finally, the applicability of the framework to technologically relevant processes is illustrated through the simulation of an electrical arc welding process between dissimilar metals. The proposed framework addresses an urgent need for numerical methods to understand the evolution of multi-phase systems with large electromagnetic property contrast.
    • Can we achieve better recruitment by providing better information? Meta-analysis of ‘studies within a trial’ (SWATs) of optimised participant information sheets

      Madurasinghe, Vichithranie W.; Bower, Peter; orcid: 0000-0001-9558-3349; email: peter.bower@manchester.ac.uk; Eldridge, Sandra; Collier, David; Graffy, Jonathan; Treweek, Shaun; Knapp, Peter; Parker, Adwoa; Rick, Jo; Salisbury, Chris; et al. (BioMed Central, 2021-09-23)
      Abstract: Background: The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded ‘studies within a trial’ (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment. Methods: Seven ‘host’ trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part. Results: Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I2 = 0%). Conclusions: Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies. Trial registration: Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133)
    • Collaborative management of the Grand Ethiopian Renaissance Dam increases economic benefits and resilience

      Basheer, Mohammed; orcid: 0000-0001-9468-2249; Nechifor, Victor; orcid: 0000-0001-8034-4070; Calzadilla, Alvaro; orcid: 0000-0001-8424-8473; Siddig, Khalid; orcid: 0000-0003-1339-4507; Etichia, Mikiyas; Whittington, Dale; Hulme, David; Harou, Julien J.; email: julien.harou@manchester.ac.uk (Nature Publishing Group UK, 2021-09-23)
      Abstract: The landscape of water infrastructure in the Nile Basin is changing with the construction of the Grand Ethiopian Renaissance Dam. Although this dam could improve electricity supply in Ethiopia and its neighbors, there is a lack of consensus between Ethiopia, Sudan, and Egypt on the dam operation. We introduce a new modeling framework that simulates the Nile River System and Egypt’s macroeconomy, with dynamic feedbacks between the river system and the macroeconomy. Because the two systems “coevolve” throughout multi-year simulations, we term this a “coevolutionary” modeling framework. The framework is used to demonstrate that a coordinated operating strategy could allow the Grand Ethiopian Renaissance Dam to help meet water demands in Egypt during periods of water scarcity and increase hydropower generation and storage in Ethiopia during high flows. Here we show the hydrological and macroeconomic performance of this coordinated strategy compared to a strategy that resembles a recent draft proposal for the operation of the dam discussed in Washington DC.
    • Adaptive Impedance-Conditioned Phase-Locked Loop for the VSC Converter Connected to Weak Grid

      Hamood, Mostafa A.; email: mostafa.hamood@manchester.ac.uk; Marjanovic, Ognjen; email: Ognjen.Marjanovic@manchester.ac.uk; Carrasco, Joaquin; email: joaquin.carrascogomez@manchester.ac.uk (MDPI, 2021-09-23)
      In this paper, an adaptive version of the impedance-conditioned phase-locked loop (IC-PLL), namely the adaptive IC-PLL (AIC-PLL), is proposed. The IC-PLL has recently been proposed to address the issue of synchronisation with a weak AC grid by supplementing the conventional synchronous reference frame phase-locked loop (SRF-PLL) with an additional virtual impedance term. The resulting IC-PLL aims to synchronise the converter to a remote and stronger point in the grid, hence increasing the upper bound on the achievable power transfer achieved by the VSC converter connected to the weak grid. However, the issue of the variable grid strength imposes another challenge in the operation of the IC-PLL. This is because the IC-PLL requires impedance estimation methods to estimate the value of the virtual impedance part. In AIC-PLL, the virtual impedance part is estimated by appending another dynamic loop in the exciting IC-PLL. In this method, an additional closed loop is involved so that the values of the virtual inductance and resistance are internally estimated and adapted. Hence, the VSC converter becomes effectively viable for the case of the grid strength variable, where the estimation of the grid impedance becomes unnecessary. The results show that the converter that relies on AIC-PLL has the ability to transfer power that is approximately equal to the theoretical maximum power while maintaining satisfactory dynamic performance.
    • 18 Years of Medication-Related Osteonecrosis of the Jaw (MRONJ) Research: Where Are We Now?—An Umbrella Review

      Sacco, Roberto; orcid: 0000-0002-8413-1053; email: roberto.sacco@manchester.ac.uk; Calasans-Maia, Monica Diuana; orcid: 0000-0001-5759-7926; email: monicacalasansmaia@gmail.com; Woolley, Julian; orcid: 0000-0001-7879-8815; email: julianwoolley@gmail.com; Akintola, Oladapo; email: dapoakintola@nhs.net; de Almeida Barros Mourão, Carlos Fernando; orcid: 0000-0001-5775-0222; email: mouraocf@gmail.com; Moraschini, Vittorio; email: vitt.mf@gmail.com; Kushnerev, Evgeny; email: evgeny.kushnerev@manchester.ac.uk; Acocella, Alessandro; email: alessandroacocella@yahoo.it; Obisesan, Olamide; email: oobisesan@nhs.net; Yates, Julian; email: julian.yates@manchester.ac.uk (MDPI, 2021-09-23)
      Background: Osteonecrosis of the jaw (ONJ) is a condition affecting patients exposed to medications used to treat benign and malignant conditions of bone tissue. Many studies have highlighted that ONJ is a severe condition, which is very challenging to manage, especially in individuals with oncologic disease. The aim of this umbrella review is to analyze all available interventional and non-interventional systematic reviews published on medication-related osteonecrosis of the jaw (MRONJ) and summarize this evidence. Material and methods: A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until June 2021. An additional manual search was also performed in systematic review registries (PROSPERO, INPLASY, JBI and OFS) to identify possible missing reviews. Data were extracted from relevant papers and analyzed according to the outcomes selected in this review. Results: The search generated 25 systematic reviews eligible for the analysis. The total number of patients included in the analysis was 80,840. Of the reviews, 64% (n = 16) were non-interventional and 36% (n = 9) were interventional. Study designs included case series 20.50% (n = 140), retrospective cohort studies 12.30% (n = 84) and case reports 12.20% (n = 83). It was unclear what study design was used for 277 studies included in the 25 systematic reviews. Conclusions: The data reviewed confirmed that the knowledge underpinning MRONJ in the last 20 years is still based on weak evidence. This umbrella review highlighted a widespread low-level quality of studies and many poorly designed reviews.
    • HE4 as a Biomarker for Endometrial Cancer

      Behrouzi, Roya; email: rbehrouzi@doctors.org.uk; Barr, Chloe E.; email: Chloe.Barr@mft.nhs.uk; Crosbie, Emma J.; orcid: 0000-0003-0284-8630; email: Emma.Crosbie@manchester.ac.uk (MDPI, 2021-09-23)
      There are currently no blood biomarkers in routine clinical use in endometrial carcinoma (EC). Human epididymis protein 4 (HE4) is a glycoprotein that is overexpressed in the serum of patients with EC, making it a good candidate for use as a diagnostic and/or prognostic biomarker. HE4 is correlated with poor prognostic factors, including stage, myometrial invasion and lymph node metastases, which means it could be used to guide decisions regarding the extent of surgery and need for adjuvant therapy. Serum HE4 has also shown promise for predicting responses to progestin therapy in early-stage EC. The use of algorithms and indices incorporating serum HE4 and other biomarkers, including clinical and imaging variables, is an area of increasing interest. Serum HE4 levels rise with age and renal dysfunction, which may affect the interpretation of results. This review covers the evidence supporting the use of HE4 as an EC biomarker for diagnosis, prognosis, recurrence monitoring, and prediction of therapy response. The evidence for combining serum HE4 with other biomarkers, including clinical and imaging variables, its value as a biomarker in other biofluids and potential challenges of its clinical use are also discussed.
    • The prognostic value of emergency department measured hypertension: A systematic review and meta‐analysis

      Reynard, Charles; orcid: 0000-0002-7534-2668; email: Charles.reynard@postgrad.manchester.ac.uk; van den Berg, Patricia; orcid: 0000-0001-8148-1130; Oliver, Govind; orcid: 0000-0001-6051-6090; Naguib, Mina Peter; Sammut‐Powell, Camilla; McMillan, Brian; orcid: 0000-0002-0683-3877; Heagerty, Anthony; orcid: 0000-0002-9043-2119; Body, Richard; orcid: 0000-0001-9089-8130 (2021-09-22)
      Abstract: Objectives: The objective was to assess the prognostic value of hypertension detected in the emergency department (ED). Methods: The ED presents a unique opportunity to predict long‐term cardiovascular disease (CVD) outcomes with its potential for high‐footfall, and large‐scale routine data collection applied to underserved patient populations. A systematic review and meta‐analyses were conducted to assess the prognostic performance and feasibility of ED‐measured hypertension as a risk factor for long‐term CVD outcomes. We searched MEDLINE and Embase databases and gray literature sources. The target populations were undifferentiated ED patients. The prognostic factor of interest was hypertension. Feasibility outcomes included prevalence, reliability, and follow‐up attendance. Meta‐analyses were performed for feasibility using a random effect and exact likelihood. Results: The searches identified 1072 studies after title and abstract review, 53 studies had their full text assessed for eligibility, and 26 studies were included. Significant heterogeneity was identified, likely due to the international populations and differing study design. The meta‐analyses estimate of prevalence for ED‐measured hypertension was 0.31 (95% confidence interval 0.25–0.37). ED hypertension was persistent outside the ED (FE estimate of 0.50). The proportion of patients attending follow‐up was low with an exact likelihood estimate of 0.41. Three studies examined the prognostic performance of hypertension and demonstrated an increased risk of long‐term CVD outcomes. Conclusion: Hypertension can be measured feasibly in the ED and consequently used in a long‐term cardiovascular risk prediction model. There is an opportunity to intervene in targeted individuals, using routinely collected data.
    • Scalability of resonant motor-driven flapping wing propulsion systems

      Nabawy, Mostafa R. A.; orcid: 0000-0002-4252-1635; email: mostafa.ahmednabawy@manchester.ac.uk; Marcinkeviciute, Ruta (The Royal Society, 2021-09-22)
      This work aims to develop an integrated conceptual design process to assess the scalability and performance of propulsion systems of resonant motor-driven flapping wing vehicles. The developed process allows designers to explore the interaction between electrical, mechanical and aerodynamic domains in a single transparent design environment. Wings are modelled based on a quasi-steady treatment that evaluates aerodynamics from geometry and kinematic information. System mechanics is modelled as a damped second-order dynamic system operating at resonance with nonlinear aerodynamic damping. Motors are modelled using standard equations that relate operational parameters and AC voltage input. Design scaling laws are developed using available data based on current levels of technology. The design method provides insights into the effects of changing core design variables such as the actuator size, actuator mass fraction and pitching kinematics on the overall design solution. It is shown that system efficiency achieves peak values of 30–36% at motor masses of 0.5–1 g when a constant angle of attack kinematics is employed. While sinusoidal angle of attack kinematics demands more aerodynamic and electric powers compared with the constant angle of attack case, sinusoidal angle of attack kinematics can lead to a maximum difference of around 15% in peak system efficiency.
    • Endothelium-Derived Hyperpolarizing Factor (EDHF) Mediates Acetylsalicylic Acid (Aspirin) Vasodilation of Pregnant Rat Mesenteric Arteries

      Helgadóttir, Helga; email: helgadottir@hi.is; Tropea, Teresa; email: teresa.tropea@manchester.ac.uk; Gizurarson, Sveinbjörn; orcid: 0000-0001-7824-9752; email: sveinbj@hi.is; Mandalà, Maurizio; orcid: 0000-0003-3736-0205; email: m.mandala@unical.it (MDPI, 2021-09-21)
      Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10−12–10−6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10−4 M); (b) cyclooxygenase (Indomethacin, 10−5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10−7 M), intermediate conductance (IKca, TRAM34, 10−5 M), and big conductance (BKca, paxilline, 10−5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.
    • Restoring fertility in yeast hybrids: Breeding and quantitative genetics of beneficial traits.

      Naseeb, Samina; orcid: 0000-0003-3599-5813; Visinoni, Federico; orcid: 0000-0001-9840-7017; Hu, Yue; Hinks Roberts, Alex J; Maslowska, Agnieszka; Walsh, Thomas; Smart, Katherine A; Louis, Edward J; orcid: 0000-0003-1157-3608; Delneri, Daniela; orcid: 0000-0001-8070-411X (2021-09-21)
      Hybrids between species can harbor a combination of beneficial traits from each parent and may exhibit hybrid vigor, more readily adapting to new harsher environments. Interspecies hybrids are also sterile and therefore an evolutionary dead end unless fertility is restored, usually via auto-polyploidisation events. In the genus, hybrids are readily found in nature and in industrial settings, where they have adapted to severe fermentative conditions. Due to their hybrid sterility, the development of new commercial yeast strains has so far been primarily conducted via selection methods rather than via further breeding. In this study, we overcame infertility by creating tetraploid intermediates of interspecies hybrids to allow continuous multigenerational breeding. We incorporated nuclear and mitochondrial genetic diversity within each parental species, allowing for quantitative genetic analysis of traits exhibited by the hybrids and for nuclear-mitochondrial interactions to be assessed. Using pooled F12 generation segregants of different hybrids with extreme phenotype distributions, we identified quantitative trait loci (QTLs) for tolerance to high and low temperatures, high sugar concentration, high ethanol concentration, and acetic acid levels. We identified QTLs that are species specific, that are shared between species, as well as hybrid specific, in which the variants do not exhibit phenotypic differences in the original parental species. Moreover, we could distinguish between mitochondria-type-dependent and -independent traits. This study tackles the complexity of the genetic interactions and traits in hybrid species, bringing hybrids into the realm of full genetic analysis of diploid species, and paves the road for the biotechnological exploitation of yeast biodiversity. [Abstract copyright: Copyright © 2021 the Author(s). Published by PNAS.]