A prospective multicenter birth cohort study of iron adaptive homeostasis, growth and development in three Peruvian regions

Lead Research Organisation: Queen Mary University of London
Department Name: Blizard Institute of Cell and Molecular

Abstract

Peru is a South American country which in the last two decades has experienced a continuous economic growth and has improved its population wealth. However, in Peru still a large proportion of children are suffering from anaemia due to insufficient iron levels in their blood. That situation generates a great hazard to the future of Peruvian children and their adult health. The roots of this problem are likely to be complex because numerous ecological, biological, social and political factors explain in part the persistence of anaemia. The majority of the government interventions are currently focussed on treatment and not to prevention. However, treating this disease might have side effects, as too much iron, interacting with other nutritional or environmental factors, can also negatively affect growth and development.

In this project, we will study the complexity of environmental and nutritional factors that alter the mechanisms of iron balance in a group of Peruvian babies, from birth to their first year of life. Children and their mothers will be studied in 3 cities in Peru located on the coast, the Andes and the Amazon. Various measurements and samples of water, blood, faeces will be made; baby size measurement, interviews, nutritional observation and focus groups with participating mothers will be collected. Some health policies and strategies implemented in the past will also be evaluated.

Technical Summary

Background.
Despite economic growth and improvement of development indicators, Peru has a high prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA), for reasons that are unclear. A complexity of eco-bio-social-political factors underlies anaemia and it will be posing increased pressure on the most marginalised people, if not addressed adequately, from an integrative sustainable perspective. Most government interventions are aimed at treatment and not prevention.

Aim: To understand the complexity of environmental, social, and nutritional factors altering mechanisms of adaptive iron homeostasis in infants during the Anthropocene.

Methods: This is a multicentre prospective cohort study with an eco-bio-social-political approach in 3 cities of Peru located in the Coast, Andes and Amazon.

Study period: April 2019 to March 2022 (36 months) Study population: healthy newborns at > 34 weeks of gestation, born in 2020. Follow-up: Prenatal (mothers), then at birth and at months 4, 6, 8 and 12 (mother-infant pairs).
Exposure: nutritional or environmental factors that modify iron homeostasis. Outcomes: Primary Outcome: Iron Deficiency; Secondary outcomes: IDA, delay in infant growth.

Measurements: Ecological/Environmental: Water samples, GIS-mapping. Biological: Mother and infant: Blood, stool samples; anthropometric assessment according to standard procedures. Social: nutritional household survey; 24 hours of nutritional observation, in-depth interviews and focus groups with participating mothers. Political/Economic: Policy and capacity analysis, focus groups with stakeholders.

Official Development Assistance
This research will contribute to the social and economic development of Peru by addressing the complexity of factors determining iron deficiency anaemia in distinct parts of Peru.

Ethics
An Institutional Research Ethics Committee will review the study protocol at the Instituto Nacional de Salud del Niño (Peru) and at QMUL (London, UK).

Planned Impact

Peru is a country that is known for its biodiversity and cuisine but struggles with populations who do not have access to quality and varied nutrition or suffer from food insecurity. Four in every 10 children between 6- 36 months in Peru suffer from anaemia, with potentially detrimental effects on their development and future health.

This research is directly aimed at infants, the future of Peru: in particular, those infants whose mothers do not have access to quality food, sanitation and live in deteriorated ecosystems. To break the vicious cycle that has been embodied for so long by society and been described by Anibal Quijano as continued coloniality, this research will use a participatory approach to assess the complexity of factors that determine iron deficiency anaemia in Peru, in order to plan future interventions.

This research will use an integrative systemic approach. It is sustainable as it addresses the complexity of eco-bio-social-political factors by facilitating the process of collaboration. It directly involves all key stakeholders from the onset, starting with engaging community/ grassroots level actors and government stakeholders and integrating them into research design and policy development.
 
Description New research collaborator for physicochemical and microbiological analysis 
Organisation Center for Technological, Biomedical and Environmental Research
Country Peru 
Sector Academic/University 
PI Contribution The new collaboration with the Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales (CITBM), which is a Centre for Research Excellence at the University of San Marcos in Lima, will allow for support to strengthening and expanding existing expertise. We will be collaborating with two research groups within the CITBM, on physics and microbiological expertise. There will be a support to the new partner through research capacity building in the area of heavy metal analysis in blood samples and microbiological analysis of stool samples, the latter will be shipped to QMUL for genomic analysis.
Collaborator Contribution The ARPEC project will receive a technological contribution of CITBM for the physicochemical and microbiological study of environmental samples. CITBM will be leading on the analysis of these research results and we will work collaboratively on results publication. Furthermore, CITBM will secure part of the microbiological research carried out in faecal samples of the participants.
Impact This collaboration is currently starting, outputs are expected for late 2021/early 2022.
Start Year 2020
 
Description 1st Experts Meeting on Anaemia (Peru) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact On 07Feb2020 Dr Carlos Delgado and Dr Victor Sanchez, from the Peruvian partner Institution Instituto Nacional de Salud del Niño presented ARPEC Project during the 1st Expert Meeting on Anaemia "Grupo de Expertos - Anemia" at the National Centre of Strategic Planning - CEPLAN. This event was organized by the Ministry of Development and Social Inclusion of Peru, the Office of Government Compliance and Sector Innovation (OCG) of the Presidency of the Council of Ministers. The attendees were Peruvian Ministries representatives, policymakers, researchers, health practitioners and academics. The topics of the event were aimed to highlight the current landscape of anaemia research, indicators across Peru and innovations to diminish its prevalence and incidence rates. It is expected that the findings influence the government programs and the institution's next steps.
Year(s) Of Engagement Activity 2020
URL https://twitter.com/MidisPeru/status/1225851180515053574
 
Description Annual paediatric research event "LVII Reunião Anual da Sociedade Latino Americana de Investigação Pediátrica - SLAIP" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact On 12Nov2019 Dr. Carlos Delgado, from the Peruvian partner institution Instituto Nacional de Salud del Niño presented ARPEC project through a poster presentation at the LVII Reunião Anual da Sociedade Latino Americana de Investigação Pediátrica - SLAIP held at Universidade de São Paulo - FMRP-USP, Brazil.
Year(s) Of Engagement Activity 2019
URL http://rpp.fmrp.usp.br/slaip2019/index.php/fotos-da-slaip-2019
 
Description Bi-Annual ARPEC Project Team meetings - Study Launch events 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact 22-23Jun2019 - Study launch event at Pucallpa, Peru
Venue: Universidad Nacional Intercultural de la Amazonia (UNIA). Pucallpa, Peru.
Topics: Presentation of ARPEC study protocol, general scope and objectives. Study chronogram and collaborators.
Attendees: President of the Organising Committee of the UNIA, Representatives of local and regional authorities (Yarinacocha mayor, representative of the Peruvian Vice Ministry of Health - MINSA) representatives of the three Peruvian collaborating institutions, QMUL staff, public.

24-25Jun2019 - Study launch event at Ayacucho, Peru.
Venue: Universidad Nacional San Cristóbal de Huamanga (UNSCH) Ayacucho, Peru.
Topics: Presentation of ARPEC study protocol, general scope and objectives. Study chronogram and collaborators.
Attendees: President of the UNSCH, representatives of local authorities, representatives of the three Peruvian collaborating institutions and QMUL staff.

26Jun2019 - Study launch event at Lima, Peru.
Venue: Instituto Nacional de Salud del Niño (INSN) Lima, Peru.
Topics: Presentation of ARPEC study protocol, general scope and objectives. Study chronogram and collaborators.
Attendees: Director of the INSN, Ambassador of UK Embassy in Peru, Health practitioners, representatives of the three Peruvian collaborating institutions and QMUL staff.
Year(s) Of Engagement Activity 2019
URL https://www.qmul.ac.uk/media/news/2019/smd/new-study-aims-to-prevent-anaemia-in-peruvian-children.ht...
 
Description Bi-Annual ARPEC Project Team meetings - Study coordination and capacity building events 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact 1-2Nov2019 - Study coordination / Work meeting at Lima, Peru
Venue: Instituto Nacional de Salud del Niño (INSN) Lima, Peru.
Topics: Updates and challenges of the study implementation in Lima. Review and work on the study protocol amendment, manuals of procedures, and function manuals.
Attendees: Representatives of the three Peruvian collaborating institutions and QMUL staff.

4-5Nov2019 - Capacity Building workshops at Pucallpa, Peru
Venue: Nursing College of Pucallpa, Peru.
Topics: Presentation of ARPEC study protocol, general scope and objectives. Ethics on research (theory and practical cases) study chronogram and clinical assessments.
Attendees: health professionals (nurses, midwives) from 5 health centres of Pucallpa, representatives of the three Peruvian collaborating institutions and QMUL staff.

7-8Nov2019 - Capacity Building workshops at Ayacucho, Peru.
Venue: Nursing Faculty of Universidad Nacional San Cristóbal de Huamanga (UNSCH) Ayacucho, Peru.
Topics: Presentation of ARPEC study protocol, general scope and objectives. Ethics on research (theory and practical cases) study chronogram and clinical assessments.
Attendees: health professionals (nurses, midwives) from Ayacucho Hospital Nazarenas, representatives of the three Peruvian collaborating institutions and QMUL staff.
Year(s) Of Engagement Activity 2019
URL https://www.qmul.ac.uk/arpecproject/news-and-events/
 
Description Class presentation on "La Anemia y la Evidencia. Un caso emblemático de Presupuesto por Resultados" [Anemia and the Evidence. An emblematic case of Budgeting for outcomes] 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact On 27th of January. 2021 Dr. Doreen Montag guest-lectured the class entitled: "Anemia and the Evidence. An emblematic case of Budgeting for outcomes". This class was part of the Course of Public Management for Results in the Master of Management and Auditing of the Catholic University of Trujillo, Peru.
Year(s) Of Engagement Activity 2021
 
Description Institute of Population Health Sciences and Queen Mary Latin American Network Seminar "An eco-bio-socio-political approach to anaemia in Peru" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact On 11Dec2019 Dr Doreen Montag presented ARPEC Project at the Institute of Population Health Sciences (IPHS) Seminar at Queen Mary University of London. This Seminar was co-organized by IPHS with the QMUL Latin American Network (QMLAN) and was attended by staff and students of the postgraduate and undergraduate level of the university. The presentation highlighted the eco-bio-socio-political approach of the project across the three ecological Peruvian regions.
Year(s) Of Engagement Activity 2019
 
Description Meeting and Press interview of Doreen Montag (QMUL) with the Head of the Health Network of Huamanga, Ayacucho 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact On 14Aug2019, Dr Doreen Montag attended a meeting with the Head of the Health Network of Huamanga, Ayacucho, to discuss further collaboration related to the implementation of Project ARPEC in Ayacucho.
Year(s) Of Engagement Activity 2019
URL https://www.facebook.com/400178840735199/videos/2272837772933284/?t=2
 
Description Meeting and Press interview of Doreen Montag (QMUL) with the Regional Government of Ucayali, Peru 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact On 13Aug2019, Dr Doreen Montag attended a meeting with the Regional Governor of Ucayali, to discuss further collaboration related to the implementation of Project ARPEC in Pucallpa.
Attendees: Representatives of regional authorities of Ucayali, representatives of the Peruvian collaborating institution UNIA and Dr Doreen Montag.
Year(s) Of Engagement Activity 2019
URL https://www.facebook.com/watch/?v=518187832288799
 
Description Meeting and Press interview of Doreen Montag (QMUL) with the district Mayor of Yarinacocha 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact On 05Aug2019, Dr Doreen Montag attended a meeting with the local mayor of Yarinacocha, to discuss further collaboration related to the implementation of Project ARPEC in Pucallpa.
Attendees: Mayor of the Municipality of Yarinacocha, and other representatives of local authorities of the district of Yarinacocha, representatives of the Peruvian collaborating institution UNIA and Dr Doreen Montag
Year(s) Of Engagement Activity 2019
URL https://www.facebook.com/watch/?v=345010383041422
 
Description Open Lecture and Seminar "An eco-bio-socio-political approach to anaemia in Peru" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact On 23Nov2019 Dr Doreen Montag presented ARPEC Project at the Open Lecture and Seminar for the MSc Programme on "Public Health and Health Policy" and "Primary Health Care" at the School of Medicine of the Aristotle University of Thessaloniki, Greece. The event, attended by students of the university and general public, highlighted the bio, social, political and environmental approach of the project across the different ecological regions of Peru.
Year(s) Of Engagement Activity 2019
 
Description PRESENTACIÓN DEL TRABAJO EN PROGRESO DEL PROYECTO ARPEC "Cohorte piloto de nacimientos 2021 para el estudio multicéntrico prospectivo de la homeostasis adaptativa del hierro, el crecimiento y el desarrollo infantil en tres regiones peruanas". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact On March 15th, we presented our ARPEC work in progress at the the National University of San Cristobal de Huamanga, Ayacucho, Peru. Several participants and some with family members, local government , hospital collaborators, and academics participated. The photovoice results were presented and one participant explained some of the photos she took in Ayacucho to the audience.
Year(s) Of Engagement Activity 2023
 
Description PRESENTACIÓN DEL TRABAJO EN PROGRESO DEL PROYECTO ARPEC "Cohorte piloto de nacimientos 2021 para el estudio multicéntrico prospectivo de la homeostasis adaptativa del hierro, el crecimiento y el desarrollo infantil en tres regiones peruanas". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact On March 13th, we presented our ARPEC work in progress at the the National Institute of Child Health (INSN), Lima, Peru. Several participants, some with family members, policy makers- ministerial representatives, representative from our external advisory board, third sector organization presentation, hospital collaborators, and other inter institutional collaborators participated. The photovoice results were presented and one participant explained some of the photos she took in Lima to the audience.
Year(s) Of Engagement Activity 2023
 
Description PRESENTACIÓN DEL TRABAJO EN PROGRESO DEL PROYECTO ARPEC "Cohorte piloto de nacimientos 2021 para el estudio multicéntrico prospectivo de la homeostasis adaptativa del hierro, el crecimiento y el desarrollo infantil en tres regiones peruanas". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact We presented our ARPEC work in progress to participants, their families and policy makers at the National Intercultural University of the Amazon in Pucallpa, Peru, on March 10th. Due to heavy rain and flooding in the city that afternoon on 10th of March, 2023, the audience was very limited and only consisted of our research team, a few participants and their family members and one regional government representative. However, it was also the first time we presented preliminary results and advances among our research circle, which was very important. The photovoice results were presented and one participant explained some of the photos she took in Pucallpa to the audience.
Year(s) Of Engagement Activity 2023
 
Description Participation in a round table on "Women in Research" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact On 21Sept2020 Dr. Doreen Montag gave an overview of the challenges of science and the presence of women in research as a dynamic agent. The activity was aimed at researchers, decision-makers and representatives of the public sector, the academic sector and third sector organisations, linked to science, education, and technology. This event was organised and supported by the British Council and the Peruvian Research Body Concytec's Pro Women Committee.
Year(s) Of Engagement Activity 2020
URL https://portal.concytec.gob.pe/index.php/noticias/2347-comite-pro-mujer-participa-en-semana-nacional...
 
Description Peruvian National Research body - CONCYTEC mentoring webinar for young female researchers 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact On November 26th 2020, Dr Doreen Montag took part as a facilitator in the education course of "capacitated voluntary mentors" (Mentores Voluntarios Capacitados (MVC)), organised by the British Council in Peru together with CONCYTEC and the Comité ProMujer en CTI de CONCYTEC.
Year(s) Of Engagement Activity 2020
 
Description Presentations of COVIDA Project results (January 2021) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact On 21Jan2021 Dr. Carlos Delgado, Director of ARPEC circle in Peru presented the analysis and outcomes of COVIDA 2021, a monitoring study including more than 4,000 COVID-19 patients. The monitoring was done by a voluntary medical brigade from the TeleHealth Unit of Universidad Nacional Mayor de San Marcos - UNMSM.
The consensus highlighted the need to know and recognising the warning signs and the correct application of the tools to determine the health status of the patient under monitoring to identify the opportune moment in which they should be referred to a health centre. In addition, it was recommended that the disease should mostly be managed at the first level of care to avoid overwhelming the scarce intensive care services.
Year(s) Of Engagement Activity 2021
URL https://unmsm.online/telesalud/index.php/2021/01/21/unidad-de-telesalud-comparte-los-logros-obtenido...
 
Description Seminar "An eco-bio-socio-political approach to anaemia in Peru" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact On 13Feb2020 Dr Doreen Montag presented ARPEC Project in the Public collection events "Talks of Interest to Medical Sciences" and "School of Anthropology and Museum Ethnography Seminars Series" at Oxford University, School of Anthropology and Museum Ethnography. The talk, attended by students of the university and general public, highlighted the bio-eco-socio-political approach of the project across the different ecological regions of Peru.
Year(s) Of Engagement Activity 2020
 
Description Talk on MICROBIOTA, BIODIVERSIDAD, SALUD Y GASTRONOMÍA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Invited to give a talk on MICROBIOTA, BIODIVERSIDAD, SALUD Y GASTRONOMÍA for the event "El Sabor del Futuro" on June 16th 2021, organized by the Programa de Gastronomía PUCP (Pontificia Universidad Católica del Perú, asociación La Revolución and PUCA- Peruanos Unidos por la Cocina y la Alimentación, Lima Peru.
Year(s) Of Engagement Activity 2021
URL http://encuentro.pucp.edu.pe/sabordelfuturo/ponentes-eventos/?seccion=ponentes
 
Description Talk/Debate on the relationship between health professionals and patients 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact On December 15th 2020, Dr Doreen Montag has given a talk and participated in a roundtable on the relationship between health professionals and patients as opening event for the launch of the Master's programme in Health Communication at the Pontificia Universidad Catolica del Peru.
Year(s) Of Engagement Activity 2020
URL https://puntoedu.pucp.edu.pe/noticias/conoce-la-nueva-maestria-en-comunicacion-en-salud-de-la-escuel...
 
Description Taller "Desafíos y oportunidades que enfrentan los sistemas alimentarios: Enfoque ciudadano" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Workshop participation on "Desafíos y oportunidades que enfrentan los sistemas alimentarios: Enfoque ciudadano", as part of Diálogos Nacionales hacia la Cumbre Mundial de la ONU sobre los Sistemas Alimentarios. 1st of July 2021, Lima, Peru
Year(s) Of Engagement Activity 2021
 
Description Taller para Jóvenes - Cambio Climático y Biodiversidad en el Perú 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact Workshop for young people on - Cambio Climático y Biodiversidad en el Perú, part of the Colloquium on Ciencia y Sociedad "El Jardín Botánico Nacional del Perú", co-organized by CONCYTEC, British Council, la Universidad Científica del Sur, British Embassy in Peru, Profonanpe, la Asociación Pro Jardín Botánico Nacional, among others. 19-22.04.2021
Year(s) Of Engagement Activity 2021
URL https://www.britishcouncil.pe/events/cambio-climatico-biodiversidad
 
Description The Global Health Network Conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact It was an international conference for south-south relationship building, taking place in South Africa. It was therefore unique and not composed of the usual audience of engagement activities for our Peruvian team partners, who participated. Our team submitted a proposal for evaluation of its oral presentation, but it was selected only for publication in the abstract notebook. The traveling researchers attended lectures and interacted with other researchers.
Year(s) Of Engagement Activity 2022
URL https://uctcmc.eventsair.com/the-global-health-network-conference-2022/
 
Description What has anthropology got to do with a transdisciplinary research project on childhood anaemia and iron homeostasis in Peru? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact This was an invited talk as part of Queen Mary University of London global health week for medical students as part of their undergraduate medical training.
Year(s) Of Engagement Activity 2022
 
Description Working group for the National Clinical Guideline for prevention, diagnosis, treatment for iron deficiency anaemia for children, adolescents, pregnant and puerperal women 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact In December 2020 Dr. Carlos del Aguila and BSc. Victor Mamani, from ARPEC team of Instituto Nacional del Niño - INSN joint the national writing group to create the "National Clinical Guideline for prevention, diagnosis and treatment for iron deficiency anaemia in children, adolescents, pregnant and puerperal women". These Guidelines are expected to incorporate the latest available evidence for the groups affected by the highest prevalence rates of anaemia. The document that is currently being finalised will generate a considerable impact across clinical practitioners and public health professionals and the population groups targeted by it.
Year(s) Of Engagement Activity 2020
 
Description seminar presentation: COVID-19 within the Context of Planetary Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dr Doreen Montag gave a seminar on "COVID-19 within the Context of Planetary Health" for the academic community at Campus Fryslân, University of Groningen. The idea was to discuss planetary health through a COVID-19 lens, looking at biodiversity loss and environmental degradation and unsustainable development, which are directly linked as risk factors to anaemia. The presentation sparked interest
Year(s) Of Engagement Activity 2021