• Non-invasive objective tools for quantitative assessment of skin scarring.

      Ud-Din, Sara; email: sara.ud-din@manchester.ac.uk; Bayat, Ardeshir; email: ardeshir.bayat@manchester.ac.uk (2021-05-08)
      Multiple treatment modalities are utilised in the management of skin scarring, however, due to high recurrence rates and unknown resolution rates it can be difficult to assess if treatment is suitable or effective for the individual patient in particular in the case of raised dermal scarring. Therefore, it is necessary to evaluate these treatments and provide accurate scar assessment pre- & post-therapy in order to quantify scar characteristics using objective assessment tools, particularly non-invasive devices. Recent Advances: There have been a number of emerging non-invasive objective quantitative devices which assess specific scar parameters such as pliability, firmness, volume, colour, perfusion and depth. These can include 3-dimensional imaging, optical coherence tomography, in vivo confocal microscopy, full-field laser perfusion imaging and spectrophotometric intracutaneous analysis. Clinical assessment and grading scales are most commonly used to assess scarring, however, there is a need for more objective quantitative measures to monitor their maturation and response to therapy. Currently, there is no consensus as to which objective measuring device is most optimal when assessing skin scarring. There is a need for a predictor tool which allows early implementation of treatment and addresses diagnosis, therapy and prognosis. Future technological advances and further validation of non-invasive objective scar assessment tools is essential. At present there is a greater emphasis on tools to assess the physical scar parameters rather than the physiological characteristics. Therefore, it is essential to develop a tool which measures the metabolic and cellular activity in scars in order to tailor treatment to each individual.
    • Non-Newtonian Droplet Generation in a Cross-Junction Microfluidic Channel

      Fatehifar, Maryam; orcid: 0000-0002-8770-729X; email: maryam.fatehifar@postgrad.manchester.ac.uk; Revell, Alistair; orcid: 0000-0001-7435-1506; email: alistair.revell@manchester.ac.uk; Jabbari, Masoud; orcid: 0000-0003-3615-969X; email: m.jabbari@manchester.ac.uk (MDPI, 2021-06-09)
      A two-dimensional CFD model based on volume-of-fluid (VOF) is introduced to examine droplet generation in a cross-junction microfluidic using an open-source software, OpenFOAM together with an interFoam solver. Non-Newtonian power-law droplets in Newtonian liquid is numerically studied and its effect on droplet size and detachment time in three different regimes, i.e., squeezing, dripping and jetting, are investigated. To understand the droplet formation mechanism, the shear-thinning behaviour was enhanced by increasing the polymer concentrations in the dispersed phase. It is observed that by choosing a shear-dependent fluid, droplet size decreases compared to Newtonian fluids while detachment time increases due to higher apparent viscosity. Moreover, the rheological parameters—n and K in the power-law model—impose a considerable effect on the droplet size and detachment time, especially in the dripping and jetting regimes. Those parameters also have the potential to change the formation regime if the capillary number (Ca) is high enough. This work extends the understanding of non-Newtonian droplet formation in microfluidics to control the droplet characteristics in applications involving shear-thinning polymeric solutions.
    • Non-territorial GPS-tagged golden eagles Aquila chrysaetos at two Scottish wind farms: Avoidance influenced by preferred habitat distribution, wind speed and blade motion status

      editor: Magar, Vanesa; Fielding, Alan H.; Anderson, David; Benn, Stuart; Dennis, Roy; Geary, Matthew; Weston, Ewan; Whitfield, D. Philip; orcid: 0000-0003-4255-7782; email: phil.whitfield@natural-research.org (Public Library of Science, 2021-08-05)
      Wind farms can have two broad potential adverse effects on birds via antagonistic processes: displacement from the vicinity of turbines (avoidance), or death through collision with rotating turbine blades. These effects may not be mutually exclusive. Using detailed data from 99 turbines at two wind farms in central Scotland and thousands of GPS-telemetry data from dispersing golden eagles, we tested three hypotheses. Before-and-after-operation analyses supported the hypothesis of avoidance: displacement was reduced at turbine locations in more preferred habitat and with more preferred habitat nearby. After-operation analyses (i.e. from the period when turbines were operational) showed that at higher wind speeds and in highly preferred habitat eagles were less wary of turbines with motionless blades: rejecting our second hypothesis. Our third hypothesis was supported, since at higher wind speeds eagles flew closer to operational turbines; especially–once more–turbines in more preferred habitat. After operation, eagles effectively abandoned inner turbine locations, and flight line records close to rotor blades were rare. While our study indicated that whole-wind farm functional habitat loss through avoidance was the substantial adverse impact, we make recommendations on future wind farm design to minimise collision risk further. These largely entail developers avoiding outer turbine locations which are in and surrounded by swathes of preferred habitat. Our study illustrates the insights which detailed case studies of large raptors at wind farms can bring and emphasises that the balance between avoidance and collision can have several influences.
    • Non-territorial GPS-tagged golden eagles Aquila chrysaetos at two Scottish wind farms: Avoidance influenced by preferred habitat distribution, wind speed and blade motion status.

      Fielding, Alan H; Anderson, David; Benn, Stuart; Dennis, Roy; Geary, Matthew; Weston, Ewan; Whitfield, D Philip; orcid: 0000-0003-4255-7782 (2021-08-05)
      Wind farms can have two broad potential adverse effects on birds via antagonistic processes: displacement from the vicinity of turbines (avoidance), or death through collision with rotating turbine blades. These effects may not be mutually exclusive. Using detailed data from 99 turbines at two wind farms in central Scotland and thousands of GPS-telemetry data from dispersing golden eagles, we tested three hypotheses. Before-and-after-operation analyses supported the hypothesis of avoidance: displacement was reduced at turbine locations in more preferred habitat and with more preferred habitat nearby. After-operation analyses (i.e. from the period when turbines were operational) showed that at higher wind speeds and in highly preferred habitat eagles were less wary of turbines with motionless blades: rejecting our second hypothesis. Our third hypothesis was supported, since at higher wind speeds eagles flew closer to operational turbines; especially-once more-turbines in more preferred habitat. After operation, eagles effectively abandoned inner turbine locations, and flight line records close to rotor blades were rare. While our study indicated that whole-wind farm functional habitat loss through avoidance was the substantial adverse impact, we make recommendations on future wind farm design to minimise collision risk further. These largely entail developers avoiding outer turbine locations which are in and surrounded by swathes of preferred habitat. Our study illustrates the insights which detailed case studies of large raptors at wind farms can bring and emphasises that the balance between avoidance and collision can have several influences.
    • Norwegian youngsters’ perceptions of physical education: exploring the implications for mental health

      Røset, Linda; orcid: 0000-0003-3377-7636; Green, Ken; orcid: 0000-0003-1692-7065; Thurston, Miranda; orcid: 0000-0001-7779-3836 (Informa UK Limited, 2019-06-24)
    • Not only laboratory to clinic: the translational work of William S. C. Copeman in rheumatology

      Worboys, Michael; orcid: 0000-0001-8583-7931; email: michael.worboys@manchester.ac.uk; Toon, Elizabeth (Springer International Publishing, 2020-08-06)
      Abstract: Since the arrival of Translational Medicine (TM), as both a term and movement in the late 1990s, it has been associated almost exclusively with attempts to accelerate the “translation” of research-laboratory findings to improve efficacy and outcomes in clinical practice (Krueger et al. in Hist Philos Life Sci 41:57, 2019). This framing privileges one source of change in medicine, that from bench-to-bedside. In this article we dig into the history of translation research to identify and discuss three other types of translational work in medicine that can also reshape ideas, practices, institutions, behaviours, or all of these, to produce transformations in clinical effectiveness. These are: (1) making accessible state-of-the-art knowledge and best practice across the medical profession; (2) remodelling and creating institutions to better develop and make available specialist knowledge and practice; and (3) improving public and patient understandings of disease prevention, symptoms and treatments. We do so by examining the work of William S. C. Copeman, a dominant figure in British rheumatology from the 1930 through the late 1960s. Throughout his long career, Copeman blended approaches to “translation” in order to produce transformative change in clinical medicine, making his work an exemplar of our expanded notion of TM.
    • Notch Signalling in Breast Development and Cancer

      Edwards, Abigail; Brennan, Keith; email: keith.brennan@manchester.ac.uk (Frontiers Media S.A., 2021-07-06)
      The Notch signalling pathway is a highly conserved developmental signalling pathway, with vital roles in determining cell fate during embryonic development and tissue homeostasis. Aberrant Notch signalling has been implicated in many disease pathologies, including cancer. In this review, we will outline the mechanism and regulation of the Notch signalling pathway. We will also outline the role Notch signalling plays in normal mammary gland development and how Notch signalling is implicated in breast cancer tumorigenesis and progression. We will cover how Notch signalling controls several different hallmarks of cancer within epithelial cells with sections focussed on its roles in proliferation, apoptosis, invasion, and metastasis. We will provide evidence for Notch signalling in the breast cancer stem cell phenotype, which also has implications for therapy resistance and disease relapse in breast cancer patients. Finally, we will summarise the developments in therapeutic targeting of Notch signalling, and the pros and cons of this approach for the treatment of breast cancer.
    • Notes on the genus Chinattus Logunov, 1999 from India, Pakistan and Nepal (Arachnida: Araneae: Salticidae).

      Logunov, Dmitri V; email: dmitri.v.logunov@manchester.ac.uk (2021-07-29)
      A new speciesChinattus mikhailovi sp. nov. (♂♀, from Pakistan, Peshawar)is diagnosed, described and illustrated. New records of Chinattus validus (Xie, Peng et Kim, 1993) from Nepal, India (Himachal Pradesh) and Vietnam, and C. chichila Logunov, 2003 from Nepal are presented. The collecting localities of all three species are mapped. A brief discussion of the state of knowledge of the genus Chinattus Logunov, 1999 is provided as well.
    • Nothing about us without us: involving patient collaborators for machine learning applications in rheumatology.

      Shoop-Worrall, Stephanie J W; orcid: 0000-0002-9441-5535; email: stephanie.shoop-worrall@manchester.ac.uk; Cresswell, Katherine; Bolger, Imogen; Dillon, Beth; Hyrich, Kimme L; orcid: 0000-0001-8242-9262; Geifman, Nophar; Members of the CLUSTER consortium (2021-07-05)
      Novel machine learning methods open the door to advances in rheumatology through application to complex, high-dimensional data, otherwise difficult to analyse. Results from such efforts could provide better classification of disease, decision support for therapy selection, and automated interpretation of clinical images. Nevertheless, such data-driven approaches could potentially model noise, or miss true clinical phenomena. One proposed solution to ensure clinically meaningful machine learning models is to involve primary stakeholders in their development and interpretation. Including patient and health care professionals' input and priorities, in combination with statistical fit measures, allows for any resulting models to be well fit, meaningful, and fit for practice in the wider rheumatological community. Here we describe outputs from workshops that involved healthcare professionals, and young people from the Your Rheum Young Person's Advisory Group, in the development of complex machine learning models. These were developed to better describe trajectory of early juvenile idiopathic arthritis disease, as part of the CLUSTER consortium. We further provide key instructions for reproducibility of this process.Involving people living with, and managing, a disease investigated using machine learning techniques, is feasible, impactful and empowering for all those involved. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.]
    • Novel methodology to assess the effect of contouring variation on treatment outcome

      Jenkins, Alexander; Mullen, Thomas Soares; Johnson‐Hart, Corinne; Green, Andrew; McWilliam, Alan; Aznar, Marianne; van Herk, Marcel; Vasquez Osorio, Eliana; email: eliana.vasquezosorio@manchester.ac.uk (2021-04-24)
      Purpose: Contouring variation is one of the largest systematic uncertainties in radiotherapy, yet its effect on clinical outcome has never been analyzed quantitatively. We propose a novel, robust methodology to locally quantify target contour variation in a large patient cohort and find where this variation correlates with treatment outcome. We demonstrate its use on biochemical recurrence for prostate cancer patients. Method: We propose to compare each patient’s target contours to a consistent and unbiased reference. This reference was created by auto‐contouring each patient’s target using an externally trained deep learning algorithm. Local contour deviation measured from the reference to the manual contour was projected to a common frame of reference, creating contour deviation maps for each patient. By stacking the contour deviation maps, time to event was modeled pixel‐wise using a multivariate Cox proportional hazards model (CPHM). Hazard ratio (HR) maps for each covariate were created, and regions of significance found using cluster‐based permutation testing on the z‐statistics. This methodology was applied to clinical target volume (CTV) contours, containing only the prostate gland, from 232 intermediate‐ and high‐risk prostate cancer patients. The reference contours were created using ADMIRE® v3.4 (Elekta AB, Sweden). Local contour deviations were computed in a spherical coordinate frame, where differences between reference and clinical contours were projected in a 2D map corresponding to sampling across the coronal and transverse angles every 3°. Time to biochemical recurrence was modeled using the pixel‐wise CPHM analysis accounting for contour deviation, patient age, Gleason score, and treated CTV volume. Results: We successfully applied the proposed methodology to a large patient cohort containing data from 232 patients. In this patient cohort, our analysis highlighted regions where the contour variation was related to biochemical recurrence, producing expected and unexpected results: (a) the interface between prostate–bladder and prostate–seminal vesicle interfaces where increase in the manual contour relative to the reference was related to a reduction of risk of biochemical recurrence by 4–8% per mm and (b) the prostate's right, anterior and posterior regions where an increase in the manual contour relative to the reference contours was related to an increase in risk of biochemical recurrence by 8–24% per mm. Conclusion: We proposed and successfully applied a novel methodology to explore the correlation between contour variation and treatment outcome. We analyzed the effect of contour deviation of the prostate CTV on biochemical recurrence for a cohort of more than 200 prostate cancer patients while taking basic clinical variables into account. Applying this methodology to a larger dataset including additional clinically important covariates and externally validating it can more robustly identify regions where contour variation directly relates to treatment outcome. For example, in the prostate case we use to demonstrate our novel methodology, external validation will help confirm or reject the counter‐intuitive results (larger contours resulting in higher risk). Ultimately, the results of this methodology could inform contouring protocols based on actual patient outcomes.
    • Novel Reviews

      Toivanen, Anna-Leena; email: anna-leena.toivanen@uef.fi; Taylor, Joanna E.; email: joanna.taylor@manchester.ac.uk (Berghahn Books, 2021-03-01)
      Michèle Rakotoson, Elle, au printemps (Saint-Maur: Sépia, 1996), 122 pp.Kathleen Jamie, Surfacing (UK: Sort of Books, 2019), 240 pp., £7.99. Kathleen Jamie (ed.), Antlers of Water: Writing on the Nature and Environment of Scotland (Edinburgh: Canongate Books, 2020), 232pp., £20.
    • Novel Rotational Combination Regimen of Skin Topicals Improves Facial Photoaging: Efficacy Demonstrated in Double-Blinded Clinical Trials and Laboratory Validation

      DiNatale, Lisa; Idkowiak-Baldys, Jolanta; Zhuang, Young; Gonzalez, Anthony; Stephens, Thomas J.; Jiang, Lily I.; Li, Weiping; Basson, Rubinder; Bayat, Ardeshir; email: ardeshir.bayat@manchester.ac.uk; email: ardeshir.bayat@uct.ac.za (Frontiers Media S.A., 2021-09-17)
      Topical antiaging products are often a first-line intervention to counter visible signs of facial photoaging, aiming for sustained cosmetic improvement. However, prolonged application of a single active topical compound was observed clinically to lead to a plateau effect in improving facial photoaging. In view of this, we set out to reduce this effect systematically using a multi-tiered approach with laboratory evidence and clinical trials. The objective of the study was to evaluate the effects of active topical ingredients applied either alone, in combination, or in a rotational manner on modulation of facial photoaging. The study methodology included in vitro, organotypic, and ex vivo skin explants; in vivo biopsy study; as well as clinical trials. We demonstrate for the first time that a pair of known antiaging ingredients applied rotationally, on human dermal fibroblasts, maximized pro-collagen I production. Indeed, rotational treatment with retinol and phytol/glycolic acid (PGA) resulted in better efficacy than application of each active ingredient alone as shown by explants and in vivo biopsy study, with penetration of active ingredients confirmed by Raman spectroscopy. Furthermore, two split-face, randomized, double-blinded clinical trials were conducted, one for 12 months to compare treated vs. untreated and the other for 6 months followed by a 2-month regression to compare treated vs. commercially marketed products. In both studies, rotational regimen showed superior results to its matching comparison as assessed by clinical grading and image analysis of crow's feet wrinkles. In conclusion, rotational regimen using retinol and PGA is effective in treating facial photoaging signs with long-lasting benefits.
    • Now, Imagine an Actually Existing Unicorn: On Russellian Worries for Modal Meinongianism

      de Jong, Andreas; email: andreas.dejong@manchester.ac.uk (Springer Netherlands, 2020-04-23)
      Abstract: Modal Meinongianism provides the semantics of sentences involving intentional verbs Priest (Towards Nonbeing, Oxford University Press, Oxford, 2016). To that end, Modal Meinongianism employs a pointed non-normal quantified modal logic model. Like earlier Meinongian views Modal Meinongianism has a characterisation principle (QCP), that claims that any condition whatsoever is satisfied by some object in some world. Recently, Everett (The nonexistent, Oxford University Press, Oxford, 2013, 169, p. 36) has proposed an argument against QCP that, if successful, gives rise to problems identical to those Russell (Mind 14:530–538, 1905, p. 533) raised for Naïve Meinongianism, namely that it allows for true contradictions, and allows us to define anything into existence. Everett claims that the ordinary meanings of “actual” license an inference pattern, such that if an object satisfies Actual A at some world, then that object satisfies A in the actual world. Given that actual world is the designated point of evaluation for truth simpliciter, QCP would fall prey to Russell’s criticisms. As opposed to Everett, I argue that, even if we grant Everett the assumption that “actual” is a modal indexical that rigidly refers to the actual world, it does not conform to the inference pattern above. This is because when an object satisfies Actual A at some world, this alters the assertoric force of “actual”, because “actual” is interpreted in the scope of some modal or intentional operator. I also explain that Everett’s proposed example carries existential commitment because the problematic noun-phrase occurs outside the scope of a modal or intentional operator.
    • Nuclear spin relaxation as a probe of zeolite acidity: a combined NMR and TPD investigation of pyridine in HZSM-5.

      Robinson, Neil; orcid: 0000-0002-0893-2190; Bräuer, Pierre; York, Andrew P E; D'Agostino, Carmine; orcid: 0000-0003-3391-8320; email: carmine.dagostino@manchester.ac.uk (2021-06-30)
      The relative surface affinities of pyridine within microporous HZSM-5 zeolites are explored using two-dimensional 1H nuclear magnetic resonance (NMR) relaxation time measurements. The dimensionless ratio of longitudinal-to-transverse nuclear spin relaxation times T1/T2 is shown to exhibit strong sensitivity to the silica/alumina ratio (SAR) of these zeolites, which is indicative of material acidity. This trend is interpreted in terms of increased pyridine surface affinity with decreasing SAR. Temperature programmed desorption (TPD) analysis corroborates this observation, revealing a distinct increase in the heat of desorption associated with adsorbed pyridine as a function of decreasing SAR. A direct correlation between NMR and TPD data suggests NMR relaxation time analysis can be a valuable tool for the non-invasive characterisation of adsorption phenomena in microporous solids.
    • Numerical Methods for Caputo–Hadamard Fractional Differential Equations with Graded and Non-Uniform Meshes

      Green, Charles Wing Ho; email: 1604518@chester.ac.uk; Liu, Yanzhi; email: 39036@llu.edu.cn; Yan, Yubin; orcid: 0000-0002-5686-5017; email: y.yan@chester.ac.uk (MDPI, 2021-10-27)
      We consider the predictor-corrector numerical methods for solving Caputo–Hadamard fractional differential equations with the graded meshes logtj=loga+logtNajNr, j=0, 1, 2, …, N with a≥1 and r≥1, where loga=logt0logt1⋯logtN=logT is a partition of [logt0, logT]. We also consider the rectangular and trapezoidal methods for solving Caputo–Hadamard fractional differential equations with the non-uniform meshes logtj=loga+logtNaj(j+1)N(N+1), j=0, 1, 2, …, N. Under the weak smoothness assumptions of the Caputo–Hadamard fractional derivative, e.g., DCHa, tαy(t)∉C1[a, T] with α∈(0, 2), the optimal convergence orders of the proposed numerical methods are obtained by choosing the suitable graded mesh ratio r≥1. The numerical examples are given to show that the numerical results are consistent with the theoretical findings.
    • Nutrition knowledge and dietary intake of hurlers

      Murphy, John; orcid: 0000-0002-8337-722X; O’Reilly, James (SAGE Publications, 2020-11-26)
      The current study investigated the association between sports nutrition knowledge and dietary quality in a sample of adult Irish male hurling players. Nutrition knowledge was measured by the validated Sports Nutrition Knowledge Questionnaire (SNKQ). Diet quality was measured by the Australian Recommended Food Score (ARFS) calculated from food frequency questionnaire data. Analysis of variance and linear modelling were used to assess associations between variables. A total of 265 (129 elite, 136 sub-elite) players were recruited. No significant difference in nutrition knowledge (SNKQ) was found between groups. Results showed a significant difference (p = 0.02; d = 0.39 ± 0.25; small) in food score (ARFS) between groups. A weak, positive association (r = 0.3, p = 0.007) was found between nutrition knowledge and food score. Elite level players, aged 28–32, with college degrees, that have previously received nutritional guidance displayed the highest levels of both nutrition knowledge and food score. Higher levels of nutrition knowledge and food score were expected in elite players, however were only found in food score. Nutrition knowledge does contribute to dietary quality although future interventions should focus on specific gaps in knowledge such as how to meet total energy/carbohydrate requirements.
    • Nutritional parameters and outcomes in patients admitted to intensive care with COVID-19: a retrospective single-centre service evaluation

      Eden, Timothy; McAuliffe, Shane; orcid: 0000-0002-7166-4299; Crocombe, Dominic; Neville, Jonathan; Ray, Sumantra (BMJ Publishing Group, 2021-08-05)
      Background: COVID-19 is an inflammatory syndrome caused by novel coronavirus SARS-CoV-2. Symptoms range from mild infection to severe acute respiratory distress syndrome (ARDS) requiring ventilation and intensive care. At the time of data collection, UK cases were around 300 000 with a fatality rate of 13% necessitating over 10 000 critical care admissions; now there have been over 4 million cases. Nutrition is important to immune function and influences metabolic risk factors such as obesity and glycaemic control, as well as recovery from acute illnesses. Poor nutritional status is associated with worse outcomes in ARDS and viral infections, yet limited research has assessed pre-morbid nutritional status and outcomes in patients critically unwell with COVID-19. Objectives: Investigate the effect of body mass index (BMI), glycaemic control and vitamin D status on outcomes in adult patients with COVID-19 admitted to an intensive care unit (ICU). Methods: Retrospective review of all patients admitted to a central London ICU between March and May 2020 with confirmed COVID-19. Electronic patient records data were analysed for patient demographics; comorbidities; admission BMI; and serum vitamin D, zinc, selenium and haemoglobin A1c (HbA1c) concentrations. Serum vitamin D and HbA1c were measured on admission, or within 1 month of admission to ICU. Primary outcome of interest was mortality. Secondary outcomes included time intubated, ICU stay duration and ICU-related morbidity. Results: Seventy-two patients; 54 (75%) men, mean age 57.1 (±9.8) years, were included. Overall, mortality was 24 (33%). No significant association with mortality was observed across BMI categories. In the survival arm admission, HbA1c (mmol/mol) was lower, 50.2 vs 60.8, but this was not statistically significant. Vitamin D status did not significantly associate with mortality (p=0.131). However, 32% of patients with low vitamin D (<25 IU/L) died, compared with 13% of patients with vitamin D levels >26 IU/L. Serum zinc and selenium, and vitamin B12 and folate levels were measured in 46% and 26% of patients, respectively. Discussion/conclusion: Increased adiposity and deranged glucose homeostasis may potentially increase risk of COVID-19 infection and severity, possibly relating to impaired lung and metabolic function, increased proinflammatory and prothrombotic mechanisms. Vitamin D deficiency may also associate with poorer outcomes and mortality, supporting a possible role of vitamin D in immune function specific to pulmonary inflammation and COVID-19 pathophysiology. There are plausible associations between raised BMI, glycaemic control, vitamin D status and poor prognosis, as seen in wider studies; however, in this service evaluation audit during the first wave of the pandemic in the UK, with a limited data set available for this analysis, the associations did not reach statistical significance. Further research is needed into specific nutritional markers influencing critical care admissions with COVID-19.
    • Nutritional parameters and outcomes in patients admitted to intensive care with COVID-19: a retrospective single-centre service evaluation

      Eden, Timothy; McAuliffe, Shane; orcid: 0000-0002-7166-4299; Crocombe, Dominic; Neville, Jonathan; Ray, Sumantra (BMJ Publishing Group, 2021-08-05)
      Background: COVID-19 is an inflammatory syndrome caused by novel coronavirus SARS-CoV-2. Symptoms range from mild infection to severe acute respiratory distress syndrome (ARDS) requiring ventilation and intensive care. At the time of data collection, UK cases were around 300 000 with a fatality rate of 13% necessitating over 10 000 critical care admissions; now there have been over 4 million cases. Nutrition is important to immune function and influences metabolic risk factors such as obesity and glycaemic control, as well as recovery from acute illnesses. Poor nutritional status is associated with worse outcomes in ARDS and viral infections, yet limited research has assessed pre-morbid nutritional status and outcomes in patients critically unwell with COVID-19. Objectives: Investigate the effect of body mass index (BMI), glycaemic control and vitamin D status on outcomes in adult patients with COVID-19 admitted to an intensive care unit (ICU). Methods: Retrospective review of all patients admitted to a central London ICU between March and May 2020 with confirmed COVID-19. Electronic patient records data were analysed for patient demographics; comorbidities; admission BMI; and serum vitamin D, zinc, selenium and haemoglobin A1c (HbA1c) concentrations. Serum vitamin D and HbA1c were measured on admission, or within 1 month of admission to ICU. Primary outcome of interest was mortality. Secondary outcomes included time intubated, ICU stay duration and ICU-related morbidity. Results: Seventy-two patients; 54 (75%) men, mean age 57.1 (±9.8) years, were included. Overall, mortality was 24 (33%). No significant association with mortality was observed across BMI categories. In the survival arm admission, HbA1c (mmol/mol) was lower, 50.2 vs 60.8, but this was not statistically significant. Vitamin D status did not significantly associate with mortality (p=0.131). However, 32% of patients with low vitamin D (<25 IU/L) died, compared with 13% of patients with vitamin D levels >26 IU/L. Serum zinc and selenium, and vitamin B12 and folate levels were measured in 46% and 26% of patients, respectively. Discussion/conclusion: Increased adiposity and deranged glucose homeostasis may potentially increase risk of COVID-19 infection and severity, possibly relating to impaired lung and metabolic function, increased proinflammatory and prothrombotic mechanisms. Vitamin D deficiency may also associate with poorer outcomes and mortality, supporting a possible role of vitamin D in immune function specific to pulmonary inflammation and COVID-19 pathophysiology. There are plausible associations between raised BMI, glycaemic control, vitamin D status and poor prognosis, as seen in wider studies; however, in this service evaluation audit during the first wave of the pandemic in the UK, with a limited data set available for this analysis, the associations did not reach statistical significance. Further research is needed into specific nutritional markers influencing critical care admissions with COVID-19.
    • Occlusion: is there a third way? A discussion paper.

      Davies, Stephen; email: stephen.j.davies@manchester.ac.uk; Dawson, Philip; Weerapperuma, Indika; Waring, David; Beddis, Hannah; Leven, Johanna; Aminian, Amin; Rayarel, Ashish; Cowan, Callum; Crawford, Charles; et al. (2021-08-13)
      This paper does not set out to describe the reasons why a new concept of dental care should be deemed as acceptable and recognised as mainstream. Rather, the starting point of this paper is the belief that some dentists who are increasing the overall vertical dimension for worn dentition patients are not using the protocols of the traditional 're-organised approach'. If adhesive direct restorations are used, there seems to be anecdotal indication that despite not restoring in the terminal hinge axis, it can have a successful outcome.So, while not criticising this approach simply because it does not follow orthodoxy, the paper has two objectives. It hopes to stimulate some debate and research on this subject. Furthermore, by suggesting some parameters for what might be considered a new approach, it aims to improve patient outcome. [Abstract copyright: © 2021. The Author(s), under exclusive licence to the British Dental Association.]
    • Off the couch: a psychiatrist’s candid stories of hope and healing

      Loewenthal, Kate Miriam; orcid: 0000-0001-7667-7809 (Informa UK Limited, 2021-07-09)