The role of macrophage migration inhibitory factor in airways disease

Chronic obstructive pulmonary disease (COPD) and severe asthma are progressive chronic inflammatory diseases of the airways. Both diseases are characterised by airflow limitation and share some pulmonary symptoms. However they have distinct inflammatory cell signatures and differ in response to corticosteroid (CS) treatment. Most asthmatic patients control their disease with CS, with a few showing a relative CS resistance; however COPD patients show little or no improvement with CS and are CS insensitive. Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory mediator whose function is yet to be fully elucidated. MIF has been shown to counter-act the immunosuppressive action of CS. MIF is elevated in chronic diseases such as asthma and atherosclerosis. The role of MIF in COPD has not been investigated and its role in asthma is not fully understood. MIF inhibition attenuated ozone-induced airway inflammation and lung function in vivo but did not affect CS sensitivity. MIF expression did not vary between stable COPD patients and controls. Pro-inflammatory effects of MIF were investigated in THP-1 monocytes and primary cells. There was no clear role for MIF in LPS-induced inflammation. MIF modulated the transactivation functions of CS in THP-1 cells. Finally I took an unbiased approach to generate new hypotheses for MIF function using proteomic and transcriptomic techniques. The RIG-I-like pathway was identified by proteomics as a novel target pathway and was investigated in THP-1 cells and human BAL macrophage samples following viral infection. The role of MIF in airway inflammation remains unclear and results demonstrated here show MIF function does not necessarily translate from mouse to humans. MIF does not seem to have a role in the inflammation of stable disease. The proteomic data suggests that the association between viral infection, MIF and CS in regulating CS sensitivity in COPD and severe asthma should be investigated.Open Acces

Student Engagement in a Digital Context: 360 Immersive Video and Feedback

This case study discusses a recent small-scale research project that investigates the integration of 360 camera and head mounted display units (HMD’s) to enhance formative video feedback in Dance Technique in Higher Education (HE). The project was funded by the Teaching and Learning Innovation Fund at the University of Lincoln and led by academics in the School of Fine and Performing Arts. The project took place throughout the academic year 2020/2021 and was designed to respond to the challenges the pandemic had created for Dance in HE. A group of 10 final year BA Hons Dance university students chose to participate in the project for the duration of the year

Amino acid racemization dating of marine shells: a mound of possibilities

Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization(AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscanspecies. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins(by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea.Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world

Amino acid racemization dating of marine shells: a mound of possibilities

Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization(AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscanspecies. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins(by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea.Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world

Mental Health Admissions to Paediatric Wards Study (MAPS): protocol of a prospective study of mental health admissions to paediatric wards in England using surveillance and qualitative methods

INTRODUCTION: Children and young people (CYP) presenting with a mental health (MH) crisis are frequently admitted to general acute paediatric wards as a place of safety. Prior to the pandemic, a survey in England showed that CYP occupied 6% of general paediatric inpatient beds due to an MH crisis, and there have been longstanding concerns about the quality of care to support these patients in this setting. MAPS aims to generate a Theory of Change (ToC) model to improve the quality of care for CYP admitted to acute paediatric services after presenting with an MH crisis. Here, we describe work packages (WPs) 2 and 3 of the study, which have been granted ethics approval. METHODS AND ANALYSIS: We will undertake a national (England), sequential, mixed-methods study to inform a ToC framework alongside a stakeholder group consisting of patients, families/carers and healthcare professionals (HCPs). Our study consists of four WPs undertaken over 30 months. WP2 is limited to working with stakeholders to develop a data collection instrument and then use this in a prospective study of MH admissions over 6 months in 15 purposively recruited acute paediatric wards across England. WP3 consists of gathering the views of CYP, their families/carers and HCPs during admissions using semistructured interviews. ETHICS AND DISSEMINATION: WP2 and WP3 received ethical approval (ref: 23/LO/0349). We will publish the overall synthesis of data and the final ToC to improve care of CYP with MH crisis admitted to general acute paediatric settings. As co-producers of the ToC, we will work with our stakeholder group to ensure wide dissemination of findings. Potential impacts will be upon service development, new models of care, training and workforce planning. PROSPERO REGISTRATION NUMBER: CRD42022350655

Mental Health Admissions to Paediatric Wards Study (MAPS): a protocol for the analysis of Hospital Episode Statistics (HES) data

INTRODUCTION: Children and young people (CYP) presenting with a mental health (MH) crisis are frequently admitted to general acute paediatric wards as a place of safety. Prior to the pandemic, a survey in England showed that CYP occupied 6% of general paediatric inpatient beds due to an MH crisis, and there have been longstanding concerns about the quality of care to support these patients in this setting. Mental Health Admissions to Paediatric Wards Study aims to generate a theory of change (ToC) model to improve the quality of care for CYP admitted to acute paediatric services after presenting in a MH crisis. METHODS AND ANALYSIS: We will undertake a national (England), sequential, mixed methods study to inform a ToC framework alongside a stakeholder group consisting of patients, families/carers and healthcare professionals (HCPs). Our study consists of four work packages (WP) undertaken over 30 months. WP1 is limited to using national routine administrative data to identify and characterise trends in MH admissions in acute paediatric wards in England between 2015- 2022. ETHICS AND DISSEMINATION: WP1 received ethical approval (Ref 23/NW/0192). We will publish the overall synthesis of data and the final ToC to improve care of CYP with MH crisis admitted to general acute paediatric settings. As coproducers of the ToC, we will work with our stakeholder group to ensure wide dissemination of findings. Potential impacts will be on service development, new models of care, training and workforce planning

Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals:study protocol for a randomised controlled trial

BACKGROUND: Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis. METHODS/DESIGN: The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18–60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain. DISCUSSION: Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics. TRIAL REGISTRATION: UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013

“Lest we forget” : An overview of Australia’s response to the recovery and identification of unrecovered historic military remains

Peer reviewedPostprin