Philippa Kaur

The rise of animals (metazoans) is a seminal event in the history of life. The Cambrian Radiation ~540 Ma marks the appearance of abundant and diverse metazoans and increasing ecosystem complexity in the fossil record1. A causal relationship between the redox and fossil records is proposed, where oxygen provision reached a threshold, or series of thresholds, which allowed for the diversification of metazoans with increasing metabolic demands2. Global geochemical data, however, suggest that oxygenation was not a simple, linear process, but rather occurred episodically via a series of short-lived pulses (1–3 Myr), or ‘oceanic oxygenation events’ (OOEs)3,4. Early and even later Cambrian seas likely had shallower, and more dynamic, oxygen minimum zones (OMZs) than modern oceans5,6. Such pulses of increased oxygenation (and related changes in productivity) are hypothesised to have increased the extent of shallow-ocean oxygenation and hence to have promoted diversification7. But what remains unquantified is the community-wide response of metazoans to such redox cycles, an insight into the evolutionary processes involved, and hence whether these pulses were indeed a driving force for the Cambrian Radiation.In order to test the hypothesis that oxic pulses led to diversification and potentially ecological development, a correlation between increased oxygenation, rates of origination, and metrics of metazoan ecosystem complexity needs to be demonstrated. Early Cambrian marine environments were heterogeneous with respect to oxygen provision and nutrient load at a regional scale, so in order to investigate potential correlations, we require the integration of global and local redox proxies, and biotic records in the same stratigraphically well-constrained geological successions.During the early Cambrian, the Siberian Platform was a vast isolated, tropical continent almost entirely covered by an epicontinental sea (Fig. 1a)8,9. The platform supported a single metacommunity, i.e. a species pool with many local, interacting communities e.g.10, representing a third of total early Cambrian metazoan benthic diversity with widespread metazoan (archaeocyath sponge) reefs that formed bioherms (Fig. 1b)7,11. Dynamic and synchronous changes of body size in archaeocyath sponges, hyoliths, and helcionelloid molluscs through the early Cambrian on the Siberian Platform have been quantified, which coincide with elevated biodiversity and rates of origination: these have been proposed to follow OOEs12. Here we consider temporal changes in both the position of archaeocyath sponge reefs as a function of relative water depth, and in individual reef size (diameter), as well as the ecological complexity of the reef-building and dwelling communities by quantification of changing reef community membership of sessile archaeocyath sponge, coralomorph, and cribricyath species, on the Siberian Platform.Fig. 1: Palaeogeographic and stratigraphic position of the early Cambrian archaeocyath reefs of the Lena-Aldan area on the Siberian Platform.a Early Cambrian palaeofacies zonation map of the Siberian Platform. b Cross section to show relative positions of sampled transects along the Lena River11,40,66,67,68. c Lithostratigraphy, biostratigraphy, carbon isotope (δ13C)29,31,32 and carbonate-associated sulfate sulfur isotope (δ34SCAS)7 data for sections from the middle Lena River (Isit’, Zhurinsky Mys, Achchagy-Kyyry-Taas, and Achchagy-Tuoydakh). S.E.—Sinsk Event; Tolb.—Tolba Formation; ATD., BOT., N.-D., TOM.—Atdabanian, Botoman, Nemakit-Daldynian, and Tommotian local stages, respectively.Full size imageTo quantify ecological complexity, we used metacommunity analyses, which compare the structure between communities in terms of taxa (generally species) compositions spatially and temporally10 (see Methods). The ‘Elements of Metacommunity Structure’ framework used here is a hierarchical analysis that identifies properties in site-by-species presence/absence matrices that are related to the underlying processes, such as species interactions, dispersal, and environmental filtering that shape species distributions10. Application to various marine and terrestrial palaeocommunities has demonstrated the robustness of these methods to fossil data and sample size variations13,14. There are fourteen different types of metacommunity structure which are determined by the calculation of three metacommunity metrics: Coherence, Turnover, and Boundary Clumping, which reveal different controlling processes of underlying metacommunity structure10,15,16,17,18.The most ecologically complex metacommunities are classified as Clementsian, and have positive coherence, turnover and boundary clumping16. Clementsian metacommunities contain groups of taxa with similar range boundaries that respond to the environment synchronously as taxa have physiological or evolutionary trade-offs within the communities associated with environmental thresholds19. By contrast, when taxa respond individualistically to the underlying environment, without accounting for other taxa within the community, the structure is Gleasonian, and is defined by positive coherence and turnover but no significant boundary clumping16. When coherence is positive, but turnover is not significantly different from random, then the resultant metacommunity structures are known as quasi-structures (e.g. quasi-Clementsian), which reflect weaker underlying structuring processes.We determined the metacommunity structure for archaeocyath sponge species on the Siberian Platform throughout their early Cambrian record using an entire previously published data set11 then on a sub-set of metacommunities which had a sufficient number of reef sites to be suitable for analyses, i.e. with a sufficient number of sites to be statistically significant. Further, to investigate the effects of water depth on metacommunity structure, we used Spearman rank correlations to test whether the metacommunity ranking (as determined by reciprocal averaging, a type of correspondence analysis which ordinates the sites based on their species composition17), is significantly correlated to water depth. Finally, to quantify how pairwise associations between taxa change between the three temporally different metacommunities, we determined which pairwise taxa co-occurrences are significantly non-random using a combinatorics approach, and whether any non-random co-occurrences are positive or negative20.Species richness estimates are highly sensitive to differences in sampling. When comparing species richness of assemblages from several time intervals, it is advisable to standardise sampling across those assemblages to ensure that changes in species richness are not attributable to sampling differences. One approach is to subsample each time interval down to a standardised number of individuals (size-based rarefaction), but this approach can underestimate changes in richness because it tends to sample low-richness assemblages more completely than high-richness ones21. Coverage-based rarefaction, where each sample is down-sampled to a standardised level of taxonomic completeness, avoids this potential issue. The coverage of a sample is the proportion of species in the assemblage which are represented in that sample, and it can be estimated by subtracting the proportion of singletons in a sample from 1 (e.g.22; see also21 for details). We used the estimateD function from R package iNEXT23 to produce coverage-standardised species richness estimates with 95% confidence intervals, by repeatedly down-sampling the sampled assemblage from each time interval to match the coverage of the lowest-coverage interval. We did this by setting datatype = “abundance”, base = “coverage” and leaving all other arguments as default.In sum, we test the biotic response to OOEs by compiling metrics of archaeocyath reef size, location, and metacommunity complexity, integrated with existing data on archaeocyath individual size, species richness and origination and extinction rates12 and high-resolution geochemistry4,7 recalculated to the same stratigraphic scale, on the Siberian Platform over 11 Myr through Cambrian stages 2–3 (mid-Tommotian to early Botoman on the Siberian stratigraphic scale; 525–514 Ma). These results are used to quantify the community-wide response of metazoans to extrinsic redox cycles, and hence gain insight into the evolutionary processes involved.Geological setting and evolution of redoxDuring the early Cambrian shallow marine carbonates associated with evaporites and siliciclastics dominated the inner Siberian Platform, passing to shallow marginal carbonates of transitional facies known as the transitional zone (or the Anabar-Sinsk), thence to deep ramp and slope settings that accumulated organic-rich limestone and shale (Fig. 1a)24,25,26. Archaeocyathan reefs or bioherms were almost entirely restricted to the transitional facies. Such reefs appeared and proliferated during Cambrian stages 2 and 3 (Tommotian, Atdabanian and earliest Botoman), disappeared at the beginning of Stage 4 (middle Botoman) and re-appeared briefly at the end of this stage (Toyonian).We integrate palaeontological (archaeocyath species number and individual size), palaeoecological (reef size and palaeodepth location) and chemostratigraphic information (carbon isotope cycles 5p, 6p, and II–VII) for sections of the Aldan, Selinde and Lena rivers with sub-metre-scale lithostratigraphic subdivisions27,28,29,30,31,32,33 (Figs. 1c, 2a–c, 3a). This results in negligible uncertainty associated with sample heights, which are fixed relative to a consistent datum within each section.Fig. 2: Lithostratigraphy, biostratigraphy and carbon isotope (δ13C) data for sections of the Aldan and Selinde rivers bearing the earlierst archaeocyath reef communities of the Siberian Platform.a Dvortsy27,28,30 b Ulakhan-Sulugur33,34, and c Selinde69,70.Full size imageFig. 3: Summary of geochemical and biotic changes through the early Cambrian, Siberian Platform, and uranium isotope data representing a global record.a International and Siberian timescale, within age model C of 57. ND—Nemakit-Daldynian regional stage; U’-Y—Ust’-Yudoma Formation. b Summary of carbon and sulphur isotopes (from the Lena River, Siberia7). c Uranium isotopes from Siberia (grey; Sukharikha and Bol’shaya Kuonamka rivers), South China (blue), and Morocco (orange) (all data points are larger than 2SE)4. d Archaeocyath sponge species diversity and maximum diameter12. Plotted richness values are the species richness estimator21 with accompanying 95% confidence interval, calculated using the estimated function from R package iNEXT62. e Rates of archaeocyath sponge species origination and extinction12. f Reef location as a function of relative water depth (Supplementary Table 1). FWWB—Fair weather wave base. SWB—Storm weather wave base. g Reef/bioherm diameter, coloured by relative water depth (see column f, and Supplementary Table 2). h Number of reef community types (Supplementary Table 3). i Archaeocyath reef ecosystem complexity, with percentage of species co-occurrence as changing proportions of total non-random and positive and negative. G = Gleasonian, QG = Quasi-Gleasonian, C = Clementsian.Full size imageThroughout Cambrian stages 2 and 3, high-amplitude positive δ13C carbon isotope excursions show a strong positive covariation with the sulphur isotope composition of carbonate-associated sulphate (δ34SCAS) in sections from the Lena River (Fig. 3b)7. The rising limbs of these excursions are interpreted as intervals of progressive burial of reductants under anoxic bottom water conditions, and a progressive increase in atmospheric oxygen7. Coincident δ13C and δ34SCAS peaks (numbered II–VII) correspond with a pulse of atmospheric oxygen into the shallow marine environment (creating an OOE), followed by a corresponding decrease in reductant burial under more widespread marine oxia (falling limbs of δ13C and δ34SCAS), and leading to gradual de-oxygenation over Myr7. In addition, phosphorous retention might have occurred under oxic shallow marine conditions, acting to reduce primary productivity and further oxygenate the shallow marine environment in the short-term ( More

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Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USARobert C. Reiner Jr., Catherine A. Welgan, Christopher E. Troeger, Mathew M. Baumann, Aniruddha Deshpande, Brigette F. Blacker, Molly K. Miller-Petrie, Lucas Earl, Daniel C. Casey, Aubrey J. Cook, Farah Daoud, Nicole Davis Weaver, Samath Dhamminda Dharmaratne, Laura Dwyer-Lindgren, Valery L. Feigin, Joseph Jon Frostad, Kimberly B. Johnson, Alice Lazzar-Atwood, Kate E. LeGrand, Stephen S. Lim, Paulina A. Lindstedt, Laurie B. Marczak, Benjamin K. Mayala, Ali H. Mokdad, Jonathan F. Mosser, Chrisopher J. L. Murray, QuynhAnh P. Nguyen, David M. Pigott, Puja C. Rao, David L. Smith, Emma Elizabeth Spurlock & Simon I. HayDepartment of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, USARobert C. Reiner Jr., Samath Dhamminda Dharmaratne, Laura Dwyer-Lindgren, Stephen S. Lim, Ali H. Mokdad, Chrisopher J. L. Murray, David M. Pigott, Benn Sartorius, David L. Smith & Simon I. HayMalaria Atlas Project, University of Oxford, Oxford, UKDaniel J. Weiss & Susan Fred RumishaImperial College London, London, UKSamir BhattDepartment of Laboratory Medicine, Karolinska University Hospital, Huddinge, SwedenHassan AbolhassaniResearch Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, IranHassan Abolhassani & Nima RezaeiDepartment of Public Health, Debre Berhan University, Debre Berhan, EthiopiaAkine Eshete AbosetugnDepartment of Clinical Sciences, University of Sharjah, Sharjah, United Arab EmiratesEman Abu-GharbiehPopulation Health Sciences, King’s College London, London, EnglandVictor AdekanmbiCentre of Excellence for Epidemiological Modelling and Analysis, Stellenbosch University, Stellenbosch, South AfricaOlatunji O. AdetokunbohDepartment of Global Health, Stellenbosch University, Cape Town, South AfricaOlatunji O. AdetokunbohDepartment of Epidemiology and Biostatistics, Qom University of Medical Sciences, Qom, IranMohammad AghaaliFaculty of Medicine and Public Health, Jenderal Soedirman University, Purwokerto, IndonesiaBudi AjiMayo Evidence-based Practice Center, Mayo Clinic Foundation for Medical Education and Research, Rochester, MN, USAFares AlahdabJohn T. Milliken Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, USAZiyad Al-AlyClinical Epidemiology Center, Department of Veterans Affairs, St Louis, MO, USAZiyad Al-AlyInstitute of Health Research, University of Health and Allied Sciences, Ho, GhanaRobert Kaba AlhassanDepartment of Information Systems, College of Economics and Political Science, Sultan Qaboos University, Muscat, OmanSaqib AliInfectious and Tropical Disease Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, IranHesam AlizadeDepartment of Health Policy and Management, Kuwait University, Safat, KuwaitSyed Mohamed AljunidInternational Centre for Casemix and Clinical Coding, National University of Malaysia, Bandar Tun Razak, MalaysiaSyed Mohamed AljunidDepartment of Epidemiology, Arak University of Medical Sciences, Arak, IranAmir Almasi-Hashiani, Rahmatollah Moradzadeh & Maryam ZamanianMedical Research Center, Jazan University, Jazan, Saudi ArabiaHesham M. Al-MekhlafiDepartment of Parasitology, Sana’a University, Sana’a, YemenHesham M. Al-MekhlafiPediatric Intensive Care Unit, King Saud University, Riyadh, Saudi ArabiaKhalid A. Altirkawi & Mohamad-Hani TemsahResearch Group in Health Economics, University of Cartagena, Cartagena, ColombiaNelson Alvis-GuzmanResearch Group in Hospital Management and Health Policies, ALZAK Foundation, Cartagena, ColombiaNelson Alvis-GuzmanSchool of Medicine, University of Adelaide, Adelaide, SA, AustraliaAzmeraw T. AmareCollege of Medicine and Health Science, Bahir Dar University, Bahir Dar, EthiopiaAzmeraw T. AmareHealth Services Management Department, Arak University of Medical Sciences, Arak, IranSaeed AminiMaternal and Child Wellbeing, African Population and Health Research Center, Nairobi, KenyaDickson A. AmugsiPharmacy Department, Carol Davila University of Medicine and Pharmacy, Bucharest, RomaniaRobert AncuceanuCardiology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, RomaniaCatalina Liliana AndreiResearch Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, IranFereshteh AnsariRazi Vaccine and Serum Research Institute, Agricultural Research, Education, and Extension Organization (AREEO), Tehran, IranFereshteh AnsariDepartment of Parasitology, Mazandaran University of Medical Sciences, Sari, IranDavood AnvariDepartment of Parasitology, Iranshahr University of Medical Sciences, Iranshahr, IranDavood AnvariDepartment of Sociology and Social Work, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaSeth Christopher Yaw AppiahCenter for International Health, Ludwig Maximilians University, Munich, GermanySeth Christopher Yaw AppiahHealth Management and Economics Research Center, Iran University of Medical Sciences, Tehran, IranJalal Arabloo & Ahmad GhashghaeeDepartment of Public Health, Birmingham City University, Birmingham, UKOlatunde AremuFaculty of Nursing, Philadelphia University, Amman, JordanMaha Moh’d Wahbi AtoutSchool of Business, University of Leicester, Leicester, UKMarcel AusloosDepartment of Statistics and Econometrics, Bucharest University of Economic Studies, Bucharest, RomaniaMarcel Ausloos, Claudiu Herteliu & Adrian PanaGastro-enterology Department, University of Liège, Liège, BelgiumFloriane AusloosDepartment of Health Policy Planning and Management, University of Health and Allied Sciences, Ho, GhanaMartin Amogre AyanoreDepartment of Nursing, Debre Berhan University, Debre Berhan, EthiopiaYared Asmare AynalemDepartment of Reproductive Health, University of Gondar, Gondar, EthiopiaZelalem Nigussie AzenePublic Health Risk Sciences Division, Public Health Agency of Canada, Toronto, ON, CanadaAlaa BadawiDepartment of Nutritional Sciences, University of Toronto, Toronto, ON, CanadaAlaa BadawiUnit of Biochemistry, Sultan Zainal Abidin University (Universiti Sultan Zainal Abidin), Kuala Terengganu, MalaysiaAtif Amin BaigDepartment of Hypertension, Medical University of Lodz, Lodz, PolandMaciej BanachPolish Mothers’ Memorial Hospital Research Institute, Lodz, PolandMaciej BanachDepartment of Community Medicine, Gandhi Medical College Bhopal, Bhopal, IndiaNeeraj BediJazan University, Jazan, Saudi ArabiaNeeraj BediDepartment of Social and Clinical Pharmacy, Charles University, Hradec Kralova, Czech RepublicAkshaya Srikanth BhagavathulaInstitute of Public Health, United Arab Emirates University, Al Ain, United Arab EmiratesAkshaya Srikanth BhagavathulaSchool of Public Health, University of Adelaide, Adelaide, SA, AustraliaDinesh BhandariPublic Health Research Laboratory, Tribhuvan University, Kathmandu, NepalDinesh BhandariDepartment of Anatomy, Government Medical College Pali, Pali, IndiaNikha BhardwajDepartment of Community Medicine and Family Medicine, All India Institute of Medical Sciences, Jodhpur, IndiaPankaj BhardwajSchool of Public Health, All India Institute of Medical Sciences, Jodhpur, IndiaPankaj BhardwajDepartment of Statistical and Computational Genomics, National Institute of Biomedical Genomics, Kalyani, IndiaKrittika BhattacharyyaDepartment of Statistics, University of Calcutta, Kolkata, IndiaKrittika BhattacharyyaCentre for Global Child Health, University of Toronto, Toronto, ON, CanadaZulfiqar A. BhuttaCentre of Excellence in Women & Child Health, Aga Khan University, Karachi, PakistanZulfiqar A. BhuttaSocial Determinants of Health Research Center, Babol University of Medical Sciences, Babol, IranAli BijaniPlanning, Monitoring and Evaluation Directorate, Amhara Public Health Institute, Bahir Dar, EthiopiaTesega Tesega Mengistu BirhanuNutrition Department, St. Paul’s Hospital Millennium Medical College, Addis Ababa, EthiopiaZebenay Workneh BitewSt. Paul’s Hospital Millennium Medical College, Addis Ababa, EthiopiaZebenay Workneh BitewDepartment of Internal Medicine, Manipal Academy of Higher Education, Mangalore, IndiaArchith BoloorDepartment of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UKOliver J. BradySchool of Public Health and Health Systems, University of Waterloo, Waterloo, ON, CanadaZahid A. ButtAl Shifa School of Public Health, Al Shifa Trust Eye Hospital, Rawalpindi, PakistanZahid A. ButtCentre for Population Health Sciences, Nanyang Technological University, Singapore, SingaporeJosip CarDepartment of Primary Care and Public Health, Imperial College London, London, UKJosip Car & Salman RawafResearch Unit on Applied Molecular Biosciences (UCIBIO), University of Porto, Porto, PortugalFelix CarvalhoDepartment of Medicine, University of Toronto, Toronto, ON, CanadaVijay Kumar ChattuGlobal Institute of Public Health (GIPH), Thiruvananthapuram, IndiaVijay Kumar ChattuMaternal and Child Health Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, BangladeshMohiuddin Ahsanul Kabir ChowdhuryDepartment of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USAMohiuddin Ahsanul Kabir ChowdhuryFaculty of Biology, Hanoi National University of Education, Hanoi, VietnamDinh-Toi ChuLaboratory of Malaria Immunology and Vaccinology, National Institutes of Health, Bethesda, MD, USACamila H. CoelhoClinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, University of Milan, Milan, ItalyGiovanni DamianiDepartment of Dermatology, Case Western Reserve University, Cleveland, OH, USAGiovanni DamianiDepartment of Public Health, Ambo University, Ambo, EthiopiaJiregna Darega GelaDepartment of Pediatrics, Tanta University, Tanta, EgyptAmira Hamed DarwishToxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, IranAhmad DaryaniDivision of Women and Child Health, Aga Khan University, Karachi, PakistanJai K. DasWellcome Trust Brighton and Sussex Centre for Global Health Research, Brighton and Sussex Medical School, Brighton, UKKebede DeribeSchool of Public Health, Addis Ababa University, Addis Ababa, EthiopiaKebede DeribeSchool of Nursing and Midwifery, Haramaya University, Harar, EthiopiaAssefa DesalewDepartment of Community Medicine, University of Peradeniya, Peradeniya, Sri LankaSamath Dhamminda DharmaratneDepartment of Epidemiology and Biostatistics, Shahroud University of Medical Sciences, Shahroud, IranMostafa DianatinasabDepartment of Epidemiology, Shiraz University of Medical Sciences, Shiraz, IranMostafa DianatinasabCenter of Complexity Sciences, National Autonomous University of Mexico, Mexico City, MexicoDaniel DiazFaculty of Veterinary Medicine and Zootechnics, Autonomous University of Sinaloa, Culiacán Rosales, MexicoDaniel DiazDevelopment of Research and Technology Center, Ministry of Health and Medical Education, Tehran, IranShirin DjalaliniaDepartment of Medical Laboratory Sciences, Iran University of Medical Sciences, Tehran, IranFariba DorostkarInstitute of Microbiology and Immunology, University of Belgrade, Belgrade, SerbiaEleonora DubljaninSchool of Public Health, Hawassa University, Hawassa, EthiopiaBereket DukoSchool of Public Health, Curtin University, Perth, WA, AustraliaBereket Duko & Ted R. MillerCentre Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW, AustraliaAndem EffiongReference Laboratory of Egyptian Universities Hospitals, Ministry of Higher Education and Research, Cairo, EgyptMaysaa El Sayed ZakiPediatric Dentistry and Dental Public Health Department, Alexandria University, Alexandria, EgyptMaha El TantawiDepartment of Microbiology and Immunology, Suez Canal University, Ismailia, EgyptShymaa EnanyResearch Center for Environmental Determinants of Health, Kermanshah University of Medical Sciences, Kermanshah, IranNazir Fattahi & Masoud MoradiNational Institute for Stroke and Applied Neurosciences, Auckland University of Technology, Auckland, New ZealandValery L. FeiginResearch Center of Neurology, Moscow, RussiaValery L. FeiginAssociated Laboratory for Green Chemistry (LAQV), University of Porto, Porto, PortugalEduarda FernandesResearch Center on Public Health, University of Milan Bicocca, Monza, ItalyPietro FerraraInstitute of Gerontological Health Services and Nursing Research, Ravensburg-Weingarten University of Applied Sciences, Weingarten, GermanyFlorian FischerInstitute of Gerontology, National Academy of Medical Sciences of Ukraine, Kyiv, UkraineNataliya A. FoigtDepartment of Child Dental Health, Obafemi Awolowo University, Ile-Ife, NigeriaMorenike Oluwatoyin FolayanDepartment of Medical Parasitology, Abadan Faculty of Medical Sciences, Abadan, IranMasoud ForoutanDepartment of Dermatology, Kobe University, Kobe, JapanTakeshi FukumotoDepartment of Community Medicine, Datta Meghe Institute of Medical Sciences, Wardha, IndiaAbhay Motiramji Gaidhane, Zahiruddin Quazi Syed & Deepak SaxenaDepartment of Pediatric Nursing, Aksum University, Aksum, EthiopiaHailemikael Gebrekidan G. K. GebrekrstosSchool of Pharmacy, Aksum University, Aksum, EthiopiaLeake GebremeskelDepartment of Pharmacy, Mekelle University, Mekelle, EthiopiaLeake GebremeskelDepartment of Reproductive Health, Mekelle University, Mekelle, EthiopiaAssefa Ayalew GebreslassieTelethon Kids Institute, Perth Children’s Hospital, Nedlands, WA, AustraliaPeter W. GethingCurtin University, Bentley, WA, AustraliaPeter W. GethingDepartment of Biostatistics, Mekelle University, Mekelle, EthiopiaKebede Embaye GezaeInfectious Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, IranKeyghobad GhadiriPediatric Department, Kermanshah University of Medical Sciences, Kermanshah, IranKeyghobad GhadiriStudent Research Committee, Iran University of Medical Sciences, Tehran, IranAhmad GhashghaeeHealth Systems and Policy Research, Indian Institute of Public Health Gandhinagar, Gandhinagar, IndiaMahaveer GolechhaDepartment of Family and Community Medicine, University Of Sulaimani, Sulaimani, IraqMohammed Ibrahim Mohialdeen GubariDepartment of Pediatrics and Child Health, Mekelle University, Mekelle, EthiopiaFikaden Berhe HadguSchool of Health and Environmental Studies, Hamdan Bin Mohammed Smart University, Dubai, United Arab EmiratesSamer HamidiDepartment of Public Health, Wachemo University, Hossana, EthiopiaDemelash Woldeyohannes HandisoDepartment of Public Health, Jigjiga University, Jijiga, EthiopiaAbdiwahab Hashi & Muktar Omer OmerCenter for International Health (CIH), University of Bergen, Bergen, NorwayShoaib HassanBergen Center for Ethics and Priority Setting (BCEPS), University of Bergen, Bergen, NorwayShoaib HassanInstitute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, PakistanKhezar HayatDepartment of Pharmacy Administration and Clinical Pharmacy, Xian Jiaotong University, Xian, ChinaKhezar HayatSchool of Business, London South Bank University, London, UKClaudiu HerteliuDepartment of Urban Planning and Design, University of Hong Kong, Hong Kong, ChinaHung Chak HoKasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, IndiaRamesh Holla & Priya RathiInstitute of Research and Development, Duy Tan University, Da Nang, VietnamMehdi Hosseinzadeh & Yasser VasseghianDepartment of Computer Science, University of Human Development, Sulaymaniyah, IraqMehdi HosseinzadehCollege of Science and Engineering, Hamad Bin Khalifa University, Doha, QatarMowafa HousehSchool of Pharmaceutical Sciences, University of Science Malaysia, Penang, MalaysiaRabia HussainDepartment of Occupational Safety and Health, China Medical University, Taichung, TaiwanBing-Fang HwangDepartment of Health Promotion and Education, University of Ibadan, Ibadan, NigeriaSegun Emmanuel IbitoyeDepartment of Community Medicine, University of Ibadan, Ibadan, NigeriaOlayinka Stephen IlesanmiDepartment of Community Medicine, University College Hospital, Ibadan, Ibadan, NigeriaOlayinka Stephen IlesanmiFaculty of Medicine, University of Belgrade, Belgrade, SerbiaIrena M. IlicDepartment of Epidemiology, University of Kragujevac, Kragujevac, SerbiaMilena D. IlicResearch Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IranSeyed Sina Naghibi IrvaniDepartment of Environmental Health Engineering, Guilan University of Medical Sciences, Rasht, IranJalil JaafariHealth Informatic Lab, Boston University, Boston, MA, USATahereh JavaheriDepartment of Community Medicine, Dr. Baba Saheb Ambedkar Medical College & Hospital, Delhi, IndiaRavi Prakash JhaDepartment of Community Medicine, Banaras Hindu University, Varanasi, IndiaRavi Prakash JhaDepartment of Ophthalmology, Heidelberg University, Heidelberg, GermanyJost B. JonasBeijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, ChinaJost B. JonasDepartment of Family Medicine and Public Health, University of Opole, Opole, PolandJacek Jerzy JozwiakMinimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, IranAli KabirInstitute for Prevention of Non-communicable Diseases, Qazvin University of Medical Sciences, Qazvin, IranRohollah KalhorHealth Services Management Department, Qazvin University of Medical Sciences, Qazvin, IranRohollah KalhorDepartment of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, Jodhpur, IndiaTanuj KanchanInstitute for Epidemiology and Social Medicine, University of Münster, Münster, GermanyAndré KarchInternational Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, NigeriaGbenga A. KayodeJulius Centre for Health Sciences and Primary Care, Utrecht University, Utrecht, NetherlandsGbenga A. KayodeOpen, Distance and eLearning Campus, University of Nairobi, Nairobi, KenyaPeter Njenga KeiyoroDepartment of Public Health, Jordan University of Science and Technology, Irbid, JordanYousef Saleh KhaderDepartment of Global Health, University of Washington, Seattle, WA, USAIbrahim A. Khalil & Sonali KochharDepartment of Population Science, Jatiya Kabi Kazi Nazrul Islam University, Mymensingh, BangladeshMd Nuruzzaman KhanEpidemiology Department, Jazan University, Jazan, Saudi ArabiaMaseer KhanDepartment of Medical Microbiology & Immunology, United Arab Emirates University, Al Ain, United Arab EmiratesGulfaraz KhanFaculty of Health and Wellbeing, Sheffield Hallam University, Sheffield, UKKhaled KhatabCollege of Arts and Sciences, Ohio University, Zanesville, OH, USAKhaled KhatabDepartment of Medical Parasitology, Cairo University, Cairo, EgyptMona M. KhaterGlobal Evidence Synthesis Initiative, Datta Meghe Institute of Medical Sciences, Wardha, IndiaMahalaqua Nazli KhatibDepartment of Public Health, Kermanshah University of Medical Sciences, Kermanshah, IranNeda KianipourSchool of Traditional Chinese Medicine, Xiamen University Malaysia, Sepang, MalaysiaYun Jin KimDepartment of Nutrition, Simmons University, Boston, MA, USARuth W. KimokotiDepartment of Nursing and Health Promotion, Oslo Metropolitan University, Oslo, NorwaySezer KisaSchool of Health Sciences, Kristiania University College, Oslo, NorwayAdnan KisaGlobal Community Health and Behavioral Sciences, Tulane University, New Orleans, LA, USAAdnan KisaDepartment of Pediatrics, University of British Columbia, Vancouver, BC, CanadaNiranjan KissoonGlobal Healthcare Consulting, New Delhi, IndiaSonali KochharDepartment of Environmental Health Engineering, Arak University of Medical Sciences, Arak, IranAli KoolivandSchool of Population and Public Health, University of British Columbia, Vancouver, BC, CanadaJacek A. KopecArthritis Research Canada, Richmond, BC, CanadaJacek A. KopecCIBERSAM, San Juan de Dios Sanitary Park, Sant Boi de Llobregat, SpainAi KoyanagiCatalan Institution for Research and Advanced Studies (ICREA), Barcelona, SpainAi KoyanagiDepartment of Anthropology, Panjab University, Chandigarh, IndiaKewal KrishanInternational Institute for Population Sciences, Mumbai, IndiaPushpendra KumarFaculty of Health and Life Sciences, Coventry University, Coventry, UKOm P. KurmiDepartment of Medicine, McMaster University, Hamilton, ON, CanadaOm P. KurmiImperial College Business School, Imperial College London, London, UKDian KusumaFaculty of Public Health, University of Indonesia, Depok, IndonesiaDian KusumaPublic Health Foundation of India, Gurugram, IndiaDharmesh Kumar LalDepartment of Community and Family Medicine, University of Baghdad, Baghdad, IraqFaris Hasan LamiUnit of Genetics and Public Health, Institute of Medical Sciences, Las Tablas, PanamaIván LandiresMinistry of Health, Herrera, PanamaIván LandiresMedical Director, HelpMeSee, New York, NY, USAVan Charles LansinghGeneral Director, Mexican Institute of Ophthalmology, Queretaro, MexicoVan Charles LansinghDepartment of Otorhinolaryngology, Father Muller Medical College, Mangalore, IndiaSavita LasradoDepartment of Clinical Sciences and Community Health, University of Milan, Milan, ItalyCarlo La VecchiaSchool of Nursing, Hong Kong Polytechnic University, Hong Kong, ChinaPaul H. LeeCentre for Tropical Medicine and Global Health, University of Oxford, Oxford, UKSonia LewyckaOxford University Clinical Research Unit, Wellcome Trust Asia Programme, Hanoi, VietnamSonia LewyckaDepartment of Sociology, Shenzhen University, Shenzhen, ChinaBingyu LiDepartment of Systems, Populations, and Leadership, University of Michigan, Ann Arbor, MI, USAXuefeng LiuDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UKJoshua LongbottomIndependent Consultant, Melbourne, VIC, AustraliaAlan D. LopezRadiology Department, Egypt Ministry of Health and Population, Mansoura, EgyptHassan Magdy Abd El RazekGrants, Innovation and Product Development Unit, South African Medical Research Council, Cape Town, South AfricaPhetole Walter MahashaEnvironmental Health, Tehran University of Medical Sciences, Tehran, IranAfshin MalekiEnvironmental Health Research Center, Kurdistan University of Medical Sciences, Sanandaj, IranAfshin Maleki & Shadieh MohammadiInstitute for Social Science Research, The University of Queensland, Indooroopilly, QLD, AustraliaAbdullah A. MamunDepartment of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, IranMohammad Ali MansourniaCampus Caucaia, Federal Institute of Education, Science and Technology of Ceará, Caucaia, BrazilFrancisco Rogerlândio Martins-MeloICF International, DHS Program, Rockville, MD, USABenjamin K. MayalaDepartment of Pharmacy, Wollo University, Dessie, EthiopiaBirhanu Geta MeharieDepartment of Medical Laboratory Sciences, Bahir Dar University, Bahir Dar, EthiopiaAddisu MelesePeru Country Office, United Nations Population Fund (UNFPA), Lima, PeruWalter MendozaForensic Medicine Division, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaRitesh G. MenezesDepartment of Reproductive Health and Population Studies, Bahir Dar University, Bahir Dar, EthiopiaEndalkachew Worku MengeshaCenter for Translation Research and Implementation Science, National Institutes of Health, Bethesda, MD, USAGeorge A. MensahDepartment of Medicine, University of Cape Town, Cape Town, South AfricaGeorge A. MensahBreast Surgery Unit, Helsinki University Hospital, Helsinki, FinlandTuomo J. MeretojaUniversity of Helsinki, Helsinki, FinlandTuomo J. MeretojaClinical Microbiology and Parasitology Unit, Dr. Zora Profozic Polyclinic, Zagreb, CroatiaTomislav MestrovicUniversity Centre Varazdin, University North, Varazdin, CroatiaTomislav MestrovicPacific Institute for Research & Evaluation, Calverton, MD, USATed R. MillerInternal Medicine Programme, Kyrgyz State Medical Academy, Bishkek, KyrgyzstanErkin M. MirrakhimovDepartment of Atherosclerosis and Coronary Heart Disease, National Center of Cardiology and Internal Disease, Bishkek, KyrgyzstanErkin M. MirrakhimovHeidelberg Institute of Global Health (HIGH), Heidelberg University, Heidelberg, GermanyBabak Moazen & Shafiu MohammedInstitute of Addiction Research (ISFF), Frankfurt University of Applied Sciences, Frankfurt, GermanyBabak MoazenDepartment of Biostatistics, Hamadan University of Medical Sciences, Hamadan, IranNaser Mohammad Gholi MezerjiResearch Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj City, IranShadieh MohammadiHealth Systems and Policy Research Unit, Ahmadu Bello University, Zaria, NigeriaShafiu MohammedComputer, Electrical, and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi ArabiaPaula MoragaClinical Research Development Center, Kermanshah University of Medical Sciences, Kermanshah, IranMehdi NaderiResearch and Analytics Department, Initiative for Financing Health and Human Development, Chennai, IndiaAhamarshan Jayaraman NagarajanDepartment of Research and Analytics, Bioinsilico Technologies, Chennai, IndiaAhamarshan Jayaraman NagarajanDepartment of Pediatrics, Arak University of Medical Sciences, Arak, IranJavad NazariDisease Control and Environmental Health, Makerere University, Kampala, UgandaRawlance NdejjoDepartment of General Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, RomaniaIonut NegoiDepartment of General Surgery, Emergency Hospital of Bucharest, Bucharest, RomaniaIonut NegoiDepartment of Biological Sciences, University of Embu, Embu, KenyaJosephine W. NgunjiriInstitute for Global Health Innovations, Duy Tan University, Hanoi, VietnamHuong Lan Thi Nguyen & Hai Quang PhamSouth African Medical Research Council, Cape Town, South AfricaChukwudi A. Nnaji & Charles Shey WiysongeSchool of Public Health and Family Medicine, University of Cape Town, Cape Town, South AfricaChukwudi A. Nnaji & Charles Shey WiysongeCentre for Heart Rhythm Disorders, University of Adelaide, Adelaide, SA, AustraliaJean Jacques NoubiapUnit of Microbiology and Public Health, Institute of Medical Sciences, Las Tablas, PanamaVirginia Nuñez-SamudioDepartment of Public Health, Ministry of Health, Herrera, PanamaVirginia Nuñez-SamudioDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, CanadaAndrew T. OlagunjuDepartment of Psychiatry, University of Lagos, Lagos, NigeriaAndrew T. OlagunjuCentre for Healthy Start Initiative, Lagos, NigeriaJacob Olusegun Olusanya & Bolajoko Olubukunola OlusanyaDepartment of Pharmacology and Therapeutics, University of Nigeria Nsukka, Enugu, NigeriaObinna E. OnwujekweLaboratory of Public Health Indicators Analysis and Health Digitalization, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaNikita Otstavnov & Stanislav S. OtstavnovDepartment of Project Management, National Research University Higher School of Economics, Moscow, RussiaStanislav S. OtstavnovDepartment of Medicine, University of Ibadan, Ibadan, NigeriaMayowa O. OwolabiDepartment of Medicine, University College Hospital, Ibadan, Ibadan, NigeriaMayowa O. OwolabiDepartment of Respiratory Medicine, Jagadguru Sri Shivarathreeswara Academy of Health Education and Research, Mysore, IndiaMahesh P ADepartment of Forensic Medicine, Manipal Academy of Higher Education, Mangalore, IndiaJagadish Rao PadubidriDepartment of Health Metrics, Center for Health Outcomes & Evaluation, Bucharest, RomaniaAdrian PanaSchool of Global Public Health, New York University, New York, NY, USAEmmanuel K. PeprahDepartment of Parasitology and Entomology, Tarbiat Modares University, Tehran, IranMajid PirestaniUniversity Medical Center Groningen, University of Groningen, Groningen, NetherlandsMaarten J. PostmaSchool of Economics and Business, University of Groningen, Groningen, NetherlandsMaarten J. PostmaDepartment of Pharmacology, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaFaheem Hyder PottooDepartment of Nutrition and Food Sciences, Maragheh University of Medical Sciences, Maragheh, IranHadi PourjafarDietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, IranHadi PourjafarThalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranFakher RahimMetabolomics and Genomics Research Center, Tehran University of Medical Sciences, Tehran, IranFakher RahimSina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, IranVafa Rahimi-MovagharDepartment of Community Medicine, Maharishi Markandeshwar Medical College & Hospital, Solan, IndiaMohammad Hifz Ur RahmanDepartment of Oral Pathology, Srinivas Institute of Dental Sciences, Mangalore, IndiaSowmya J. RaoAcademic Public Health England, Public Health England, London, UKSalman RawafWHO Collaborating Centre for Public Health Education and Training, Imperial College London, London, UKDavid Laith RawafUniversity College London Hospitals, London, UKDavid Laith RawafSchool of Health, Medical and Applied Sciences, CQ University, Sydney, NSW, AustraliaLal RawalDepartment of Computer Science, Boston University, Boston, MA, USAReza RawassizadehSchool of Public Health, Haramaya University, Harar, EthiopiaLemma Demissie RegassaSchool of Social Sciences and Psychology, Western Sydney University, Penrith, NSW, AustraliaAndre M. N. RenzahoTranslational Health Research Institute, Western Sydney University, Penrith, NSW, AustraliaAndre M. N. RenzahoNetwork of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, IranNima RezaeiPediatric Infectious Diseases Research Center, Mazandaran University of Medical Sciences, Sari, IranMohammad Sadegh RezaiEpidemiology Research Unit Institute of Public Health (EPIUnit-ISPUP), University of Porto, Porto, PortugalAna Isabel RibeiroDepartment of Surgery, University of Minnesota, Minneapolis, MN, USAJennifer RickardDepartment of Surgery, University Teaching Hospital of Kigali, Kigali, RwandaJennifer RickardFaculty of Medical Sciences, Research Department, National University of Caaguazu, Cnel. Oviedo, ParaguayCarlos Miguel Rios-GonzálezDepartment of Research and Publications, National Institute of Health, Asunción, ParaguayCarlos Miguel Rios-GonzálezDepartment of Health Statistics, National Institute for Medical Research, Dar es Salaam, TanzaniaSusan Fred RumishaDepartment of Epidemiology, Shahid Beheshti University of Medical Sciences, Tehran, IranSiamak SabourDepartment of Phytochemistry, Soran University, Soran, IraqS. Mohammad SajadiDepartment of Nutrition, Cihan University-Erbil, Kurdistan Region, IraqS. Mohammad SajadiCenter for Health Policy & Center for Primary Care and Outcomes Research, Stanford University, Stanford, CA, USAJoshua A. SalomonDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranHossein Samadi KafilDepartment of Entomology, Ain Shams University, Cairo, EgyptAbdallah M. SamyDepartment of Surgery, Marshall University, Huntington, WV, USAJuan SanabriaDepartment of Nutrition and Preventive Medicine, Case Western Reserve University, Cleveland, OH, USAJuan SanabriaFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UKBenn SartoriusDepartment of Epidemiology, Indian Institute of Public Health, Gandhinagar, IndiaDeepak SaxenaGlobal Programs, Medical Teams International, Seattle, WA, USALauren E. SchaefferDepartment of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA, USALauren E. SchaefferEmergency Department, Manian Medical Centre, Erode, IndiaSubramanian SenthilkumaranCenter for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Shenzhen, ChinaFeng ShaPublic Health Division, An-Najah National University, Nablus, PalestineAmira A. ShaheenIndependent Consultant, Karachi, PakistanMasood Ali ShaikhUniversity School of Management and Entrepreneurship, Delhi Technological University, Delhi, IndiaRajesh SharmaCentre for Medical Informatics, University of Edinburgh, Edinburgh, UKAziz SheikhDivision of General Internal Medicine, Harvard University, Boston, MA, USAAziz SheikhInstitute for Population Health, King’s College London, London, UKKenji ShibuyaNational Institute of Infectious Diseases, Tokyo, JapanMika ShigematsuCollege of Medicine, Yonsei University, Seoul, South KoreaJae Il ShinDepartment of Law, Economics, Management and Quantitative Methods, University of Sannio, Benevento, ItalyBiagio SimonettiWSB University in Gdańsk, Gdansk, PolandBiagio SimonettiSchool of Medicine, University of Alabama at Birmingham, Birmingham, AL, USAJasvinder A. SinghMedicine Service, US Department of Veterans Affairs (VA), Birmingham, AL, USAJasvinder A. SinghNursing Care Research Center, Semnan University of Medical Sciences, Semnan, IranAmin SoheiliDepartment of Infectious Diseases, Kharkiv National Medical University, Kharkiv, UkraineAnton SokhanDivision of Community Medicine, International Medical University, Kuala Lumpur, MalaysiaChandrashekhar T. SreeramareddyDepartment of Community Medicine, Ahmadu Bello University, Zaria, NigeriaMu’awiyyah Babale SufiyanSchool of Medicine, University of California San Francisco, San Francisco, CA, USAScott J. SwartzJoint Medical Program, University of California Berkeley, Berkeley, CA, USAScott J. SwartzDepartment of Nursing, Aksum University, Aksum, EthiopiaDegena Bahrey TadesseDepartment of Midwifery, University of Gondar, Gondar, EthiopiaAnimut Tagele TamiruDepartment of Clinical Pharmacy, University of Gondar, Gondar, EthiopiaYonas Getaye TeferaDepartment of Epidemiology and Biostatistics, University of Gondar, Gondar, EthiopiaZemenu Tadesse TessemaK.A. Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Moscow, RussiaMariya Vladimirovna TitovaLaboratory of Public Health Indicators Analysis and Health Digitalization, Moscow Institute of Physics and Technology, Moscow, RussiaMariya Vladimirovna TitovaDepartment of Health Economics, Hanoi Medical University, Hanoi, VietnamBach Xuan TranFaculty of Geo-Information Science and Earth Observation, University of Twente, Enschede, NetherlandsPhuong N. TruongKasturba Medical College, Manipal Academy of Higher Education, Mangalore, IndiaBhaskaran UnnikrishnanAmity Institute of Biotechnology, Amity University Rajasthan, Jaipur, IndiaEra UpadhyayUKK Institute, Tampere, FinlandTommi Juhani VasankariDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyFrancesco S. ViolanteOccupational Health Unit, Sant’Orsola Malpighi Hospital, Bologna, ItalyFrancesco S. ViolanteCenter of Excellence in Behavioral Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, VietnamGiang Thu VuFoundation University Medical College, Foundation University Islamabad, Islamabad, PakistanYasir WaheedCultures, Societies and Global Studies, & Integrated Initiative for Global Health, Northeastern University, Boston, MA, USARichard G. WamaiSchool of Public Health, University of Nairobi, Nairobi, KenyaRichard G. WamaiDepartment of Human Nutrition and Food Sciences, Debre Markos University, Debre Markos, EthiopiaEmebet Gashaw WassieDepartment of Midwifery, Adigrat University, Adigrat, EthiopiaFissaha Tekulu WelayDepartment of Community Medicine, Rajarata University of Sri Lanka, Anuradhapura, Sri LankaNuwan Darshana WickramasingheDepartment of Epidemiology, Johns Hopkins University, Baltimore, MD, USAKirsten E. WiensDepartment of Neurology, University of Melbourne, Melbourne, VIC, AustraliaTissa WijeratneDepartment of Medicine, University of Rajarata, Saliyapura Anuradhapuraya, Sri LankaTissa WijeratneDepartment of Public Health, Samara University, Samara, EthiopiaTemesgen Gebeyehu WondmenehDepartment of Diabetes and Metabolic Diseases, University of Tokyo, Tokyo, JapanTomohide YamadaSchool of International Development and Global Studies, University of Ottawa, Ottawa, ON, CanadaSanni YayaThe George Institute for Global Health, University of Oxford, Oxford, UKSanni YayaDepartment of Nursing, Arba Minch University, Arba Minch, EthiopiaYordanos Gizachew YeshitilaCentre for Suicide Research and Prevention, University of Hong Kong, Hong Kong, ChinaPaul YipDepartment of Social Work and Social Administration, University of Hong Kong, Hong Kong, ChinaPaul YipDepartment of Neuropsychopharmacology, National Center of Neurology and Psychiatry, Kodaira, JapanNaohiro YonemotoDepartment of Public Health, Juntendo University, Tokyo, JapanNaohiro YonemotoDepartment of Epidemiology and Biostatistics, Wuhan University, Wuhan, ChinaChuanhua YuCancer Institute, Hacettepe University, Ankara, TurkeyDeniz YuceDepartment of Health Care Management and Economics, Urmia University of Medical Science, Urmia, IranHasan YusefzadehDepartment of Medicine, University Ferhat Abbas of Setif, Sétif, AlgeriaZoubida ZaidiSocial Development and Health Promotion Research Center, Kermanshah University of Medical Sciences, Kermanshah, IranAlireza ZangenehSchool of Medicine, Wuhan University, Wuhan, ChinaZhi-Jiang ZhangSchool of Public Health, Wuhan University of Science and Technology, Wuhan, ChinaYunquan ZhangHubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, ChinaYunquan ZhangDepartment of Health Education and Health Promotion, Kermanshah University of Medical Sciences, Kermanshah, IranArash ZiapourManaging the estimation or publication process. L.B.D. T.B.C. Writing the first draft of the manuscript. R.C.R.J. Primary responsibility for this manuscript focused on: applying analytical methods to produce estimates. L.B.D. T.B.C. Primary responsibility for this manuscript focused on: seeking, cataloguing, extracting, or cleaning data; production or coding of figures and tables. L.B.D. T.B.C. Providing data or critical feedback on data sources. L.B.D. T.B.C. and S.I.H. Development of methods or computational machinery. R.C.R.J. and L.B.D. T.B.C. Providing critical feedback on methods or results. L.B.D. T.B.C. and S.I.H. Drafting the manuscript or revising it critically for important intellectual content. R.C.R.J., L.B.D. T.B.C., and S.I.H. Management of the overall research enterprise (for example, through membership in the Scientific Council). L.B.D. T.B.C. and S.I.H. Consortia author contributions Managing the estimation or publication process. B.F.B., M.K.M.P. Writing the first draft of the manuscript. R.C.R.J. Primary responsibility for this manuscript focused on: applying analytical methods to produce estimates. C.A.W. Primary responsibility for this manuscript focused on: seeking, cataloguing, extracting, or cleaning data; production or coding of figures and tables. M.M.B. Providing data or critical feedback on data sources D.J.W., A.D., C.E.T., H.A., A.E.A., V.A., O.O.A., M.A., B.A., F.A., S.A., H.A., S.M.A., A.A.-H., N.A.-G., A.T.A., S.A., C.L.A., F.A., D.A., S.C.Y.A., J.A., O.A., M.A., F.A., Y.A.A., A.B., M.B., N.B., A.S.B., A.B., V.K.C., D.-T.C., G.D., J.D.G., A.D., S.D.D., M.D., A.E., M.El.S.Z., S.E., T.F., A.M.G., L.G., P.W.G., K.G., A.G., M.G., A.H., S.H., K.H., C.H., H.C.H., M.H., M.H., S.S.N.I., T.J., J.B.J., J.J.J., A.K., G.A.K., Y.S.K., I.A.K., M.N.K., M.K., K.K., M.N.K., Y.J.K., S.K., A.K., N.K., K.K., P.K., D.K., D.K.L., F.H.L., V.C.L., S.L., A.L.-A., K.E.L., S.S.L., P.A.L., X.L., H.M.A.E.R., M.A.M., B.K.M., W.M., R.G.M., E.M.M., B.M., N.M.G.M., S.M., S.M., A.H.M., M.M., A.J.N., J.N., I.N., J.W.N., Q.P.N., H.L.T.N., C.A.N., J.J.N., A.T.O., J.O.O., B.O.O., O.E.O., N.O., S.S.O., M.O.O., M.P.A., J.R.P., A.P., E.K.P., H.Q.P., M.P., M.J.P., H.P., Z.Q.S., F.R., V.R.-M., S.J.R., P.R., S.R., D.L.R., L.R., R.R., A.M.N.R., N.R., J.R., C.M.R.-G., S.S., S.M.S., A.M.S., B.S., D.S., A.A.S., M.A.S., J.I.S., J.A.S., A.S., E.S., C.T.S., S.J.S., D.B.T., A.T.T., B.X.T., P.N.T., B.U., E.U., T.J.V., Y.V., G.T.V., Y.W., R.G.W., T.W., C.S.W., T.G.W., S.Y., Y.G.Y., N.Y., C.Y., H.Y., Z.Z., A.Z., and S.I.H. Development of methods or computational machinery R.C.R.J., C.A.W., M.M.B., A.D., L.E., S.B., C.E.T., H.A., D.A., Y.A.A., A.S.B., D.C.C., V.K.C., F.D. A.D., M.D., M.E.S.Z., N.F., J.J.F., P.W.G., M.H., K.B.J., S.K., A., A.D.L., S.M., A.H.M., J.W.N., Q.P.N., S.F.R., A.M.S., E.E.S., S.J.S., E.U., Y.V., K.E.W., Y.G.Y., and N.Y. Providing critical feedback on methods or results C.A.W., A.D., C.E.T., H.A., A.E.A., E.A.-G., V.A., O.O.A., M.A., B.A., F.A., Z.A.-A., R.K.A., S.A., H.A., A.A.-H., H.M.A.M., K.A.A., N.A.-Gu., A.T.A., S.A., D.A.A., C.L.A., F.A., D.A., S.C.Y.A., J.A., O.A., M.M.W.A., M.A., F.A., Y.A.A., Z.N.A., A.B., M.B., A.S.B., D.B., N.B., P.B., K.B., O.J.B., Z.A.B., A.B., Z.W.B., A.B., Z.A.B., V.C., M.A.K.C., D.-T.C., C.H.C., G.D., J.D.G., A.H.D., A.D., J.K.D., K.D., A.D., S.D.D., M.D., D.D., S.D., F.D., B.D., L.D.-L., A.E., V.L.F., F.F., N.A.F., M.O.F., M.F., T.F., A.M.G., H.G.G.K.G., L.G., A.A.G., K.E.G., A.G., M.G., F.B.H., S.H., A.H., S.H., C.H., H.C.H., R.H., M.H., M.H., R.H., B.-F.H., S.E.I., O.S.I., I.M.I., M.D.I., S.S.N.I., T.J., R.P.J., J.B.J., J.J.J., A.K., R.K., T.K., A.K., G.A.K., P.N.K., Y.S.K., I.A.K., M.N.K., M.K., K.K., M.M.K., M.N.K., Y.J.K., R.W.K., S.K., A.K., N.K., S.K., A.K., J.A.K., A.K., K.K., P.K., O.P.K., D.K., D.K.L., S.L., K.E.L., S.L., B.L., X.L., A.D.L., H.M.A.E.R., P.W.M., A.A.M., M.A.M., L.B.M., F.R.M.-M., B.K.M., W.M., R.G.M., E.W.M., T.J.M., T.R.M., E.M.M., B.M., N.M.G.M., S.M., S.M., A.H.M., R.M., J.F.M., M.N., A.J.N., J.N., R.N., I.N., J.W.N., H.L.T.N., C.A.N., J.J.N., A.T.O., J.O.O., B.O.O., M.O.O., O.E.O., N.O., S.S.O., M.O.O., M.P.A., J.R.P., A.P., E.K.P., H.Q.P., M.J.P., F.H.P., H.P., Z.Q.S., F.R., V.R.-M., S.J.R., P.R., S.R., D.L.R., L.R., R.R., L.D.R., A.M.N.R., N.R., M.S.R., A.I.R., J.R., C.M.R.-G., S.S., S.M.S., J.A.S., H.S.K., A.M.S., J.S., B.S., D.S., L.E.S., S.S., F.S., A.A.S., M.A.S., A.S., K.S., M.S., J.I.S., B.S., J.A.S., D.L.S., A.S., E.E.S., C.T.S., M.B.S., D.B.T., A.T.T., Y.G.T., M.-H.T., Z.T.T., M.V.T., B.X.T., P.N.T., B.U., E.U., Y.V., F.S.V., G.T.V., Y.W., R.G.W., E.G.W., F.T.W., N.D.W., K.E.W., T.W., C.S.W., T.G.W., T.Y., S.Y., Y.G.Y., P.Y., N.Y., C.Y., D.Y., Z.Z., M.Z., Z.-J.Z., Y.Z., and S.I.H. Drafting the manuscript or revising it critically for important intellectual content R.C.R.J., C.A.W., M.K.M.-P., L.E., H.A., E.A.-G., V.A., O.O.A., M.A., B.A, F.A., R.K.A., H.A., A.A.-H., N.A.-G., A.T.A., S.A., D.A.A., R.A., C.L.A., J.A., O.A., M.M.W.A., M.A., F.A., M.A.A., Z.N.A., A.B., A.A.B., M.B., N.B. A.S.B., D.B., K.B., T.T.M.B., O.J.B., J.C., F.C., V.K.C., G.D., A.D., N.D.W., K.D., S.D.D., D.D., E.D., A.E., M.E.S.Z., M.E.T., S.E., V.L.F., E.F., P.F., F.F., N.A.F., M.O.F., M.F., T.F., A.M.G., L.G., A.G., M.I.M.G., D.W.H., A.H., S.H., C.H., H.C.H., R.H., M.H., S.E.I., O.S.I., I.M.I., M.D.I., S.S.N.I., J.J., R.P.J., J.B.J., J.J.J., A.K., A.K., G.A.K., M.N.K., M.K., G.K., K.K., M.M.K., M.N.K., A.K., N.K., A.K., A.K., K.K., P.K., O.P.K., D.K., I.L., S.L., C.L.V., P.H.L., K.E.L., J.L., A.D.L., H.M.A.E.R., P.W.M., A.M., A.A.M., M.A.M., L.B.M., F.R.M.-M., B.G.M., W.M., R.G.M., E.W.M., G.A.M., T.J.M., T.M., T.R.M., B.M., S.M., S.M., A.H.M., R.M., P.M., J.F.M., A.J.N., J.N., I.N., J.W.N., H.L.T.N., V.N.-S., A.T.O., J.O.O., B.O.O., M.O.O., O.E.O., N.O., S.S.O., M.O.O., M.P.A., J.R.P., A.P., H.Q.P., M.J.P., Z.Q.S., F.R., V.R.-M., M.H.U.R., S.J.R., S.R., D.L.R., L.R., N.R., A.I.R., J.R., C.M.R.-G., S.F.R., S.S., J.A.S., H.S.K., A.M.S., J.S., D.S., R.S., M.S., J.A.S., A.S., C.T.S., M.B.S., D.B.T., A.T.T., M.V.T., B.X.T., B.U., E.U., T.J.V., Y.V., F.S.V., G.T.V., R.G.W., N.D.W., K.E.W., T.W., .C.S.W., S.Y., Y.G.Y., Z.Z., M.Z., Z.-J.Z., and S.I.H. Management of the overall research enterprise (for example, through membership in the Scientific Council) B.F.B., A.J.C., P.W.G., J.A.K., A.H.M., C.J.L.M., P.C.R., J.A.S., B.S., and S.I.H. More

The categorisation system was developed through an iterative procedure including a careful evaluation at each stage. This was necessary because each of three rounds yielded substantial feedback from the expert taggers, identifying issues to be resolved and proposing improvements to the system. This process led to a much clearer understanding of the structure of sensitive data resources and a wider agreement on definitions to be applied in the tagging process. In addition, the allocation of exactly one tag per category improved during the development for many categories, indicating that the selection process was straightforward for most resources and categories. As a result, the categorisation system could be simplified and the structure improved, appropriately representing a trans-disciplinary effort. This may also be important from the user perspective. At the end of the day, the system should be so intuitive that the users searching for terms would have the same logic as the experts entered the tags.To be beneficial for the domain of LS, the categorisation system and the toolbox requires broad community approval38,39. In the project, we began the approval process with nominated experts from 6 LS RIs, embedded in a larger working group of the H2020-funded project EOSC-Life, covering 13 LS RIs. Though this can be seen as a useful starting point, the toolbox obviously needs community approval at a much larger scale. As the categorisation system is specifying a part of essential metadata for resources about sensitive data, it will be relevant to the FAIR Digital Objects (FDO) Forum for a « resources in the life sciences » FDO. The categorisation system can be used to derive FDO attributes and values for such FDOs. FDOs for the sensitive data itself, when levels of sensitivity and specific access protocols need to be specified is an interesting possible extension, and the categorisation system could support as a backbone information for access governance and technical choices. FDOs are to be “machine actionable”, so desirable mappings between different categorisation systems will be operationalisable. New European projects such as FAIRCORE4EOSC (https://faircore4eosc.eu/), FAIR-IMPACT (https://fair-impact.eu/) and other projects working on pragmatic semantic improvements for FAIR appliance will provide possibilities for registering metadata schemas and mappings that should reuse interdisciplinary approaches in the heterogeneous field of life sciences.The RDA has established and is maintaining a Metadata Standards Catalogue (MSC) (https://rdamsc.bath.ac.uk/mapping-index,5). An appropriate goal for the categorisation system would be to be included in this catalogue, after further refinement and alignment with other vocabularies addressing sensitive data in the life sciences. In any case, the work on the categorisation system can contribute to discussions on methodologies for aligning metadata schemas across scientific domains, while the categorisation system itself can be seen as an important contribution to the process of developing the most useful and appropriate cross-disciplinary terms and categories for describing sensitive data. We keep in mind that similar approaches have been applied via long and iterative processes in other scientific domains, such as understanding and predicting the evolution of climate (essential climate variables, https://public.wmo.int/en/programmes/global-climate-observing-system/essential-climate-variables) and essential biodiversity variables for mapping and monitoring species populations40. There are biases and gaps in the existing system that need to be tackled in the future. The initial content of the toolbox demonstrator, consisting of 110 resources related to sensitive data, has been primarily selected by four RIs with a focus on clinical and biomedical research (BBMRI, EATRIS, ECRIN, Euro-Bioimaging). Other areas and sensitive data types, such as environmental, classified, and proprietary data are under-represented, as are some disciplines, such as zoology, ecology, plant and mycological sciences, and microbiology. This indicates a need for a broader coverage of resources linked to sensitive data in the future work. Another question that needs to be investigated is how interoperable the categorisation system is with other domains outside the LS that systematically deal with sensitive data, for example, the Social Science and Humanities41). In addition, systematic data on the usability/user-friendliness of the toolbox from a broad sample of potential users from the life sciences are needed. Initial and informal evaluation of these aspects by the experts involved so far has been very positive but is clearly limited in scale and needs to be supplemented by more evidence.There are major challenges to the sharing of sensitive data, including interoperability, accessibility, and governance. The primary objective of the toolbox is to improve discoverability of resources and digital objects linked to the sharing and re-use of sensitive data (F in FAIR)4. The systematic application of a standardised typology for resources about sensitive data, as defined by the categorisation system, helps to better structure, and organise the issues and results in metadata enrichment (F4, R1.3 of the FAIR principles in Supplementary, Table S1). The toolbox alone will not be enough for the ‘I’ of the FAIR principles, but it may become a useful backbone for building more interoperable classification systems for sensitive data resources.It is perhaps more common to base findability on a tagging system using keywords (plus title text). That is, for example, how PubMed works—it does not categorise resources, it adds MESH terms to them (https://pubmed.ncbi.nlm.nih.gov/). Another option would have been to try to derive keywords from text or title. In our case, a categorisation system with pre-defined dimensions and pre-listed tags was preferred by the expert group. Keywords, in isolation, suffer from several disadvantages:

(a)

A range of equivalent terms may be used to mean the same thing – making searching for that concept difficult, requiring multiple ‘Or’ statements.

(b)

They may have multiple meanings (polysemy) especially if “drawn from”, or “applied to”, a wide range of scientific disciplines.

(c)

The different aspects of the resource covered by keywords, i.e., the types or dimensions of keyword applied, may be inconsistent and / or incomplete.

The categorisation system, on the other hand, guarantees that all 7 validated dimensions required are used in the tagging process and that the tags selected are standardised and defined. The toolbox categories also aid browsing of results by enabling sequential filtering using the categories and tags.In addition, there is a useful link between developing community approved categories for metadata, in this case for characterising resources dealing with sensitive data, and community understood (but implicit) ontologies used in the same area. Categories and ontologies can complement each other—without a common underlying ontology, metadata terms can be interpreted inconsistently, and without defining metadata categories, ontologies may remain implicit and inconsistent. We found, for example, that discussions on the best categorisation to use for scientific disciplines, or data types, exposed the implicit (and different) ontologies being used by different people and is based on the personal views of those in the group. Those would have been obviously rooted in and / or influenced by the language and working assumptions of their discipline(s), and their roles and experiences, (current and previous). That will be more and more the case with interdisciplinary research development and development in research careers. Developing categories in metadata can therefore play an important role in describing, understanding and, ultimately, harmonising the implicit ontologies scientists use in thinking about the area of sensitive data.In the development of the categorisation system, existing ontologies, classifications, and terminologies were taken into consideration (Table 2). However, many more have relationships to the categorisation system. An example is the Subject Resource Application Ontology (SRAO), an application ontology describing subject areas/academic disciplines used within FAIRsharing records by curators and the user community42. A first crosswalk has demonstrated considerable agreement between the toolbox category “research field” and subsections of SRAO42 and EDAM15. The toolbox has been registered as a resource (database) at FAIRsharing, a curated, informative, and educational resource on data and metadata standards, inter-related to databases and data policies (https://fairsharing.org/3577). It is planned to create a collection group of resources (standards, databases, policies) in FAIRsharing linked to the toolbox and the underlying categorisation system. This will also cover relationships to ontologies and classifications.There is a need to explore the applicability of the toolbox to specific domains. One example could be the European Joint Programme on Rare Diseases (EJP RD), where resources are made progressively FAIR at the record level to support innovative basic, translational and clinical research (https://www.ejprarediseases.org/coordinated-access-data-services/fairification-support/). The goal is to identify, refine and expose core standards for dataset interoperability, asset (data, sample, subject) discovery, and responsible data sharing, concentrating on data level rather than resource level information. Knowledge exchange between EJP RD and the toolbox could be of benefit in exploring the complementary of both approaches in adequately characterising resources linked to sensitive data and thus improving data discoverability.The first pilot study demonstrated major variation in tagging of resources if independent taggers are assessing the same resource (inter-observer variation). The example of BBMRI has shown that this variation can be considerably reduced if adequate training is performed; which in return is resource intense. Thus, to arrive at a valid and reliable tagging process, there is a necessity for adequate training and support to reduce inter-observer variation. Specific training sets and training programs as well as intercalibration tools need to be developed and implemented and approved by the community.Another option to be explored should be AI—or ML-algorithms to support automatic (or at least semi-automatic) tagging of resources. It is not easy to use AI/ML in this field due to the multilingualism and the misinterpretation of terms. Often there are different meanings between scientific disciplines and a common backbone for the application of AI/ML is difficult to achieve. It is necessary to come to a common understanding between people involved in the assessment of resources related to sensitive data in all life sciences. Nevertheless, the toolbox can become of major importance for research and application of AI/ML techniques in this field. It may serve as a resource for AI/ML to better find resources in the field by serving as a kind of gold standard to compare with. Another promising approach would be to consider a knowledge graph as an intelligent representation. For the categorisation system the approach could be used to interlink categories to a resource (e.g., “source related to sensitive data” has “geographical scope”) and to link individual tags between categories if possible (e.g., “clinical research data” result from “clinical research”). This would give a richer representation of the knowledge behind the categorisation system and the option to be integrated in existing approaches (e.g., OpenAIRE, https://www.openaire.eu/). Therefore, we will consider knowledge graphs as an intelligent knowledge representation of the categorisation system in the future.A major challenge will be the transition of the toolbox demonstrator to a mature toolbox and ultimately its maintenance, extension, and sustainability. Development of the toolbox demonstrator has been financed by EOSC-Life, but this project will end in 2023. Discussion on sustainability has been initiated with several life-science infrastructures (e.g., BBMRI, EATRIS, ECRIN and ELIXIR, another European Life-Science Infrastructure). Key aspects of sustainability that need to be considered are maintenance of the toolbox portal and tagging tool and of the toolbox content including expert time for tagging as well as human resources to maintain the system. Different approaches are under evaluation: an organization considering the resource core to its operations and taking full responsibility, or a joint ownership across multiple organisations (e.g., multiple RIs) or a community taking responsibility, either funded by future grants or through in-kind contributions from motivated research parties/individuals. Further costs to be covered will include system maintenance, input from a toolbox manager, tagging of resources by experts, as well as advertisement to the envisioned user groups, hardware costs and costs for debugging and major extension of functionality if needed. More

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