• A Cross-Sectional Study Investigating the Relationship Between Alexithymia and Suicide, Violence, and Dual Harm in Male Prisoners

      Hemming, Laura; Shaw, Jennifer; Haddock, Gillian; Carter, Lesley-Anne; Pratt, Daniel; email: daniel.pratt@manchester.ac.uk (Frontiers Media S.A., 2021-04-29)
      Background: Suicide and violence are common within male prisoners. One suggested risk factor for both behaviors is alexithymia. Alexithymia describes a deficit in identifying and describing feelings and is also related to externally oriented thinking. This study aimed to explore the relationship between alexithymia, suicide, violence and dual harm in male prisoners. Methods: Eighty male prisoners were recruited from three prisons. Participants were asked to complete a battery of questionnaires including measures of alexithymia (TAS-20), suicide ideation (ASIQ), suicide behavior, violence ideation (SIV), violence behavior, depression (BDI-II), hopelessness (BHS), impulsivity (DII) and anger (NAS-PI). Regression analyses and ANOVAS were conducted to assess the association between alexithymia (and its subcomponents) with six outcomes; suicide ideation, suicide behavior, violence ideation, violence behavior, dual harm ideation and dual harm behavior. Results: Alexithymia was a univariate predictor of suicide ideation, though was not a significant predictor when considered in a multivariate model. Alexithymia was a significant multivariate predictor of suicide behavior. Alexithymia was not a significant multivariate predictor of violence ideation or behavior. There were no significant differences in alexithymia or subscales between those with suicide ideation/behavior alone, violence ideation/behavior alone and those with dual harm ideation/behavior. Conclusion: In male prisoners, alexithymia appears an important univariate predictor of suicide and violence, though the current study suggests no significant contribution above other well-known correlates of suicide and violence.
    • A Novel Mechanism of Ataxia Telangiectasia Mutated Mediated Regulation of Chromatin Remodeling in Hypoxic Conditions

      Likhatcheva, Maria; Gieling, Roben G.; Brown, James A. L.; Demonacos, Constantinos; Williams, Kaye J.; email: kaye.williams@manchester.ac.uk (Frontiers Media S.A., 2021-09-21)
      The effects of genotoxic stress can be mediated by activation of the Ataxia Telangiectasia Mutated (ATM) kinase, under both DNA damage-dependent (including ionizing radiation), and independent (including hypoxic stress) conditions. ATM activation is complex, and primarily mediated by the lysine acetyltransferase Tip60. Epigenetic changes can regulate this Tip60-dependent activation of ATM, requiring the interaction of Tip60 with tri-methylated histone 3 lysine 9 (H3K9me3). Under hypoxic stress, the role of Tip60 in DNA damage-independent ATM activation is unknown. However, epigenetic changes dependent on the methyltransferase Suv39H1, which generates H3K9me3, have been implicated. Our results demonstrate severe hypoxic stress (0.1% oxygen) caused ATM auto-phosphorylation and activation (pS1981), H3K9me3, and elevated both Suv39H1 and Tip60 protein levels in FTC133 and HCT116 cell lines. Exploring the mechanism of ATM activation under these hypoxic conditions, siRNA-mediated Suv39H1 depletion prevented H3K9me3 induction, and Tip60 inhibition (by TH1834) blocked ATM auto-phosphorylation. While MDM2 (Mouse double minute 2) can target Suv39H1 for degradation, it can be blocked by sirtuin-1 (Sirt1). Under severe hypoxia MDM2 protein levels were unchanged, and Sirt1 levels depleted. SiRNA-mediated depletion of MDM2 revealed MDM2 dependent regulation of Suv39H1 protein stability under these conditions. We describe a novel molecular circuit regulating the heterochromatic state (H3K9me3 positive) under severe hypoxic conditions, showing that severe hypoxia-induced ATM activation maintains H3K9me3 levels by downregulating MDM2 and preventing MDM2-mediated degradation of Suv39H1. This novel mechanism is a potential anti-cancer therapeutic opportunity, which if exploited could target the hypoxic tumor cells known to drive both tumor progression and treatment resistance.
    • A Subtle Profile With a Significant Impact: Language and Communication Difficulties for Autistic Females Without Intellectual Disability

      Sturrock, Alexandra; email: Alexandra.sturrock@manchester.ac.uk; Adams, Catherine; Freed, Jenny (Frontiers Media S.A., 2021-08-09)
      The presentation of autism in females is poorly understood, which is thought to contribute to missed or later- age diagnosis, especially for those without intellectual disability. Dedicated research into social and behavioral differences has indicated a specific female phenotype of autism. However, less has been done to explore language and communication profiles, despite known sex/gender differences in typically developing populations. This article provides a synthesis of recent work from this small but emerging field. It focuses on a series of four preliminary and explorative studies conducted by the authors and embeds this within the wider literature. Findings suggest a specific profile of language and communication strengths and weaknesses for autistic females without intellectual disability (compared to autistic males and typically developing females). Furthermore, despite the relatively subtle presentation of difficulties (compared to autistic males), the impact on functionality, social inter-relations and emotional well-being, appears to be equitable and significant. The discussion highlights the need for further empirical research and proposes areas for investigation. Implications for clinical practice include the need for better recognition, testing and provision of interventions dedicated to the language and communication difficulties for autistic females. This has relevance for diagnostic, mental health and speech and language therapy services.
    • A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease

      Kyrtata, Natalia; Emsley, Hedley C. A.; Sparasci, Oli; Parkes, Laura M.; Dickie, Ben R.; email: ben.dickie@manchester.ac.uk (Frontiers Media S.A., 2021-05-20)
      Introduction: Alzheimer's disease (AD) is characterized by cerebral glucose hypometabolism. Hypometabolism may be partly due to reduced glucose transport at the blood-brain barrier (BBB) and across astrocytic and neuronal cell membranes. Glucose transporters (GLUTs) are integral membrane proteins responsible for moving glucose from the bloodstream to parenchymal cells where it is metabolized, and evidence indicates vascular and non-vascular GLUTs are altered in AD brains, a process which could starve the brain of glucose and accelerate cognitive decline. Here we review the literature on glucose transport alterations in AD from human and rodent studies. Methods: Literature published between 1st January 1946 and 1st November 2020 within EMBASE and MEDLINE databases was searched for the terms “glucose transporters” AND “Alzheimer's disease”. Human and rodent studies were included while reviews, letters, and in-vitro studies were excluded. Results: Forty-three studies fitting the inclusion criteria were identified, covering human (23 studies) and rodent (20 studies). Post-mortem studies showed consistent reductions in GLUT1 and GLUT3 in the hippocampus and cortex of AD brains, areas of the brain closely associated with AD pathology. Tracer studies in rodent models of AD and human AD also exhibit reduced uptake of glucose and glucose-analogs into the brain, supporting these findings. Longitudinal rodent studies clearly indicate that changes in GLUT1 and GLUT3 only occur after amyloid-β pathology is present, and several studies indicate amyloid-β itself may be responsible for GLUT changes. Furthermore, evidence from human and rodent studies suggest GLUT depletion has severe effects on brain function. A small number of studies show GLUT2 and GLUT12 are increased in AD. Anti-diabetic medications improved glucose transport capacity in AD subjects. Conclusions: GLUT1 and GLUT3 are reduced in hippocampal and cortical regions in patients and rodent models of AD, and may be caused by high levels of amyloid-β in these regions. GLUT3 reductions appear to precede the onset of clinical symptoms. GLUT2 and GLUT12 appear to increase and may have a compensatory role. Repurposing anti-diabetic drugs to modify glucose transport shows promising results in human studies of AD.
    • Acclimation of Photosynthesis to Changes in the Environment Results in Decreases of Oxidative Stress in Arabidopsis thaliana

      Karim, Mohd Fauzihan; Johnson, Giles N.; email: giles.johnson@manchester.ac.uk (Frontiers Media S.A., 2021-09-23)
      The dynamic acclimation of photosynthesis plays an important role in increasing the fitness of a plant under variable light environments. Since acclimation is partially mediated by a glucose-6-phosphate/phosphate translocator 2 (GPT2), this study examined whether plants lacking GPT2, which consequently have defective acclimation to increases in light, are more susceptible to oxidative stress. To understand this mechanism, we used the model plant Arabidopsis thaliana [accession Wassilewskija-4 (Ws-4)] and compared it with mutants lacking GPT2. The plants were then grown at low light (LL) at 100 μmol m−2 s−1 for 7 weeks. For the acclimation experiments, a set of plants from LL was transferred to 400 μmol m−2 s−1 conditions for 7 days. Biochemical and physiological analyses showed that the gpt2 mutant plants had significantly greater activity for ascorbate peroxidase (APX), guiacol peroxidase (GPOX), and superoxide dismutase (SOD). Furthermore, the mutant plants had significantly lower maximum quantum yields of photosynthesis (Fv/Fm). A microarray analysis also showed that gpt2 plants exhibited a greater induction of stress-related genes relative to wild-type (WT) plants. We then concluded that photosynthetic acclimation to a higher intensity of light protects plants against oxidative stress.
    • Adolescents' Understanding of What Causes Emotional Distress: A Qualitative Exploration in a Non-clinical Sample Using Ideal-Type Analysis

      O'Neill, Alisha; email: alisha.oneill@Manchester.ac.uk; Stapley, Emily; Stock, Sarah; Merrick, Hannah; Humphrey, Neil (Frontiers Media S.A., 2021-05-24)
      Background: There is increased interest in early intervention and prevention of mental health difficulties during adolescence; thus, we are seeing increased efforts to optimize well-being during this epoch. Positive emotional experiences are a central component of overall well-being. However, research exploring what adolescents perceive to be the cause(s) of their emotional difficulties is lacking. Improving understanding of this issue within non-clinical adolescent groups may provide useful insight into how to develop strategies to support young people as they navigate emotional difficulties. Objectives: The aim of this research was to explore if meaningful categories of perceived cause(s) for emotional distress exist for non-clinical adolescent groups. Methods: The data for this study were drawn from interviews across 6 sites in England conducted as part of the 5-year national evaluation of the HeadStart Learning Programme. The sample comprised of 32 young people aged 11–12 years from the first annual wave of qualitative data collection in 2017. Ideal type analysis—a qualitative form of person-centered analysis—was used to construct a typology of adolescents perceived cause(s) for emotional distress. Findings: We identified five distinct categories of perceived cause: (1) perceived lack of control; (2) unfair treatment; (3) others, their actions and judgements as the catalyst; (4) concerns for self and others; and, (5) self as cause. Conclusions: Our findings illustrate that distinct categories for perceived cause of emotional distress exist among adolescents considered to be “at risk” of developing mental health difficulties, which provides a foundation for future necessary work seeking to investigate the possible link between perceived cause for emotional distress and help-seeking behavior among sub-clinical groups.
    • Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing

      Szondi, Denis C.; Wong, Jason K.; Vardy, Leah A.; Cruickshank, Sheena M.; email: sheena.cruickshank@manchester.ac.uk (Frontiers Media S.A., 2021-10-29)
      Arginase (ARG) represents an important evolutionarily conserved enzyme that is expressed by multiple cell types in the skin. Arg acts as the mediator of the last step of the urea cycle, thus providing protection against excessive ammonia under homeostatic conditions through the production of L-ornithine and urea. L-ornithine represents the intersection point between the ARG-dependent pathways and the urea cycle, therefore contributing to cell detoxification, proliferation and collagen production. The ARG pathways help balance pro- and anti-inflammatory responses in the context of wound healing. However, local and systemic dysfunctionalities of the ARG pathways have been shown to contribute to the hindrance of the healing process and the occurrence of chronic wounds. This review discusses the functions of ARG in macrophages and fibroblasts while detailing the deleterious implications of a malfunctioning ARG enzyme in chronic skin conditions such as leg ulcers. The review also highlights how ARG links with the microbiota and how this impacts on infected chronic wounds. Lastly, the review depicts chronic wound treatments targeting the ARG pathway, alongside future diagnosis and treatment perspectives.
    • Autosomal Recessive Cutis Laxa 1C Mutations Disrupt the Structure and Interactions of Latent TGFβ Binding Protein-4

      Alanazi, Yasmene F.; Lockhart-Cairns, Michael P.; Cain, Stuart A.; Jowitt, Thomas A.; Weiss, Anthony S.; Baldock, Clair; email: clair.baldock@manchester.ac.uk (Frontiers Media S.A., 2021-09-03)
      Latent TGFβ binding protein-4 (LTBP4) is a multi-domain glycoprotein, essential for regulating the extracellular bioavailability of TGFβ and assembly of elastic fibre proteins, fibrillin-1 and tropoelastin. LTBP4 mutations are linked to autosomal recessive cutis laxa type 1C (ARCL1C), a rare congenital disease characterised by high mortality and severely disrupted connective tissues. Despite the importance of LTBP4, the structure and molecular consequences of disease mutations are unknown. Therefore, we analysed the structural and functional consequences of three ARCL1C causing point mutations which effect highly conserved cysteine residues. Our structural and biophysical data show that the LTBP4 N- and C-terminal regions are monomeric in solution and adopt extended conformations with the mutations resulting in subtle changes to their conformation. Similar to LTBP1, the N-terminal region is relatively inflexible, whereas the C-terminal region is flexible. Interaction studies show that one C-terminal mutation slightly decreases binding to fibrillin-1. We also found that the LTBP4 C-terminal region directly interacts with tropoelastin which is perturbed by both C-terminal ARCL1C mutations, whereas an N-terminal mutation increased binding to fibulin-4 but did not affect the interaction with heparan sulphate. Our results suggest that LTBP4 mutations contribute to ARCL1C by disrupting the structure and interactions of LTBP4 which are essential for elastogenesis in a range of mammalian connective tissues.
    • Blockchain Native Data Linkage

      Cunningham, James; email: james.a.cunningham@manchester.ac.uk; Davidge, Gail; Davies, Nigel; Devaney, Sarah; Holm, Søren; Harding, Mike; Leeming, Gary; Neumann, Victoria; Ainsworth, John (Frontiers Media S.A., 2021-10-29)
      Data providers holding sensitive medical data often need to exchange data pertaining to patients for whom they hold particular data. This involves requesting information from other providers to augment the data they hold. However, revealing the superset of identifiers for which a provider requires information can, in itself, leak sensitive private data. Data linkage services exist to facilitate the exchange of anonymized identifiers between data providers. Reliance on third parties to provide these services still raises issues around the trust, privacy and security of such implementations. The rise and use of blockchain and distributed ledger technologies over the last decade has, alongside innovation and disruption in the financial sphere, also brought to the fore and refined the use of associated privacy-preserving cryptographic protocols and techniques. These techniques are now being adopted and used in fields removed from the original financial use cases. In this paper we present a combination of a blockchain-native auditing and trust-enabling environment alongside a query exchange protocol. This allows the exchange of sets of patient identifiers between data providers in such a way that only identifiers lying in the intersection of sets of identifiers are revealed and shared, allowing further secure and privacy-preserving exchange of medical information to be carried out between the two parties. We present the design and implementation of a system demonstrating the effectiveness of these exchange protocols giving a reference architecture for the implementation of such a system.
    • Clinical Trials and Outcome Measures in Adults With Hearing Loss

      Munro, Kevin J.; email: kevin.munro@manchester.ac.uk; Whitmer, William M.; Heinrich, Antje (Frontiers Media S.A., 2021-11-05)
      Clinical trials are designed to evaluate interventions that prevent, diagnose or treat a health condition and provide the evidence base for improving practice in health care. Many health professionals, including those working within or allied to hearing health, are expected to conduct or contribute to clinical trials. Recent systematic reviews of clinical trials reveal a dearth of high quality evidence in almost all areas of hearing health practice. By providing an overview of important steps and considerations concerning the design, analysis and conduct of trials, this article aims to give guidance to hearing health professionals about the key elements that define the quality of a trial. The article starts out by situating clinical trials within the greater scope of clinical evidence, then discusses the elements of a PICO-style research question. Subsequently, various methodological considerations are discussed including design, randomization, blinding, and outcome measures. Because the literature on outcome measures within hearing health is as confusing as it is voluminous, particular focus is given to discussing how hearing-related outcome measures affect clinical trials. This focus encompasses how the choice of measurement instrument(s) affects interpretation, how the accuracy of a measure can be estimated, how this affects the interpretation of results, and if differences are statistically, perceptually and/or clinically meaningful to the target population, people with hearing loss.
    • Continuous Magnitude Production of Loudness

      Schlittenlacher, Josef; email: josef.schlittenlacher@manchester.ac.uk; Ellermeier, Wolfgang (Frontiers Media S.A., 2021-05-11)
      Continuous magnitude estimation and continuous cross-modality matching with line length can efficiently track the momentary loudness of time-varying sounds in behavioural experiments. These methods are known to be prone to systematic biases but may be checked for consistency using their counterpart, magnitude production. Thus, in Experiment 1, we performed such an evaluation for time-varying sounds. Twenty participants produced continuous cross-modality matches to assess the momentary loudness of fourteen songs by continuously adjusting the length of a line. In Experiment 2, the resulting temporal line length profile for each excerpt was played back like a video together with the given song and participants were asked to continuously adjust the volume to match the momentary line length. The recorded temporal line length profile, however, was manipulated for segments with durations between 7 to 12 s by eight factors between 0.5 and 2, corresponding to expected differences in adjusted level of −10, −6, −3, −1, 1, 3, 6, and 10 dB according to Stevens’s power law for loudness. The average adjustments 5 s after the onset of the change were −3.3, −2.4, −1.0, −0.2, 0.2, 1.4, 2.4, and 4.4 dB. Smaller adjustments than predicted by the power law are in line with magnitude-production results by Stevens and co-workers due to “regression effects.” Continuous cross-modality matches of line length turned out to be consistent with current loudness models, and by passing the consistency check with cross-modal productions, demonstrate that the method is suited to track the momentary loudness of time-varying sounds.
    • Dance at Home for People With Parkinson's During COVID-19 and Beyond: Participation, Perceptions, and Prospects

      Bek, Judith; email: judith.bek@manchester.ac.uk; Groves, Michelle; Leventhal, David; Poliakoff, Ellen (Frontiers Media S.A., 2021-05-31)
      Emerging evidence shows that dance can provide both physical and non-physical benefits for people living with Parkinson's disease (PD). The suspension of in-person dance classes during the COVID-19 pandemic necessitated a transition to remote provision via live and recorded digital media. An online survey explored accessibility of and engagement with home-based dance programs, as well as potential benefits and processes involved in participation. The survey was co-developed by researchers and dance program providers, with input from people with PD and physiotherapists. Responses were collected from 276 individuals, including 178 current users of home-based programs, the majority of whom were participating at least once per week. Among respondents not currently using digital resources, lack of knowledge and motivation were the primary barriers. Most participants (94.9%) reported that home based practise provided some benefits, including physical (e.g., balance, posture) and non-physical (e.g., mood, confidence) improvements. Participants valued the convenience and flexibility of digital participation, but noted limitations including reductions in social interaction, support from instructors and peers, and motivation. There was a strong preference (70.8%) for continuing with home-based practise alongside in-person classes in the future. The results indicate that at-home dance is accessible and usable for people with PD, and that some of the previously-reported benefits of dance may be replicated in this context. Digital dance programs will likely remain a key element of future provision for people with PD, and the present findings will inform further development of resources and research into mechanisms and outcomes of home-based dance participation.
    • Differences in Characteristics and Ambulance Pathway Adherence Between Strokes and Mimics Presenting to a Large UK Centralized Hyper Acute Stroke Unit (HASU)

      Sammut-Powell, Camilla; email: Camilla.sammut-powell@manchester.ac.uk; Ashton, Christopher; Paroutoglou, Kyriaki; Parry-Jones, Adrian (Frontiers Media S.A., 2021-05-10)
      Background: In Greater Manchester (GM), prehospital clinicians use the Face Arm Speech Test (FAST) to identify suspected stroke patients alongside pathway exclusions. Within the centralized stroke service, patients with a suspected stroke are taken directly to a Hyper Acute Stroke Unit (HASU), often bypassing their local emergency department (ED). However, many of these patients are experiencing an illness that looks like a stroke but is not a stroke. The data collected in the prehospital setting is rarely used in research yet could give valuable insights into the performance of the pathway. Aim: To evaluate the presenting symptoms and final diagnoses of prehospital suspected strokes and to evaluate the adherence of prehospital stroke pathway exclusions. Methods: We analyzed data from all patients brought in by ambulance and admitted on the stroke pathway between 01/09/15 and 28/02/17. Patient demographics and all data recorded in the prehospital setting were evaluated to identify differences in stroke, TIA, and mimic patients. Pathway adherence was assessed according to whether the patient was local or out-of-area (OOA) and bypassed their local ED. Results: A total of 4,216 suspected strokes were identified: 2,213 (52.5%) had a final diagnosis of stroke, 492 (11.7%) experienced a transient ischemic attack (TIA), and 1,511 (35.8%) were stroke mimics. There were 714 (16.9%) patients that were identified as having at least one pathway exclusion or were FAST negative, of which 270 (37.8%) experienced a stroke. The proportion of strokes was significantly lower in those with a pathway exclusion (41.8 vs. 53.5%; p < 0.001) and the proportion of breaches tended to be comparable or higher in the local population. Discussion: There are high volumes of stroke mimics but identified differences indicate there is an opportunity to better utilize prehospital data. Ambulance clinicians were able to correctly overrule FAST negative results and the volume of these suggest that FAST alone may be too restrictive.
    • Editorial: Cooperation and Coordination in the Family

      Savage, James L.; email: james.savage@cantab.net; Hinde, Camilla A.; Johnstone, Rufus A. (Frontiers Media S.A., 2020-12-07)
    • Editorial: New Drug Targets for Proteotoxicity in Cardiometabolic Diseases

      Ren, Jun; email: jren@uw.edu; Wang, Xin; email: xin.wang@manchester.ac.uk; Zhang, Yingmei; email: zhangym197951@126.com (Frontiers Media S.A., 2021-09-16)
    • Equivalence, Justice, Injustice – Health and Social Care Decision Making in Relation to Prison Populations

      Shepherd, Andrew; email: andrew.shepherd-2@manchester.ac.uk; Hewson, Tom; Hard, Jake; Green, Russell; Shaw, Jennifer (Frontiers Media S.A., 2021-07-14)
      Prisons represent sites of singular healthcare need–characterized by high levels of distress and disorder. In many jurisdictions, practitioners are ethically charged with delivering healthcare that is “equivalent” to that available in the wider community. This claim has been much debated–yet the emergence of a global coronavirus pandemic has highlighted the arguments in a particularly stark manner. In the following conceptual analysis, we explore the emergent discourse of the coronavirus and consider its particular significance for prison healthcare decision making and the concept of equivalence. For example, both the coronavirus pandemic and practice of prison incarceration induce a sense of varied temporality: The discourse of prison is replete in this area–such as the concept of “hard time.” Alongside this, the discourse in relation to coronavirus has highlighted two competing modes of temporal understanding: The political–where the pandemic is conceptualized as has having a discrete “beginning and end”, and the scientific–where the “new normal” reflects the incorporation of the “novel” coronavirus into the wider ecology. The impact of these disparate understandings on the prison population is complex: “Locking down” prisoners–to safeguard the vulnerable against infection–is relatively simple, yet it has traumatic repercussions with respect to liberty and psychosocial health. Easing lockdown, by contrast, is a difficult endeavor and risks collision between the temporalities of prison–where “hard time” is accentuated by separation from the “real world”–the political and the scientific. Whither then the concept of equivalence in relation to a field that is definitively non-equivalent? How can practitioners and policy makers maintain a just ethical stance in relation to the allocation of resources when it comes to a politically marginalized yet manifestly vulnerable population? We argue that further debate and consideration are required in this field–and propose a framework for such discussion.
    • Extrinsic and Existential Mortality Risk in Reproductive Decision-Making: Examining the Effects of COVID-19 Experience and Climate Change Beliefs

      Gordon, David S.; email: david.gordon@chester.ac.uk (Frontiers Media S.A., 2021-06-11)
      While the COVID-19 pandemic has presented an immediate risk to human life around the world, climate change poses an arguably greater—although less immediate—threat to our species’ survival. Within the framework of life-history theory (LHT), this pre-registered study investigated whether extrinsic risk (i.e., external factors that pose a risk to an individual’s life, e.g., COVID-19) and existential risk (i.e., risks with outcomes that threaten the existence of humans as a species, e.g., climate change) had similar or different relationships with reproductive decision-making. A UK representative sample of 325 participants between 18 and 35 years of age was asked to indicate their ideal number of children, ideal age to start having children, and whether their desire for a child had recently changed. Participants were asked about their experiences of COVID-19 and given a series of scales with which to assess their beliefs about climate change. In support of LHT, the study found evidence that knowing people who had been hospitalized with or died of COVID-19 was associated with a greater ideal number of children. Conversely, there was no clear evidence of a relationship between climate change beliefs and reproductive decision-making. The repercussions for understanding how we interpret and respond to different forms of mortality risk are discussed.
    • Fabrication and Mechanical Performance of Graphene Nanoplatelet/Glass Fiber Reinforced Polymer Hybrid Composites

      Yao, Xudan; email: xudan.yao@manchester.ac.uk; Kinloch, Ian A.; Bissett, Mark A.; email: mark.bissett@manchester.ac.uk (Frontiers Media S.A., 2021-11-16)
      Glass fiber reinforced polymer (GFRP) composites are promising alternatives for the traditional carbon steel pipes used in the oil and gas industry due to their corrosion and chemical resistance. However, the out-of-plane mechanical properties of GFRPs still need further improvement to achieve this goal. Hence, in this work, two methods combining either vacuum mixing or spray coating with vacuum-assisted resin infusion were studied to fabricate graphene nanoplatelet (GNP)/GFRP hybrid composites. The former method resulted in a severe filtering effect, where the GNPs were not evenly distributed throughout the final composite, whereas the latter process resulted in a uniform GNP distribution on the glass fabrics. The addition of GNPs showed no modest contribution to the tensile performance of the GFRP composites due to the relatively high volume and in-plane alignment of the glass fibers. However, the GNPs did improve the flexural properties of GFRP with an optimal loading of 0.15 wt% GNPs, resulting in flexural strength and modulus increases of 6.8 and 1.6%, respectively. This work indicates how GNPs can be advantageous for out-of-plane mechanical reinforcement in fiber-reinforced composites.
    • Heart's Ease: Eudaimonia, Musicking in the Pandemic, and Its Implications for Music Education

      Boyce-Tillman, June; email: june.boyce-tillman@winchester.ac.uk (Frontiers Media S.A., 2021-09-09)
      This article will review the themes found in the literature on eudaimonia: ethical behaviour, a sense of meaning and purpose, autonomy – being able to make wise decisions and manage behaviour, contemplation, relationship with spirits of the ancestors and celestial beings and relationships of mutuality, respect. It will use these to critique various events online during the pandemic, such as the Embodiment conference, the SHIFT conference and the ZOOM peace choir. These developments related to music and wellbeing will be used to interrogate the purposes of music education and what might be learned from these new developments in relation to technology in relation to themes, such as values, orality and literacy, process and product.
    • Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis

      Brady, Chloe A.; email: chloe.brady@manchester.ac.uk; Williams, Charlotte; Batra, Gauri; Church, Elaine; Tower, Clare L.; Crocker, Ian P.; Heazell, Alexander E. P. (Frontiers Media S.A., 2021-10-18)
      Chronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta. Given its proposed immunological etiology, current treatments include aspirin, heparin, and immunomodulatory agents. However, the rationale for these medications is largely based upon small case series and reports as there is a lack of larger studies investigating treatment efficacy. Therefore, this study sought to determine whether inclusion of immunomodulatory medications was effective at reducing the severity of lesions and improving pregnancy outcomes in subsequent pregnancies. Thirty-three women with a history of CHI in at least one pregnancy (index case) were identified retrospectively through medical records. Twenty-eight participants presented with a first subsequent pregnancy and a further 11 with a second subsequent pregnancy at a specialist clinic for pregnancy after loss. Data on maternal demographics, medical history, medication, pregnancy outcome, and placental pathology was collected and compared between pregnancies. Twenty-seven (69%) subsequent pregnancies were treated with at least one or both of prednisolone and hydroxychloroquine. Inclusion of at least one immunomodulatory agent in treatment regimen resulted in an almost 25% increase in overall livebirth rate (61.5 vs. 86.2%). In women treated with immunomodulatory medication a greater proportion of placentas had reduced severity of lesions compared to those treated without (86.7 vs. 33.3%, respectively). A reduction in CHI severity was associated with a 62.3% improvement in livebirth rate compared to those where severity remained unchanged in relation to the index case. These data provide preliminary evidence that the use of immunomodulatory medication in the management of CHI improves histopathological lesions and the chance of livebirth in subsequent pregnancies. Due to CHI's rarity and ethical and feasibility issues, randomized controlled trials in affected women are challenging to conduct. As a result, collaboration between centers is required in future to increase study sample sizes and elucidate the mechanisms of hydroxychloroquine and prednisolone in reducing pathology.