Senior Research Fellow Research Articles

1150-P: A Hyperhomocysteinemia-Inducing Diet Alters Gut Microbiome and Glucose Homeostasis

Hyperhomocysteinemia (HHcy) is a risk factor for higher mortality in type 2 diabetic patients. A high methionine low folate (HMLF) diet chronically induces HHcy by causing homocysteine (Hcy) accumulation in systemic circulation. A higher systemic Hcy level is clinically associated with the incidence of diabetes mellitus. However, whether HHcy negatively impacts on glucose metabolism and insulin sensitivity remains inconclusive and contradictory. Meanwhile, very few studies have focused on the direct impact of HMLF diet on glucose homeostasis, and that on the gut flora. To understand the impact of HMLF diet, C57BL/6 mice were fed a HMLF diet for 8 consecutive weeks. HMLF diet feeding successfully induced HHcy, caused progressive body weight loss, and slightly impaired glucose homeostasis, as revealed by slight glucose intolerance and insulin resistance, in C57BL/6 mice. Of noted, HMLF diet feeding altered the gut microbiome profile that the relative abundance of porphyromonadaceae family of bacteria was enriched in diet-induced HHcy mice. Interestingly, a previous study correlated the higher frequency of porphyromonadaceae with the development of GLP-1 resistance, implying that HMLF diet might prompt the development of GLP-1 resistance. GLP-1 resistance results in the impairment on glucose-induced insulin secretion. These results provide novel insights into the roles of impaired glucose homeostasis and gut microbiome in the pathogenesis of HHcy-related complications. In short, an improper dietary pattern might impair glucose homeostasis by altering the gut microbiome profile. Disclosure C. Cheng: None. C. Wang: None. Y. Huang: None. Funding Chinese University of Hong Kong (4930709); Hong Kong Research Grants Council Senior Research Fellow Scheme 2020/21 (SRFS2021-4S04)

Understanding micronutrient bioavailability and the impact on micronutrient malnutrition

Jayashree Arcot received her Bachelor's degree in Nutrition and Dietetics from the University of Madras, India and a Master's degree in Food Science and Nutrition. She received her PhD in Foods and Nutrition from the Andhra Pradesh Agricultural University in Hyderabad, India in 1988 while being a recipient of the prestigious Senior Research Fellowship from the Indian Council of Agricultural Research. While in Hyderabad she had the opportunity to collaborate with several leading scientists in the field of nutrition at the National Institute of Nutrition, a premier organization under the auspices of the Indian Council of Medical Research in India and the International Crops Research Institute for Semi-arid Tropics (ICRISAT). She mastered the analysis of vitamins in foods using the microbiological assay during her PhD. When she arrived in Australia in the early 1990s, as an academic at the University of New South Wales, Sydney, she had the opportunity to establish a research group in the field of food science and nutrition. She pursued several projects funded by government and industry with her food-based approaches to solve nutrition problems particularly micronutrient malnutrition. Fascinated by the complexity of vitamins in foods and their matrix effects, she established a laboratory for vitamin methodology for foods using the microbiological assay, high-end chromatography (LC-MS/MS), to measure different forms of vitamins, for example, folates; studying vitamin bioavailability in humans. Her lab was the first in the Oceania region capable of measuring vitamins in foods using the microbiological assay. She has conducted several international workshops and short courses in food composition and vitamin assays for researchers. She has pursued her interest in vitamins through several fortification projects and bioavailability of folate-fortified foods in humans and in vitro cell culture techniques. Her other interests are in developing accurate methods for the bioactive compounds in foods and studying their bioactivity using cell culture techniques. She has several publications in the field of 2D culture models for the bioaccessibility and bioavailability of compounds such as phenolic acids, flavonoids, and carotenes from foods. Her publications in this field are related to interactions between these bioactive compounds in foods and their health properties such as cellular anti-inflammatory and anti-oxidant effects. More recently, she has focused on food and health security with a particular focus on complementary feeding in infants, and malnutrition in middle-income and lower income countries. In this context, she has been studying ways of recovering nutrients (protein) from food manufacturing stream wastes and collaborated with industry on several projects. She has over 100 research publications and has graduated several research students in the last 20 years. She is a professional member of the Australian Institute of Food Science and Technology, Nutrition Society of Australia, and the American Society of Nutrition. She is an Associate Professor of Food and Health at the School of Chemical Engineering, UNSW, Sydney, Australia.

TO THE 85TH ANNIVERSARY FROM BIRTHDAY DOCTOR OF AGRICULTURAL SCIENCE PROFESSOR BORYS YEVHENOVYCH PODOBA BORYS YEVHENOVYCH PODOBA – A RECOGNIZED AUTHORITY ON AGRICULTURAL ANIMAL GENETIC

Borys Yevhenovych Podoba, a well-known scientist, chief researcher of the laboratory of information systems of the Institute of Animal Breeding and Genetics nd. a.M.V.Zubets of NAAS is celebrating his 85th birthday.
 Borys Podoba was born on April 28, 1936 in Chernigov. In 1959 he graduated from the agronomic faculty of the Ukrainian Academy of Agricultural Sciences. In 1959–1968 he worked at the Ukrainian Research Institute of Poultry, where in 1966 he defended his Ph. D. thesis on the topic "The use of heterosis in duck breeding."
 In 1968 he began working at the Scientific Research Institute of Animal Husbandry of the Forest-Steppe and Polesye of the Ukrainian SSR, where he worked as a senior researcher, and since 1976 – as the head of the laboratory of genetics. In 1976 he was awarded the academic title of senior research fellow with a degree in breeding and selection of farm animals. Since 1978, B. Ye. Podoba has been working at the Institute of Animal Breeding and Genetics as a senior researcher, then as head of the laboratory for the genetic foundations of breeding. In 1997 he defended his doctoral dissertation "The use of polymorphism of erythrocyte antigens for assessing breeding resources, increasing the genetic potential and preserving the gene pool of cattle", by the specialty "genetics".
 Borys Yevhenovych Podoba developed the theory and methods of using blood groups in the genetic monitoring system when creating and improving breeds, preserving biodiversity in animal husbandry in Ukraine, and made a significant contribution to the organization and improvement of the immunogenetic service of Ukraine. One of the directions of his scientific work was the combination of immunogenetic methods with breeding aspects of the individual development of animals. This work connects the generations of breeders G. F. Podoba on the methodological approaches of selection breeding of breeding young cattle used in the creation of a herd of Mining Schwyz, and E. G. Podoba on the principles of selection to improve the efficiency of feed use by farm animals.
 All years of scientific activity, B. Ye. Podoba has been an active member, first of the All-Union and then the Ukrainian Society of Geneticists and Breeders nd. a. N. I. Vavilov. In 2015 he received the title of degree professor in genetics.
 The results of B. Ye. Podoba's scientific research are presented in more than 300 scientific works published by him, including 9 monographs, 11 scientific articles in foreign publications, more than 20 recommendations and breeding programs, 7 patents and copyright certificates on genetics, selection, breeding, preservation of the genepool and biodiversity of farm animals, which have become a significant contribution to the treasury of Ukrainian science.
 The staff of the Institute congratulates the esteemed professor Borys Yevhenovych Podoba and wishes him good health and creative longevity!

Simulated heterogeneity in purkinje-ventricular electrophysiology following acute myocardial infarction remodelling

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Wellcome Trust Senior Research Fellowship in Basic Biomedical Sciences Background Coronary heart disease is a common substrate for sudden cardiac death. Several clinical and experimental studies on ischemic heart diseases have highlighted the involvement of the His-Purkinje system in the initiation and maintenance of ventricular arrhythmias. Biophysically-detailed mathematical models and computational multiscale simulations can help in gather insights of the cellular and tissue mechanisms underlying the trigger and maintenance of arrhythmias. Purpose The goal of this study is to evaluate the effects of ionic remodelling on human Purkinje and ventricular cells in the acute stage post myocardial infarction. Methods Two recently published computational models were used to represent the electrophysiology of cardiac Purkinje and ventricular cells, including transmural heterogeneity (endo, mid, epi myocytes). Cardiac ionic remodelling was observed at the border zone of the infarcted region, mostly in canine and porcine models. For both ventricular and Purkinje models, remodelling was implemented as a variation of the number of function channels, i.e., of the current conductance for Na+, Ca2+ and K+ currents. Simulations were performed for both models at different pacing frequencies (cycle length from 400 to 1000 ms) to assess a set of action potential (AP) biomarkers and AP rate-dependence at fast pacing. Early afterdepolarisation (EADs) were induced at slow pacing under hERG block. Results Figure 1 reports the results for the ventricular (A) and Purkinje (B) electrophysiology for the healthy (blue) and post-infarction (red) tissues at 1 Hz (left), at different frequencies (middle) and under 85% hERG block at 0.25 Hz (right). At 1 Hz, ionic remodelling reduced the AP depolarisation rate, abolished the AP notch and led to AP prolongation for both models. Purkinje AP showed also elevated resting membrane potentials and increased diastolic depolarisation. The mid-cardiomyocyte and Purkinje models showed a small increase in the APD- rate dependence slope. Ionic remodelling did not affect significantly the EAD dynamics in the ventricular model, apart from further delaying the AP repolarisation. In the Purkinje model, ionic remodelling led to automaticity and changed the EAD dynamics, which disappeared from the paced AP but occurred after the spontaneous AP. Conclusion In this study we investigated the effects of ionic current remodelling in ventricular and Purkinje cells following acute myocardial infarction. Results showed that remodelling at the border zone increased the heterogeneity between Purkinje and ventricular cells. A further step into the investigation of pro-arrhythmic mechanisms induced by myocardial infarction will be to perform multiscale simulations at whole organ level in 3D anatomical models of human ventricles, including the His-Purkinje system. Abstract Figure 1

Computational investigation of drug-induced effects on human cardiac electro-mechanics

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NC3Rs Infrastructure for Impart Award (NC/P001076/1) Wellcome Trust Senior Research Fellowship in Basic Biomedical Sciences (214290/Z/18/Z) Background Human-based computer modelling and simulations have been widely used in cardiac electrophysiology, to provide a better understanding of the ionic mechanisms underlying risk of arrhythmias, and their modulation by drugs and diseased conditions. More recently, multiscale computer models of human cardiac electro-mechanics have been developed. These models provide the means for a comprehensive investigation of action potential, calcium transient, active force, and their variability in the population, and can predict drug-induced contractility changes in humans. Purpose This study aims to perform a computational investigation of variability in human cardiac contractility biomarkers and their modulation by well-known drugs. Methods We considered the most recent model of human ventricular electro-mechanics (Margara et al. 2020). We constructed a population of 300 cells by randomly varying the main ionic currents in the model, to represent the biological variability observed in human experimental data. We then simulated the effect of 10 reference compounds, 6 of which with known pro-arrhythmic risk. Simulations were performed at 1 Hz for multiple drug concentrations, using the Virtual Assay software. A set of action potential, calcium transient and active force biomarkers were computed, as well as the electro-mechanical window, and the occurrence of early after-depolarisations and after-contractions in the virtual population. Simulation results were compared against clinical risk of drug-induced arrhythmias and experimental recording from human ventricular myocytes from literature. Results Overall, biomarker variability in the virtual population increased following drug application compared to control conditions. All compounds had a negative inotropic effect in simulation, with a marked decrease of the active tension peak, e.g. -80% for nifedipine 8 nM. This is in agreement with human experimental data for all compounds except Dofetilide, for which no inotropic effect was observed in vitro. Compounds with known risk of arrhythmias provoked early after-depolarisations, which in turn caused after-contractions. Their occurrence in the population increased together with the drug concentration, e.g. 3.6% at 0.16 µM and 48% at 0.48 µM for droperidol. In addition, these compounds also displayed prolonged action potential and calcium transient, and a shortening of the electro-mechanical window, all known biomarkers of pro-arrhythmia. Conclusions We evaluated the effect and the cardiac safety of 10 reference compounds in a population of 300 human ventricular electro-mechanical models. Simulation results were in good agreement with experimental data in human ventricular cardiomyocytes, and they allowed to identify the compounds with a known pro-arrhythmic risk based on drug-induced early after-depolarisations and after-contractions. This methodology provides new insights into variability in human cardiac contractility and its modulation by drugs.

Defining a role for AI ethics in national security

We spoke with Mariarosaria Taddeo, an associate professor and senior research fellow at the Oxford Internet Institute and Dstl Ethics Fellow at the Alan Turing Institute working on digital and AI ethics about two recent reports from the UK and the US on using AI in national defence and security.

A Brief History of the Anaerobic Threshold Concept

Aamer Sandoo, B.Sc., M.Sc., Ph.D.,is a senior lecturer in Cardiovascular Physiology at Bangor University, UK, and senior research fellow in the National Health Service. Dr. Sandoo’s research examines the intricate biological mechanisms that predispose certain clinical populations to cardiovascular disease. He is a renowned expert in assessments of noninvasive blood vessel function and has authored more than 45 scientific articles and presented at 24 conferences. He is passionate about teaching students of all ages about the physiological importance of exercise and advocates the concept that “exercise is medicine.” Dr. Sandoo also freely provides educational content on his popular YouTube channel, “Physiology Made Easy” (https://www.youtube.com/channel/UCxfslQe8hBQ3fSrC31HcZDw). In his spare time, Dr. Sandoo takes part in several sporting activities, including boxing, running, weightlifting, hiking, and motorcycling.

An interview with Professor Gregory Steinberg, Co-Director of the Centre for Metabolism, Obesity and Diabetes Research and the Canada Research Chair in Metabolism and Obesity at McMaster University

Gregory Steinberg completed his PhD at the University of Guelph, Canada, where he studied the role of leptin in muscle in the laboratory of Professor David Dyck. From 2002 to 2006, Greg was a postdoctoral fellow with Professor Bruce Kemp at St Vincent’s Institute of Medical Research, Australia, where he studied the role of the AMP-activated protein kinase (AMPK). In 2006, he started his academic career as Lecturer, Senior Research Fellow and Head of Metabolism at St Vincent’s Institute and the University of Melbourne. He returned to Canada in 2009 where his research studies cellular energy sensing mechanisms and looks at how endocrine factors, lipid metabolism and insulin sensitivity are linked and contribute to the development of obesity, type 2 diabetes, cardiovascular disease and cancer. He is the recipient of numerous awards, including the Diabetes Canada-Canadian Institutes of Health Research, Diabetes Young Scientist Award; the Endocrine Society Richard E Weitzman Outstanding Early Career Investigator Award; the Canadian Institutes of Health Research Gold Leaf Prize; and the American Diabetes Association Outstanding Scientific Achievement Award. To help celebrate the 100th anniversary of the discovery of insulin, Greg also recently took part in Diabetes Canada’s fitness fundraiser, ‘Lace Up for Diabetes’, riding 8000 km (the equivalent of crossing Canada) over a period of 80 days and raising almost $15,000 to help fund the next breakthrough discovery in the field. Coinciding with our issue theme of diabetes, which also marks the centenary of this discovery by Canadian scientists, The Biochemist spoke to Greg briefly about his work in this area.

Women in Science Portrait – Dr. Margit Fábián

Dr. Margit Fabian is one of the leading figures among the new breed of talents working at the Budapest Neutron Centre. As a senior research fellow, she is the nuclear waste management team lead at ...

VIEWS AND PERSPECTIVES OF HYPERTENSION EXPERTS IN GREECE REGARDING THE EFFICACY AND SAFETY OR RENAL SYMPATHETIC DENERVATION

Objective: The role of renal sympathetic denervation (RSD) in the management of arterial hypertension remains controversial, given the initial enthusiasm by the first studies, the great disappointment by the first sham-controlled randomized study and the current promising finding in recent randomized trials. Therefore, an uncertainty exists about the beliefs of hypertension specialists regarding RSD. This analysis presents the opinions of hypertension experts in Greece regarding the efficacy and safety of RSD. Design and method: Chairpersons of ESH Hypertension Excellence Centers in Greece and their senior clinical research fellows, were invited to participate in a meeting aiming to discuss the current evidence on the clinical utility of RSD. Individual responses were recorded and qualitatively analyzed, in order to reach consensus about the safety and efficacy of RSD. Results: Twenty-five experts participated in the meeting (cardiologists 52%, internists 40%, nephrologists 8%). Participants agreed upon the favorable results of three recent clinical trials and supported the view that RSD is an effective method. 44% believe that further technological development of the denervation catheter is expected to improve the results of the technique. Importantly, 22% of the experts highlighted the additional benefits of the method in regressing target organ damage and in patients with increased activity of the sympathetic nervous system. However, 44% of the experts underlined the lack of reliable predictive markers for the efficacy of RSD, while 32% highlighted the lack of long-term efficacy studies. Experts universally agreed on the safety of the method. However, 64% stated that the duration of the RSD trials was short, and thus there is lack of data on the long-term safety of RDS. Of note, 76% considered the method as easy to perform and minimally invasive. Conclusions: The majority of the hypertension experts in Greece agree upon the efficacy of RSD and all had minimal concerns of the safety of method. More data are needed to reveal the degree of confidence among hypertension experts regarding the efficacy and the safety of the whole procedure and its specific aspects.

HYPERTENSIVE PATIENTS AS CANDIDATES FOR RENAL SYMPATHETIC DENERVATION: CONSENSUS OPINION OF HYPERTENSION EXPERTS IN GREECE

Objective: Several studies have evaluated the efficacy and safety of renal sympathetic denervation (RSD) in patients with hypertension and other conditions characterized by sympathetic overactivity. However, to date there is no consensus in the literature about which patients are the most appropriate candidates for RSD. This analysis presents the opinions of hypertension experts in Greece regarding potential candidates for RSD. Design and method: Chairpersons of ESH Hypertension Excellence Centers in Greece and their senior clinical research fellows, were invited to participate in a meeting aiming to discuss the current evidence on the clinical utility of RSD. Individual responses were recorded and qualitatively analyzed, in order to reach consensus about potential RSD candidates. Results: Twenty-five experts participated in the meeting (cardiologists 52%, internists 40%, nephrologists 8%). (i) 84% of the experts agreed that patients with resistant or uncontrolled hypertension are the most eligible candidates for RSD. (ii) Patients who are either non-adherent to treatment (72%) or discontinued antihypertensive drugs due to adverse events (64%) were suggested as potential candidates. (iii) Patients with severe left ventricular hypertrophy or other TOD were also proposed as potential candidates (24%). (iv) Individuals with diseases associated with sympathetic overactivity (72%), such as obstructive sleep-apnea syndrome, chronic kidney disease, heart failure, arrhythmias, and polycystic ovary syndrome. (v) Patients at the initial stages of hypertension (12%), women of child-bearing potential (4%), drug naïve patients (16%), and patients of young age without TOD were also considered (12%). (vi) Hypertensive patients with increased sympathetic activity, such as patients with excessive white-coat hypertension or sodium sensitivity, were also proposed as potential candidates (8%). (vii) Patients preferring RSD over life-long drug treatment might also be eligible (24%). Conclusions: Seven patient groups were identified as potential candidates for RSD. Experts agreed on the eligibility of patients with resistant hypertension, yet other groups of patients were also proposed. More data are needed to properly identify those patients who will benefit the most from RSD, aiming towards personalized therapy in this field.

The Impact of Prioritisation and Dosing Intervals on the Effects of COVID-19 Vaccination in Europe: An Agent-Based Cohort Model

Background: Different strategies are being explored to maximise the effect of COVID-19 vaccination in Europe. We studied the impact of different population prioritisation and dose intervals on infections, hospitalisations, mortality, and public health restrictions.Method: An agent-based model was built to quantify the impact of different vaccination strategies over 6 months. Input parameters were derived from recent phase 3 trials and official European figures. We explored the prioritisation of vulnerable people, care-home staff and residents, and contagious groups and dose intervals from 3 to 12 weeks.Findings: Prioritising vulnerable people, rather than the most contagious groups, led to higher COVID-19 prevalence, but clear reductions in mortality, hospital admissions, and restrictions. At a realistic vaccination speed of ≤0·1% population/day, separating doses by 12 (instead of 3) weeks reduced hospitalisations, mortality, and restrictions for vaccines with similar first- and second-dose efficacy (e.g., the Oxford-AstraZeneca and Moderna vaccines), but not for those with lower first-dose efficacy (e.g., the Pfizer/BioNTech vaccine).Interpretation: Mass vaccination should dramatically reduce the effect of COVID-19 on Europe’s health and economy. Early vaccination of vulnerable populations will reduce mortality, hospitalisations, and public health restrictions compared to prioritisation of the most contagious groups. The choice of interval between doses should be based on expected vaccine availability and first-dose efficacy, with 12-week intervals preferred over shorter intervals in most realistic scenarios.Funding Statement: The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). DPA is funded through a NIHR Senior Research Fellowship (Grant number SRF-2018-11-ST2-004). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the department of Health. CP research is partially funded by Ministerio de Ciencia e Innovación, Gobierno de España through the grant PGC2018-095456-B-I00. MC is funded by La Caixa Foundation (ID 100010434), under agreement LCF/PR/GN17/50300003.Declaration of Interests: Dr. Prats reports grants from Ministerio de Ciencia e Innovación, Gobierno de España (PGC2018-095456-B-I00), during the conduct of the study; other from European Commission, DG-CONNECT (CNECT/LUX/2020/LVP/0085, LC-01591965), outside the submitted work. Dr. Prieto-Alhambra reports grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work; and HTA Funding Committee membership. Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department and open for external participants. Dr. CATALÀ reports grants from Ministerio de Ciencia e Innovación, Gobierno de España (PGC2018-095456-B- I00), grants from La Caixa Foundation (ID 100010434), under agreement LCF/PR/GN17/50300003, during the conduct of the study; other from European Commission, DG-CONNECT (CNECT/LUX/2020/LVP/0085, LC-01591965), outside the submitted work. Ms. Li has nothing to disclose.Ethics Approval Statement: Only public aggregated data was used for this study. The use of such data does not require ethics approval.

First person – Pragya Chandrakar

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Pragya Chandrakar is first author on ‘Jagged–Notch-mediated divergence of immune cell crosstalk maintains the anti-inflammatory response in visceral leishmaniasis’, published in JCS. Pragya conducted the research described in this article while a Senior Research Fellow in Dr Susanta Kar's lab at the CSIR Central Drug Research Institute, Lucknow, India. She is now a Postdoctoral Research Fellow in the lab of Dr John Chan at Albert Einstein College of Medicine, New York, USA, investigating the different possible mechanisms by which foreign pathogens breach the immune system.

Notes on Contributors

Notes on Contributors

Labour's post‐Brexit electoral strategy

Labour's <scp>post‐Brexit</scp> electoral strategy

Robust and Prototypical Immune Responses Towards Influenza Vaccines in the High-Risk Group of Indigenous Australians

Background: Morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in high-risk groups, including Indigenous people globally. Although vaccination against influenza is recommended for those most at risk, studies on immune responses elicited by seasonal vaccines in Indigenous populations are largely missing, with no data available for Indigenous Australians and only one report published on antibody responses in Indigenous Canadians. Methods: We recruited 78 Indigenous and 84 non-Indigenous Australians vaccinated with the quadrivalent influenza vaccine into the LIFT-V cohort, and collected blood to define baseline, early (day 7) and memory (day 28) immune responses. We performed in-depth analyses of T and B cell activation, formation of memory B cells and antibody profiles, and investigated host factors that could contribute to vaccine responses. Findings:We found robust antibody responses to influenza vaccination induced in Indigenous Australians, with activation profiles of circulating T follicular helper type-1 (cT FH 1) cells at the acute response strongly correlating with total change of antibody vaccine titres induced by vaccination. Formation of influenza-specific haemagglutinin (HA)-binding memory B cells was significantly higher in seroconverters compared to non-seroconverters. Back-boosting of antibodies towards previously circulating influenza strains was observed following influenza vaccination. In-depth antibody characterisation revealed a reduction in IgG3 pre- and post-vaccination in the Indigenous Australian population, potentially linked to the increased frequency of G3m21* allotype. Interpretation: Overall, our data provide the first evidence that Indigenous populations elicit robust, broad and prototypical immune responses following immunisation with seasonal inactivated influenza vaccines. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and its subsequent complications. Funding: This work was funded by the Australian National Health and Medical Research Council (NHMRC) Program Grant (#1071916) to KK, NHMRC Project Grant (#1122524) to KK, ST, AM, NHMRC Project Grant (#1141840) to MP, KLF, Clifford Craig Foundation Grant (#145) to KLF, and NHMRC Investigator Grant (#1173871) to KK supported this work. EBC is a NHMRC Peter Doherty Fellow. ST is a NHMRC Career Development Fellow (#1145033). This work is supported by the NHMRC program grant 111 #1149990 (SJK), NHMRC project grant #1162760 (AKW). KK is supported by a NHMRC Senior Research Fellowship (#1102792) and SJK by a NHMRC Senior Principal Research Fellowship (#1136322). LH is supported by the Melbourne International Research Scholarship the Melbourne International Fee Remission Scholarship from The University of Melbourne. CES has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 792532. The Melbourne WHO Collaborating Centre for Reference Research on Influenza is supported by the Australian Government Department of Health. Declaration of Interest: None to declare. Ethical Approval: All experiments were conducted according to the Declaration of Helsinki principles and NHMRC Code of practice and approved by the University of Melbourne Human Research Ethics Committee (#1955465 and #1441452), the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (#2012-1928), and the Tasmanian Human Research Ethics Committee (#H0015460).

Acetaminophen (Paracetamol), COVID-19, and Misleading Conclusions: A Commentary.

Dr. Shader is Founding Editor-in-Chief Emeritus of the Journal of Clinical Psychopharmacology. He is currently Senior Research Fellow and Medical Consultant at the Tufts Center for the Study of Drug Development and Professor Emeritus in the Departments of Immunology and Psychiatry at the Tufts University School of Medicine, Boston, Massachusetts. Received November 20, 2020; accepted after revision December 8, 2020. Reprints: Richard I. Shader, MD, Tufts University School of Medicine, 75 Kneeland St, Boston, MA 02111, USA (e-mail: [email protected]).

Peer review declaration

All papers published in this volume of IOP Conference Series: Earth and Environmental Science have been peer reviewed through processes administered by the Editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal published by IOP Publishing.• Type of peer review: Single-blind • Conference submission management system: a two-stage selection system (that included consideration of preliminary materials at the first stage and full-length materials at the second stage) was organized on the basis of the conference website(http://irigs.irk.ru/northeastasia2020/). Communication with the authors was conducted via e-mail. • Number of submissions received: 348 • Number of submissions sent for review: 120 • Number of submissions accepted: 91 • Acceptance Rate (Number of Submissions Accepted / Number of Submissions Received X 100): 26.0% • Average number of reviews per paper: 1.71 • Total number of reviewers involved: 106 • Any additional info on review process: The article selection process took place in two stages. At the first stage, one-page materials were evaluated by incoming editors and reviewers. Some authors were invited to participate in the conference based on these reviews, and some of them had the opportunity to send full-length materials. At the second stage, reviewers evaluated full-length articles, the best of which were selected for publication in the collection based on the results of the conference. • Contact person for queries: (please include name, affiliation and email address) Myadzelets Anastasia, Conference secretary, Senior research fellow, Dr. Sci. (Geogr.), igsbras.conf@gmail.com

Platform: In Theory

Platform: In Theory Gerhard Maré (bio) and Peter Vale (bio) As regular readers of this journal you will know that Platform: In Theory was launched in Transformation 104. On that occasion, we made an introductory argument for the deliberate exploration and employment of theory and also the implications of the absence the clear relevance and application of theory for our understanding of the social world. What would we like to see happening, through contributions, in this section in future editions of the journal? The first, is self-reflection: in the previous issue we suggested that the ‘rich tradition of theorising on (and around) public discourse and public policy’, in South Africa, ‘has still to be fully explored’ (which would include recognising important individuals, fields of theory development, published work, and university courses and departments, and the part theoretical contestation played – and plays – in intellectual, organisational practice and policy formulation). The second is recovery: as Transformation has regularly editorially noted (#1 (1986), #38 (1999), #50 (2002), #75 (2011), #90 (2016), #100 (2019)), we remain interested in critique and the ‘critical’ exploration of the social, of explaining social concerns, of exposing and engaging with theories which ‘underlie systems of domination, exploitation and oppression’; but also theories which will assist in shaping engagement with transforming such a state of affairs. This sense of critical engagement will shape our selection of submissions for this regular section in the journal – Platform: In Theory. This is not to imply that there is a single position – such an absurdity would go against notions of complexity, nuance and articulation. The third is the exploration of new arenas: so, the next issue (Transformation 106) will carry an article on the notion of ‘keywords’, first expressed in the now famous book Keywords: a vocabulary of culture and society (published in 1976, by Fontana in their ‘Communications Series’), in which ‘Theory’ is but one word which is subjected to deep analysis. [End Page 116] The approach has since been adopted and adapted many times, also in publications in South Africa. The article will serve to launch an on-going project through Platform: In Theory, soliciting contributions on what are argued to be words key to understanding this region and its place globally, and – importantly – to changing it. And, of course, we will welcome contributions to this platform, including debate and comment on what appears here, and to wider issues. It is to serve as a Platform, after all. [End Page 117] Gerhard Maré Gerhard Maré is an emeritus professor at the University of KwaZulu-Natal. His 2020 book is Ethnic Continuities and a State of Exception: Goodwill Zwelithini, Mangosuthu Buthelezi and Jacob Zuma. Peter Vale Peter Vale is Senior Research Fellow, Centre for the Advancement of Scholarship, University of Pretoria. Recently he has published a chapter on cartoons and Afrikaner Nationalism; a book (with Vineet Thakur) on the Johannesburg origins of International Relations; and contributed to an Oxford Handbook on ‘South Africa and the idea of peaceful change’. pgmare@gmail.com petercjvale@gmail.com Copyright © 2021 Transformation: Critical Perspectives on Southern Africa

The Russian State and Russian Energy Companies, 1992–2018

Martin Kragh, Deputy Director of the Stockholm Centre for Eastern European Studies (SCEEUS) and Senior Research Fellow at the Swedish Institute of International Affairs, reviews Ingerid M. Opdahl's book, The Russian State and Russian Energy Companies, 1992–2018 (Routledge, 2020).