Operational gaps in the Global Polio Eradication Initiative implementation had been partly responsible for inadequate population immunity and the continued transmission of wild poliovirus in Nigeria before the African Region was declared polio-free in 2020. Missed opportunities to provide services in nomadic populations due to frequent mobility, lack of inclusion in microplans and the remoteness of their settlements were the major challenges. During May 2013 we conducted immunization outreach to nomadic and other underserved communities in Rabah LGA, Sokoto state, and Ardo Kola LGA, Taraba state, in Nigeria to identify and vaccinate children missed during supplemental immunization activities while identifying missed acute flaccid paralysis cases.An enumeration checklist and data collection instruments on Android cell phones were used to capture socio-demographic data and GPS coordinates on nomadic settlements, households, number of children aged <5 years, children previously missed for vaccination and their locations. Local guides led trained enumerators to underserved communities for the enumeration and vaccination. Data were analyzed using Microsoft Excel 2007.A total of 324 settlements were listed for the two states, and 111 (34.3%) of these were identified as missed when compared with micro-planning for the most recent SIA. In these settlements, 3,533 households and 9,385 children aged <5 years were listed. We administered oral poliovirus vaccine to all 1,946 missed children during the recent or any supplemental immunization activities. Of these, 527 (27.1%) had never been vaccinated. We found no missed acute flaccid paralysis cases.Nomadic populations continue to be underserved, especially for vaccination services. This results in pockets of populations with low herd immunity and increased risk for poliovirus transmission. Community leaders and nomadic settlements should be included in the micro-planning of all supplemental immunization activities to ensure all children receive vaccination services. The wild poliovirus (WPV) transmission remains endemic in two countries  -4. BeforThe movement of nomads and migrant populations has been identified as a reservoir for the sustained transmission of poliovirus -9. BecauGiven the high mobility of nomads, systematic surveillance data on the health status of these populations have been difficult to obtain. Most surveillance information is based on specific, often small-scale studies - each one providing information on a limited portion of the overall population and only for a short time window . Our stuThe study was conducted in Rabah Local Government Area (LGA) of Sokoto state and Ardo Kola LGA of Taraba state in northern Nigeria. These LGAs were classified as high-risk for polio transmission, given the presence of large numbers of underserved, nomadic, and hard-to-reach settlements. For advocacy, we visited the immunization authorities, traditional leaders and agricultural extension workers at the state level, and Ardos (nomadic leaders) at the state and LGA levels. The stakeholders were briefed on the planned enumeration of underserved communities . The stuWe held a planning meeting with the LGA immunization and primary health care team, local religious, traditional, nomadic, and village leaders from known remote settlements before starting enumeration and vaccination activities. Other participants included veterinary officials who are routinely involved in providing animal health services to these communities . The leaField teams were comprised of data collectors who were veterinary and agricultural staff and officers; they served as vaccinators and local guides. Local leaders provided the names of field guides who assisted teams in locating the remote settlements in their areas. One field team was assigned to each of the 21 total wards in both LGAs where the fieldwork was conducted. The guides and data collectors received training on conducting enumeration of residents of each settlement, vaccine and cold chain management techniques, OPV vaccination procedures, using Android mobile telephones with global positioning system (GPS) capability, searching methods for additional settlements not included in the harmonized settlement line list, and conducting an active search for AFP cases in the households of the settlements.We conducted this descriptive cross-sectional study, using predesigned settlement enumeration tools and forms  on AndroField guides led the data collectors to listed underserved settlements. Data were collected, using the enumeration checklist tool and GPS Android phones. Data collected for each settlement included GPS coordinates, socio-demographic data of households, the number of children aged <5 years in each household and their vaccination status, the number of children missed during recent SIA, and the number of newly identified AFP cases and their GPS coordinates.The data collection teams used hired vehicles, motorcycles, and canoes as needed to reach hard-to-reach and remote locations. The enumeration teams aimed to visit a settlement one day after SIA vaccination teams were to have visited that particular settlement. LGA Vaccine and Cold Chain Officers provided the teams with OPV, vaccine carriers, and ice packs on a daily basis to administer doses where needed. These field activities were conducted during the May 2013 SIA and lasted for four days. The field teams visited the known and recently discovered settlements, using the harmonized settlement list; they enumerated children aged <5 years and assessed their recent SIA OPV vaccination status by checking their fifth finger on the left hand. Any child found to be unmarked was classified as “missed”, and the child was vaccinated with OPV by the teams.The field teams searched for AFP cases in every household they visited, using the standard World Health Organization case definition for AFP . If a suThe field team held a review meeting with the LGA immunization and primary health care team officers every evening of the SIA and survey to discuss findings, issues, and challenges. Arrangements for vaccines and other logistics for the next day were also discussed.We used a data tool template designed for this assessment and Android mobile devices to collect the data. Any updated line lists of settlements were provided to LGA officers to update future SIA micro-plans with the inclusion of recently identified settlements and groups. Uploaded GPS data were used for mapping nomadic/underserved settlements and AFP cases. Data were analyzed using Microsoft Excel 2007.The National Polio Emergency Operations Centre approved this assessment as a non-research programmatic activity and CDC project determination was obtained. All field activities were conducted with the consent of the LGA Primary Health Care, the community and settlement leaders. The children`s parents or caregivers provided verbal permission to vaccinate their children.Field visits were conducted in all wards of Rabah (11) and Ardo Kola LGAs (10). In Rabah LGA, 77 nomadic or underserved settlements were enumerated, of which seven (9.1%) were missed in recent SIA using the previous micro-plan .The average number of underserved settlements was 7 (range 5-10). A total of 1,296 households with 3,203 children aged <5 years were enumerated. Based on parental recall and no evidence of finger marking for the SIA, 259 (8.1%) of the children counted were missed during the recent SIA, and 115 (3.6%) were never vaccinated through routine immunization or OPV SIAs . The RabThe lack of health and social services for these nomadic and underserved communities is evidenced by the identification of a large number of new settlements that had never been visited for vaccination, large numbers of children missed during recent SIA, and large numbers of children who had never received OPV before by any means. However, the study did not attempt to estimate the length of time for which the settlements were missed. Omar  has arguA large number of these underserved settlements that were identified were missed in the recent SIA, further indicative of gaps in micro-planning. Key factors responsible for these disparities included inadequate micro-planning, limited resources for logistic support, and the lack of community leader engagement in the micro-planning process . The IweOur study in the two LGAs showed that children living in underserved areas and nomadic populations might be missed completely or intermittently vaccinated during polio SIAs due to their frequent mobility and remoteness of their settlements . The nomOverall, 412 (24%) children vaccinated in the scattered, nomadic, and other underserved settlements had never been vaccinated before. Even though a review of primary health care services was not part of our assessment, children residing in the remote nomadic, scattered, and border settlements were likely lacking ready access to routine immunization (RI) services, including outreach. We referred children younger than 12 months in the zero-dose group for RI services and sensitized their parents and caregivers on the importance of vaccination overall and seeking RI services that are typically concentrated in urban settlements. Additionally, constant mobility of nomadic communities further restricts their access to RI and essential health services, and could make efforts to reach them with outreach RI services difficult . Nomads Despite conducting active case searches for AFP, we did not find any missed current AFP cases; in a more extensive endeavour, Gidado et al. found clusters of unreported suspect AFP cases in some settlements . Other sOur findings have limitations. Firstly, our enumeration may have missed some settlements and children because of the remoteness and scattered nature of their households; however, every effort was made to ensure that no child is missed by consulting appropriate community leaders and the search for settlements based on field interviews of settlement leaders was extensive. In the future, a similar exercise could be strengthened by satellite imagery and mapping of enumerated households. Secondly, we were unable to collect socio-economic information of the households and children aged <5 years in the underserved populations. Thus, we could not establish a relationship between lack of vaccination in recent SIA and socio-economic status.By engaging community leaders, a large number of previously unidentified settlements were found with children who had missed polio vaccination. Unvaccinated nomadic children may have contributed to the maintenance and transmission of poliovirus in Nigeria. Sustaining access to this underserved population via SIA and RI activities will increase overall population immunity and prevent poliovirus transmission. Governments should intensify their efforts to involve traditional leaders and non-public health actors such as veterinarians and agriculture officers when planning health services for nomads and other underserved populations.Nomadic and hard-to-reach communities are usually underserved in terms of health and social services;Nomadic children are completely missed or intermittently covered during polio Supplementary Immunization Activities (SIA) due to their frequent mobility and remoteness of their settlements;Most underserved communities are readily receptive to health services, including vaccination.We found a large number of new settlements and households with many children aged < 5 years who have never been reached previously with vaccination services ; all of them were vaccinated during the visits and added to the micro-plans for subsequent polio SIAs;Differences have been noted between wards within the same LGA but also between the two study LGAs in terms of children missed during the recent SIA. The most difficult-to-access wards had the highest number of children missed during the recent SIA and those who have never been vaccinated.


Global vaccination in the face of pandemics such as COVID-19 and new variants is a race against time. Avoiding the opportunity costs of delay and the associated health, social, and downstream economic impacts is a challenge and an imperative. Failures to address the global challenges posed by COVID-19 have become increasingly evident as waves of vaccine-evading mutations have emerged, facilitated by unequal vaccination coverage and diminishing immunity against new variants worldwide. To address these challenges, societal decision-makers (governments) and industry manufacturer interests must be better aligned for rapid, globally optimal trial design, ideally with research coverage, implementation, and accessibility of effective vaccines across joint research, implementation, and distribution cycles to address pandemic evolution in real time. Value of information (VoI) methods for optimal global trial design and risk-sharing arrangements align the research, distribution, and implementation interests and efforts globally to meet head-on the imperative of avoiding opportunity costs of delay and enabling consistent global solutions with maximizing local and global net benefits. They uniquely enable feasible early adoption of the most promising strategies in real time while the best globally translatable evidence is collected and interests are aligned for global distribution and implementation. Furthermore, these methods are generally shown to be imperative for feasible, fast, and optimal solutions across joint research, reimbursement, and regulatory processes for current and future pandemics and other global existential threats. Establishing pathways for globally optimal trial designs, risk-sharing agreements, and efficient translation to practice is urgent on many fronts. With rapidly evolving SARS-CoV-2 mutations and variants, vaccinating populations against the COVID-19 pandemic has been a global race against time –6. Fast,Continuing COVID-19 pandemic waves have resulted in direct acute disease and mortality, as well as long-term repercussions from diminished health system access for other conditions and, more broadly, a decline in the immunity of individuals and populations . CurrentRecent US evidence  shows siUncertainty persists over the duration of COVID-19's effects on the immune system. It is evident that having a strong immune system and being vaccinated  are essential for having the best chance of preventing and combating any sickness, both individually and for populations locally or globally. The opportunity costs of delaying effective vaccine protection during a pandemic locally include a loss in net benefits associated with the failure to stop the pandemic spread and downstream health, health system, and associated economic impacts –18. GlobFirst-generation mRNA vaccines were effective in immunizing against initial COVID-19 variants in 2020  and remain relatively effective with mutations of variants from 2021 and early 2022 (Delta and Omicron) in preventing hospitalization and deaths but not infection , 22, 23.The benefits of new variant-based vaccines, boosters, and related research grow stronger when pre-existing immunity and/or effectiveness of current treatment are suddenly lowered by the appearance of new mutations or variant/s . Most reGiven that rapid mutations arise and proliferate in the most immunocompromised populations –6, the gThe most recent WHO policy has issued an urgent call for governments around the world to examine their vaccination policies and strengthen them in preparation for ongoing COVID-19 mutations and future pandemics. This article focuses on WHO vaccination development, distribution, and population delivery goals . In the Making decisions with uncertain relative net benefit across potentially optimal alternative strategies, VoI methods inform optimal decision making and trial design. They compare the expected value (expected reduced probability of and payoffs from bad decisions or reduced expected loss of perfect information) relative to the expected cost (direct and opportunity cost) of research –33. ImpoApplying VoI methods with appropriate consideration of those contexts systematically enables optimal joint research, adoption, and regulatory investment decisions consistent with maximizing net benefits locally and globally , 35, as In the application of VoI methods before Eckermann and Willan , while tHence, provided trial evidence can be translated, new evidence arising in one jurisdiction is expected to have value in another. Consequently, where prospective VoI from trials across jurisdictions is appropriately considered, additional viable options include using side payments to influence trial design, avoiding fixed trial costs, recognizing the joint value of research, and increasing the strength and implementation of evidence with a large definitive trial. Hence, a combined optimal trial across two jurisdictions improves on separate optimal trials within each jurisdiction. Eckermann and Willan  extend tUnder the non-rival and non-excludable characteristics of a public good, the expected value of a global trial can be summed across jurisdictions. That global value less cost of the trial or global expected net gain (ENG) can then be optimized. Each jurisdiction can make optimal local decisions about whether to adopt or delay a trial as part of a globally optimal trial designed to optimize and share greater global ENG than locally optimal solutions. Notably, a key source of those gains is that global optimal VOI trials overcome the infeasibility of jurisdictions, faced with positive while uncertain INB, to adopt and trial (AT) within the jurisdiction, given the inability to recruit informed patients where they have certainty of new therapy outside the trial setting , 29. Gloj per arm) and hence the global trial size n per arm as a sum of the njs that maximize the global expected value less trial costs: Each jurisdiction can identify whether to optimally adopt or delay and trial (AT or DT) given their prior distribution for INB and local ENG. That is, given their local EVSI of trial dependent on Cr for AT and local EVSI less opportunity cost for DT . As EckeCfj and variable Cvj) of trials incurred locally are shared globally as part of the trial design with globally pooled side payments to ensure optimal DT as part of Pareto optimal and equitable solutions . Direct costs  over time. However, a global trial supports feasible AT and robust evidence of relative effects and NB across treatments to support meaningful specification of future contingencies. Consequently, global trials uniquely enable robust risk sharing .a priori expected to increase the strength of evidence and the future degree of implementation  in allocating samples across jurisdictions ;Avoiding cherry picking and reducing heterogeneity and associated “Frankenstein's Monster” effects arising with multiple trials in evidence synthesis ;Overcoming market failure from free rider effects  and sub-optimal spreading of fixed costs  ;Stronger global evidence is generated to inform regulators and improve implementation within and across jurisdictions , 29; andEnabling feasible and robust risk-sharing arrangements globally to better align societal decision-maker interests and manufacturer interests in avoiding opportunity costs of delay for jurisdictions who AT as part of the global trial .The advantages of optimal global VoI trial design  and riskWith significant opportunity costs of delay;Needing the best and most translatable global evidence; andRequiring global risk-sharing arrangements to reinforce alignment across industries and governments for fast global distribution and the implementation of optimal strategies.Collectively, those advantages are key to addressing COVID-19 vaccination challenges and finding feasible and optimal global solutions for pandemics or similar global problems :Proposed methods generate the best globally translatable evidence and avoid opportunity costs of a delay from research to global translation, distribution, and implementation in practice , 29, 34.Global evidence and translation covering different vaccine variant combinations are required both currently and in real time for future mutations, given immunity imprinting and likely need for vaccines targeting only novel spikes in new variants –27, 46. Globally optimal trial design and risk-sharing agreements align with the research and implementation interests and efforts of countries and vaccine manufacturers globally for doing what is necessary to combat the pandemic and avoiding opportunity costs of delay across all countries while obtaining the best global evidence. Fast, effective global vaccine coverage is key to building global immunity and preventing new variants and their health, social, and economic impacts, especially given that new mutations and variants develop and thrive in immunocompromised populations and are quickly spread in the globally connected world and economies of the 21st century  and industry's interests in vaccine trial design and their global implementation, distribution, and access across joint research, implementation, investment, and regulatory cycles [By lowering the opportunity cost of delay for globally translatable evidence into practice, these strategies aim to maximize global community net benefit and align societal decision-making (governments) and industry (manufacturers) interests toward that objective;In mutually supporting the globally optimal trial design and risk-sharing arrangements, the net benefit correspondence theorem , 52–56 uA question that naturally arises is, “How far can the framework for optimal global trial design and risk-sharing arrangements be extended?” This question has been previously addressed generally for optimal joint research, reimbursement, and regulatory decision-making , 35. NevNo country is safe or immune from the COVID-19 pandemic until new variants of concern are prevented from arising in immunocompromised populations; we have become globally immune to recent variants. As Fontanet (This article has highlighted that optimal global trial design  and riskThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The author confirms being the sole contributor of this work and has approved it for publication.


This supplement also delves into how malaria surveillance is effectively being transformed into a core intervention, describes examples of how routine data can be used to guide programming of malaria interventions across varying transmission settings, and details its critical importance in the “COVID-endemic” context. Articles in the Journal supplement review malaria surveillance system components, provide a conceptual framework for effective surveillance systems, outline methods and provide case studies for assessing malaria surveillance system strengths and identifying gaps, discuss ways to leverage existing services  for a more robust surveillance system, and highlight the importance of country leadership and ownership for effective and sustainable malaria surveillance. Effectively transforming malaria surveillance into a core intervention requires global leadership and collaboration among national programs; but, more importantly, needs the dedication and empowerment of subnational and local leaders. A fully operational surveillance system that effectively links data quality, data use, and data-to-action components will ultimately lead to a resilient and robust system capable of responding to all malaria transmission contexts, and will facilitate improved malaria control and eventual malaria elimination.To articulate timely data-informed actions in routine programs effectively, it is necessary to sync and optimize the use of routine malaria information reported through different systems, such as those generated by outpatient departments, antenatal care programs, community health workers, and the private sector; adapt the granularity of the data to local needs ; invest in effective data-to-action frameworks through clear governance and coordination mechanisms; and promote adaptive surveillance to respond to evolving global threats  and changing external factors. The articles in this


Together with the Africa Continental Branch of the International Society of Paediatric Oncology (SIOP Africa), the Uganda Cancer Institute, a tertiary governmental institution for specialised cancer care services, research and training, hosted the 14th continental meeting of SIOP Africa from the 16–18 March 2022. Under the conference theme, ‘Innovate for Africa’, the hybrid conference brought together close to 400 international delegates to discuss innovations and experiences, as well as share the latest research in the field of paediatric oncology. The World Health Organisation 2030 Global Initiative for Childhood Cancer provided the main starting point for the conference with a comprehensive pre-conference workshop programme, from multiple stakeholders and organisations and the themes for the plenaries towards improving survival to the main breakout sessions. Delegates discussed various ways of improving outcomes in Africa, despite the challenges faced individually and collectively ranging from education, management systems and treatment guidelines to future governmental and NGO involvement in African cancer care. The main achievements of the conference were various commitments for collaboration, investing in junior investigators, development of registries and systems for improved childhood care on the African continent, while working towards greater access to advanced management options such as targeted therapies and bone marrow transplant services. In March 2022, International Society of Paediatric Oncology (SIOP) Africa held the continental SIOP conference in Kampala, Uganda. The highly successful event, delayed for a year due to the COVID-19 pandemic, brought together colleagues and friends from 33 countries and 3 continents, confirming the desire for the paediatric oncology community to engage in-person. The conference was organised by the Uganda Cancer Institute (UCI), supported by the Ugandan Cancer Society, the Palliative Care Association of Uganda, the Uganda Child Cancer Foundation and the Uganda Paediatric Association. Colleagues from South Africa, Egypt and the USA supported the scientific committee and the organisers of the pre-conference workshops.Since the 2018 launch of the World Health Organisation (WHO) Global Initiative on Childhood Cancer (GICC) aimed at reaching at least a 60% survival rate for children with cancer by 2030 [In keeping with the theme of innovation, this SIOP Africa was the first hybrid meeting to facilitate access to delegates to participate regardless of their location, allowing international experts to share their expertise. A record number of pre- and post-conference workshops were held by colleagues from fields including medical, surgical, radiation oncology, allied health services and civil society. In line with SIOP International and SIOP Africa strategies, many of the educational programmes were aimed at improving content for junior investigators . EchoingThe scientific committee received 140 abstracts from more than 35 countries. The in-person component attracted close to 400 participants from 33 countries, with the majority coming from Uganda, South Africa, Ghana, Ethiopia and Tanzania. Disciplines represented were paediatric oncology, paediatric surgery and neurosurgery, nursing, dietetics, pharmacy, rehabilitation, pathology, social work and psychology. Scholarships were awarded to 123 medical and nursing delegates. The virtual component, generously sponsored by St Jude Global and run by Cvent, attracted 55 viewers.SIOP Africa President Joyce Balagadde-Kambugu referred to the WHO GICC goals in the context of multiple challenges on the African continent, requiring locally relevant and innovative solutions and hence the theme ‘Innovate for Africa’. SIOP Africa is dedicated to developing systems and opportunities in Africa to achieve these goals, including engagement with governments. These innovations should improve access to diagnosis, treatment, supportive and palliative care for children with cancer and ensure the gains made are not lost.SIOP President Kathy Pritchard-Jones commended the paediatric oncology community on their response to the COVID-19 challenges, continuing to apply best practice standards of care with necessary adaptations and collaborating on clinical research studies that improve access to treatment. The topics of the pre-conference workshop, in particular, the adapted treatment regimens, provided an opportunity to discuss the realities of implementing the WHO’s GICC. Good infrastructure and multidisciplinary care are prerequisites for tackling the unmet needs for cancer control, including childhood cancer control. The SIOP President-elect Guillermo Chantada praised SIOP Africa in leading the way in adapting therapies to local resources, addressing specific regional needs and adapting innovations for the advancement of paediatric oncology.The WHO representative to Uganda Yonas Tegegn Woldemariam commented on the difficulty in contextualising African paediatric oncology cases in the 400,000 annual global childhood cancers, because the burden of childhood cancers in Africa is underestimated due to poor coverage of population-based cancer registries. The inadequate capacity for early detection of cancers, including childhood cancers, compounded with limited treatment capacity, are the main drivers of low cancer survival rates in Africa. Reliable and accurate epidemiological cancer data to inform cancer control services delivery with adequate human resource capacity were central to improving national cancer control.The keynote address, ‘The history of cancer in Uganda’, was presented by Charles Olweny, UCI Board Chair, detailing how paediatric cancer services began as lymphoma treatment centres at the Mulago National Referral Hospital where Dennis Burkitt first described Burkitt lymphoma. This centre grew to become the present UCI. The concept of essential oncology drugs in Africa, started in Uganda, has demonstrated that we can improve access to essential cancer drugs in Africa. The concept originated from the essential drugs list, where utilising a limited number of medications, most diseases could be treated effectively. The same principle was applied to chemotherapy drugs such as vincristine, doxorubicin, cyclophosphamide etc. . By ensuJackson Orem, Executive Director of UCI, reflected on the successes of the Uganda Cancer Institute which was mandated by an act of parliament to establish four regional cancer centres and has completed the development of a national cancer control plan. His reflections brought home the importance of government support in the establishment of training programmes for cancer specialists, including paediatric oncologists. UCI, which receives 7,000 new cancer cases, 10% of whom are children, continues to strive to improve clinical and scientific services with the Integrated Electronic Medical Record System, a fully automated radiology unit and laboratory auto-analysers. Jane Ruth Aceng, Minister of Health for Uganda, emphasised the importance of the government in fighting childhood cancer on a continent with low survival rates of less than 30% in many countries. She attributed Uganda’s survival rate of approximately 50% to leveraging resources for cancer control with truly mutually supportive partnership focusing on similar goals.Childhood cancer mortality reflects global disparities in health outcomes. Avoidable deaths from childhood cancers in low- and middle-income countries (LMIC) result from, among others, failure to prioritise early detection, misdiagnoses, lack of access to care, treatment abandonment and treatment delays. Inequities in quality care outcomes for paediatric cancer in LMICs demand urgent engagement of national and regional government structures to accelerate improvement in paediatric cancer continuum of care. The WHO GICC lays out policy advocacy, including childhood cancer policy and plans, for improved childhood cancer care outcomes. The WHO’s proposed technical ‘CureAll package’, includes the creation of centres of excellence; universal health coverage; regimens and roadmaps for diagnosis, treatment, evaluation and monitoring; and a sufficient competent workforce. The three cross-cutting enablers are advocacy, leveraged financing and linked policies/governance. SIOP President Kathy Pritchard-Jones noted that even with the establishment of multiple Paediatric oncology units (POUs) in large countries, all can deliver quality care. She recommended the term ‘Centres of Expertise’ rather than ‘Centres of Excellence’ to avoid discouraging those who have not been classified as ‘Centres of Excellence’, to encourage development of specialist centres, but not to distinguish on the basis of the quality of care rather the level of care.Limited financing for cancer control and early detection remains a bottleneck in LMICs like Uganda. Uganda developed their first Uganda National Cancer Plan (UNCCP), through a wide consultative process coupled with active participation and involvement of various stakeholders. In this UNCCP, a section is dedicated to childhood cancer control, with the main goal to achieve an overall survival of 60% for children with cancer by 2026. Advocacy for cancer control is required in all resource settings, but should be a consolidated effort to avoid fragmented approaches. Stigma towards people with cancer should be addressed as a human rights issue. This may be achieved by involving people with cancer and survivors in cancer control advocacy towards improving advocacy and service delivery. An example of efforts to increase awareness and decrease stigma is the 3C club (Children Caring about Cancer), a peer-to-peer network.Alaa Elhaddad (Egypt) focused on the international application of precision medicine. Opening those increased efforts was needed to develop this modality on the African continent. The challenges of targeted therapy in clinical practice in Africa include high cost, long turnaround time, failure to obtain adequate tumour material, defining pathogenic variants in paediatrics and ethical issues surrounding genetic material. Paediatric malignancies have a relative paucity of targeted mutations and distinct molecular alterations compared to adult cancers, and rational combinations of targeted therapies are required in the universalisation of practice.Jennifer Geel (South Africa) described increasing crowdfunding efforts to afford targeted therapies for individuals in South Africa, suggesting that potential funders be informed of the expected poor prognosis of many of these patients. Pharma-sponsored clinical trials for targeted cancer therapy for children in South Africa may increase access, but care should be taken to protect vulnerable populations and patients.Suzanne Turner (UK) highlighted Africa’s role in the development of targeted therapy for conditions such as lymphomas. The potential unique genetics and biology of lymphoma in Africa are under study in collaborative projects, and efforts are underway to identify existing efficacious drugs with fewer side effects with patient surrogate mouse models. Turner stressed that targeted therapies must be adapted to the environment in which they are administered.Mahmoud Hammad (Egypt) presented chimeric antigen receptor (CAR) T-cells therapy as a viable treatment option in Egypt for children and young adults to achieve remission in relapsed/refractory B-ALL. Barriers to CAR T-cell therapy include resource constraints such as cost, expertise and infrastructure. Modified protocol development and twinning are required to support Africa in the development and implementation of CAR T-cell therapy. Support should be given to this therapeutic modality while financing and developing infrastructure.The panel discussion concluded with the recommendation that more bone marrow transplant specialists should be trained, with the Children’s Cancer Hospital (Egypt) being a viable option as a centre with high volumes .Ugandan WHO Country Representative Yonas Tegegn Woldemariam focused on poor healthcare systems which influence childhood cancer survival. Disasters disrupt healthcare for both patients and healthcare workers. There is a need to advance universal health coverage, address health emergencies and increase government investment, continental cooperation and global partnership for technology transfer and capacity building. The African continent should accelerate the adoption and implementation of childhood cancer initiatives and related tools.Francine Kouya (Cameroon) shared her experience in a conflict zone, stressing the importance of patient follow-up programmes, strengthening multidisciplinary teams and the value of communication for patient safety. In times of crisis, psychosocial support has increased importance to parents, children and healthcare workers involved in childhood cancer care.Access to basic palliative care is still lacking for refugees according to Eddie Mwebesa (Uganda) and a palliative care policy should be implemented to improve the management of refugees with cancer. Provision of food, shelter and education often takes priority over healthcare in refugee settlements, with a negative impact on the survival of children with cancer.Julius Ecuru explored ethical considerations in the management of these vulnerable children, whose treatment may be interrupted or delayed due to visa and working permit applications and lack of resources to pay for medical services. Potential solutions would be for host countries to anticipate special circumstances, prepare for their management, embrace humanitarian holistic care for these children and use technology to help in hard-to-reach areas for the provision of health services.Candida infections were a source of high mortality in haematological malignancies in Egypt [Margaret Lubwama (Uganda) reported high rates of multidrug-resistant bacteria, the main cause of bacteraemia in paediatric haematologic cancer patients with febrile neutropaenia, while Youssef Madney reported that Echinocandin-resistant in Egypt . El-MahaChristin Edan (France) described the successful initiation of a 3-year palliative care programme integrated into POUs in 15 Francophone countries under the auspices of the French-African Paediatric Oncology Group (GFAOP).Both Lily Gloria Tagoe (Ghana) and Mapule Kholong (South Africa) reported low rates of COVID-19 in children with cancer, although Tagoe reported 2 deaths in a cohort of 10 infected patients, while Kholong reported minimal clinical impact on 432 patients tested. Rose Nankinga (Uganda) described the increased rate of late presentations due to the pandemic, threatening to reverse gains made in overall survival, and Karim Assani from the AMCC group indicated that the pandemic increased the difficulties of implementing programmes aimed at improving the survival of patients with retinoblastoma.In Tanzania, pupillary dilatation, high intraocular pressure, shallow anterior chamber and extensively necrotic tumours were associated with histopathological high-risk features in retinoblastoma, according to Neema Moshi, and Nicholaus Benedicto found that Tanzanian parents or caregivers refused enucleation because of their perception towards the appearance of the child after enucleation, low level of education, traditional and religious beliefs and poor socio-economic status.Ernestina Schandorf reported a 5-year OS for nephroblastoma in Ghana for stages 1 through to 4 were 100%, 87.7%, 71.1% and 52.4%, respectively. Sahmima Namugerwa (Uganda) linked higher survival in nephroblastoma to improved pathology reporting, increased intensity treatment and improved access to surgery and radiotherapy.On behalf of the South African Neuroblastoma Working Group, Jaques van Heerden reported that less than half of the patients with high-risk neuroblastoma (HR-NB) are operated on, mostly determined by post-induction metastatic remission rate, with non-standard surgical practices, leading to variable OS. A greater rate of primary tumour resection in HR-NB is advocated to improve survival. Robyn Charlton (South Africa) found that socio-economic factors were not significantly associated with neuroblastoma survival, suggesting that tumour biology exerts an overriding influence on prognosis. Irene Nanyanga (Uganda) demonstrated that palliative metronomic CADo led to longer median survival time.Brenda Mallon for the GFAOP group showed the feasibility of staging and estimating outcomes for Burkitt lymphoma, retinoblastoma and nephroblastoma, according to the Toronto Paediatric Cancer Staging guidelines, in seven hospital-based cancer registries.Richard Nyeko (Uganda) demonstrated the importance of multidisciplinary team meetings in the improvement of brain tumour care in Uganda, while Mwebe Katasi described the capacity to improve the early detection, referral, diagnosis and comprehensive care for children with brain tumours in low-resource settings through innovative collaborations.Chemotherapy utilisation  is suboptimal in LMICs such as Ethiopia. Atalay Mulu Fentie identified gaps and designed interventional strategies at POUs to improve safety. In Ghana, most antineoplastic medicines surveyed were found in the private pharmacies; however, the mean availability across all studied pharmacies was below the WHO target of 80%. Kofi Boamah Mensah concluded that the low availability of medicines at public pharmacies indicates the need for government interventions. Furthermore, Ghanaian community pharmacists play an essential role in the provision of cancer health promotion services. Shauna Aroa (Uganda) audited the UCI chemotherapy safety programme, leading to the establishment of a multidisciplinary team with pharmacist involvement. This allowed formalisation of chemotherapy prescribing and administration, which highlighted the value of paediatric pharmacy input for safety, standardisation and education of staff and patients.A comprehensive overview of paediatric oncology care in Africa from the SIOP Global Mapping Programme emphasised marked disparities between countries. Some countries have highly specialised services, while no paediatric oncology services are present in certain countries, including Mauritius, until recently a high-income country . A long-The nursing track comprised 2 full days of free paper sessions attended by over 80 nurses from more than 30 countries. Nursing training was highlighted by Elianeth Kiteni (Tanzania) due to the heterogeneous training nursing staff receive in paediatric oncology. The SIOP Nursing baseline standards have been introduced in an effort to formalise paediatric oncology nursing training. Joan Nakabiri (Uganda) and Tadala Mulemba  presented the Global HOPE nursing education programme as an example of continued professional education for nurses. Wendy Eyiah-Mensah described the initiation of a specialist paediatric oncology nursing programme in Ghana, a collaboration between partners in the UK, USA and Ghana, resulting in 17 graduates in the first year.Glenn Afungchwi (Cameroon) described 57 topic areas identified for inclusion in a foundation course, including a general introduction to cancer and treatment modalities; chemotherapy administration and side effects; psychosocial support, palliative care and infection prevention; and control. Nurses were involved in the development of five (23.8%) national cancer control plans with specific recommendations for nurses. During the COVID-19 pandemic, nurses were forced to adapt to online training. The ‘Fundamentals in Paediatric Oncology’ programme, developed by the GFAOP nursing group in 2013, evolved into an e-learning format with 10 modules. Continuous weekly nursing education sessions at UCI have improved nurses’ knowledge and attitudes, are sustainable, cost-effective and further multidisciplinary team integration. The Global HOPE programme continues to develop nurse leaders from Botswana, Malawi and Uganda in a year-long programme. Modules include essential nursing leadership skills, high-performance teams, diplomatic communication, strategic management and practice models, and nursing quality care. Paediatric palliative care training of healthcare providers in resource-poor settings has been prioritised, with 52 graduates of an online course run in collaboration with Global HOPE.Invited speaker Marilyn Hockenberry emphasised the use of protective gear as well as the important role played by nurses in cross-checking and confirming prescriptions prior to chemotherapy administration to minimise treatment errors. Enyo Bosumprah described a teaching tool to empower nurses to educate parents on discharge on important issues such as response to fever, take-home medication and treatment side effects. The tool resulted in marked increases in test scores, which may translate to improved patient outcomes.et al and Gategetse et al reported that in-person on-site training was effective for increased awareness on early warning signs of childhood cancer. The Awareness for Burkitt Lymphoma Eradication programme (ABLE+) in Northern Uganda is an example of a successful intervention to increase detection and referral, resulting in a marked increase in referrals of children with Burkitt lymphoma.This track successfully incorporated the presentations from various members of the multidisciplinary team, fostering goodwill and networking. Glenn Afungchwi reported that effective training of healthcare workers on early warning signs of childhood cancer required understanding cultural beliefs and values. Both Nchasi Treatment abandonment remains an obstacle to cure in sub-Saharan Africa, where cost is an overriding reason for abandonment. George Chagaluka  described a comprehensive package to enable parents to complete treatment. Results from a World Child Cancer (WCC) survey indicated that in Ghana, the majority of respondents felt that they would not have been able to access treatment for their child without NGO support, and the most important type of support included financial support for drugs and diagnostic tests.et al suggested that children’s hospitals should incorporate a variety of gaming technology as tools within greater play-based oncology programmes to improve overall coping and psychosocial care for children with cancer. From a study of nurses’ well-being, four interventions were highlighted as areas where nurses need greater support: access to a psychologist, case study meetings to discuss emotional impact of work, greater support and recognition from management and more training in emotional well-being and resilience.Claire Namulwa (Uganda) reported that sustained psycho-social support retained children in cancer care during the COVID-19 lockdown and ensured completion of treatment, highlighting the importance of psychosocial care in adherence and raising survival rates. A study of rural Ugandan adolescents reported fear of death which felt inevitable, fear of dependency and lack of privacy, and fear of being a burden. They expressed the desire to be given the opportunity to make decisions relating to their own care, despite parental opinions that they are incapable. Depression and isolation were common feelings, exacerbated by isolation from peers and mutilating surgeries such as amputations. Adolescents reported that peers questioned their ability to function as sexual beings, and they reported stress due to fear of infertility. A Kenyan study on gaming technology as a method of non-pharmacological pain relief noted that in 75% of the cases, cooperation during procedures was improved. Other outcomes included more engagement with peers and improved coping skills. Chagira Lifetime and academic awards awarded after the conference can be seen in An overview of the workshops and symposia can be seen in 1.The ‘Alliance Mondiale Contre le Cancer’ (AMCC) is an NGO mainly focused on women’s and children’s cancer in LMICs through training, education and research . The AMCGuillermo Chantada (Argentina) discussed different therapeutic approaches according to settings . Didi FaThe workshop compiled an early diagnosis multi-year plan with the agreement of the Ugandan Ministry of Health. Aims included that 1) all teams in attendance develop multidisciplinary care of children with retinoblastoma and organise at least one referral centre per country for conservative treatments to preserve eye and vision in bilateral cases; 2) all teams collect data on a common basis for all cases of retinoblastoma in their respective countries; and 3) all teams advocate for the reduction of the cost for retinoblastoma care because no child should die of a highly curable malignancy, such as retinoblastoma, because of financial barriers.The workshop concluded with an invitation to all teams to participate in the regular webinar every 2 weeks to discuss challenging cases.2.The Civil Society and Parents Symposium attracted 57 professionals and individuals across the continuum of childhood cancer care to discuss initiatives to benefit children’s treatment experiences. Emphasis was placed on patients as the primary reason for discussion of improvements in childhood cancer care, rehabilitation and reintegration of survivors. The theme ‘Nothing for us without us’ sent a strong message that patients and caregivers should be integral to the decision-making and planning of childhood cancer services. Some of the key talking points included getting feedback from families that are taking care of cancer patients, psychosocial issues experienced by adolescents, treatment abandonment, retention in care, psychosocial support for vulnerable children with cancer during COVID-19 lockdown, need for educating healthcare workers on the early warning signs of childhood cancer and national paediatric oncology registries in Africa.The symposium acknowledged the position that childhood cancer care may not succeed without parents and caregivers supporting and providing for the children during the process of receiving care. Attendees from diverse backgrounds were encouraged to address specific gaps according to their skill sets, expertise and passion. As many civil society organisations were formed as a result of individuals and groups who have lived through the experiences of childhood cancer itself, their particular experiences were acknowledged as vital to quality care for children and adolescents with cancer.Recommendations included the need for increased advocacy for budget increment by governments, increased efforts directed at developing or creating an enabling policy environment for childhood cancer care and management and public-private partnerships to accelerate access to care. Suggestions included increased patient involvement, especially cancer survivors, in advocacy efforts and involvement of schools.3.International Society of Paediatric Surgical Oncology (IPSO) [The y (IPSO)  hosted iy (IPSO) . An inspNasser Kakembo (Uganda) highlighted the adaptation of resources to achieve optimal outcomes in surgical management of nephroblastoma. Derek Harrison’s presentation on bilateral nephroblastoma recommended neoadjuvant chemotherapy for at least 6 weeks, or 12 weeks in cases of suboptimal response, followed by bilateral nephron-sparing surgery, if possible, or unilateral nephrectomy with nephron-sparing surgery in the least affected kidney. In cases of nephroblastoma with inferior vena cava extension, the recommendation is to administer neoadjuvant chemotherapy for a maximum of 6 weeks, following which infrahepatic thrombus may be removed safely, while suprahepatic disease requires cardiopulmonary bypass on standby while thrombus is removed from the right atrium.Hafeez Abdelhafeez (USA), a surgeon with experience in both low- and high-income settings, stated that the optimal setup for safe hepatoblastoma surgery is feasible across different settings. Peri-operative optimisation, inflow and outflow control, a parenchymal transection strategy, haemostasis and biliostasis are key steps in mitigation of complications.Hafeez discussed the principles of sarcoma staging, biopsy and management and sound tumour biopsy strategy. Understanding the role of multimodality therapy and neoadjuvant therapy based on tumour biology and anatomy and complete surgical resection with preservation of form and function are key factors to improving sarcoma outcomes.Jed Nuchternon spoke on the principles of neuroblastoma staging and management, emphasising multimodality therapy, indications for resection, extent of resection and operative considerations.A ‘tumour board’ interactive panel discussion took place where the management of five patients was debated. This interactive session proved to be the highlight of the meeting with the principles from the previous talks being put into practice, creating lively debate. The day was very well attended with delegates from many continents and many African countries and allowed old and new friends a chance to catch up and share their experiences, be it anecdotal but valuable experiences or sharing new cutting-edge practices based on latest protocols and guidelines. Due to the unprecedented success of this inaugural meeting, IPSO plans this to be the first of many African continental meetings going forward, and we all look forward to meeting up again in the near future.4.International Children’s Palliative Care Network (ICPCN) [A one-day workshop on children’s palliative care was coordinated by the  (ICPCN) , with ex (ICPCN)  and WCC  (ICPCN) . The int5.International Initiative for Paediatrics and Nutrition (IIPAN), significant advances have been made in improving the education and clinical capacity of nutrition services in Africa, closing the gap on several unmet needs reported by paediatric oncology units in Africa [Approximately 46% of the children with cancer in Africa are malnourished at diagnosis . Malnutrn Africa . To furtElena Ladas (USA) provided an overview of IIPAN activities in Africa and Judy Schoeman (South Africa) described the objectives of the SIOP Global Health Nutrition Workgroup such as advocating for nutrition as an essential member of the management team, increasing nutritional education on the African continent and increasing dieticians and nutritionists in LMICs. IIPAN nutritionists from Cameroon, Tanzania, Uganda and Kenya presented cases relevant to local settings and optimal delivery of nutritional care with limited resources, while paediatric oncologists presented the management of severe acute malnutrition, mechanisms of liver impairment and nutritional management of enterocolitis/pancreatitis. Happiness Ndifon (Cameroon) discussed the role IIPAN played in establishing food supply during COVID-19 lockdown in 2019–2020. In summary, the workshop highlighted important nutrition-related management challenges that need increased attention in the African setting in parallel to building the capacity of nutritionists and dieticians on the continent.6.True multidisciplinary care for children with cancer includes a pharmacist for safe preparation, administration and rational use of anticancer and supportive care medications. In LMICs, frequent stock-outs require precise pharmacy prognostication, ordering and tracking of medications. Pharmacists are critical for safe handling and disposal of medications and educating the medical team about new medications. However, the highly specialised field of Paediatric Oncology Pharmacy is poorly represented in most LMICs .The aim of the inaugural SIOP Africa pharmacy workshop was to increase the involvement of pharmacists in the African paediatric oncology community. The workshop was attended by 31 people including survivors, herbalists, clinical pharmacists, paediatric oncology pharmacists, a clinical pharmacist with bone marrow transplant experience and paediatric oncology nurses. The pharmacy workshop explored the issues of mentoring, continuous professional development, specialisation, involvement in a multidisciplinary team and imparted skills in pharmaceutical care plans, safe chemotherapy administration and research .Talks were given on paediatric pharmacy, off-licence and off-label use of drugs, clinical trials, nutrition, herbal medicines and cancer registries . FriendsPharmacists have a vital role to play in the day-to-day management of cancer in children. The workshop was a call that united pharmacists from all over the continent, with the same goal to provide quality care to children with cancer. It is hoped that the momentum from this meeting will grow to have an important impact on childhood cancer survival rates in Africa.7.International Paediatric Radiation Oncology Society (PROS) [A one-day, online radiotherapy workshop was arranged by the SIOP Africa radiotherapy EXCO representatives, endorsed and supported by the y (PROS) . RegistrTwelve practical talks were aimed at radiation oncologists in Africa who are currently treating children. These included general considerations for treating children, modifications required to treat children in a busy adult radiotherapy centre, how to understand and incorporate paediatric disease-specific protocols, the role/interplay of the paediatric oncologist when treating children with radiotherapy in LMIC, imaging, anaesthesia for radiotherapy, best practice contouring, late effects and disease-specific guidelines for nephroblastoma, medulloblastoma, rhabdomyosarcoma and palliative care. International faculty from PROS and CCLG, based in the United Kingdom and the United States, assisted African faculty with practical talks.The workshop proceeded seamlessly with 46 attendees from not only Africa, but globally. Informal feedback suggested that current challenges were addressed. This is just one example of how COVID-19 has facilitated improved online communication, with additional exposure to a relatively rare sub-speciality.8.The resources to develop AMG in Africa are not fully developed . The AMGThe 62 participants and 14 facilitators were from 22 African countries, 5 European countries and the USA, representing 58 institutions. The disciplines represented  were an example of the multidisciplinary collaboration required to successfully formulate AMGs, and participants left the energetic meeting with renewed vigour to continue this important work on their return home. The participants were equipped with the basic tools to identify available resources, assemble a multidisciplinary team and initiate discussion for the development of tumour-based protocols and clinical research questions.9.Collaborative African Network for Childhood Cancer Care (CANCaRe Africa) is an active multidisciplinary regional network in sub-Saharan Africa [The n Africa –28. It fAt the workshop, the specific goals for the current projects were articulated: the Wilms’ tumour Africa project, ‘SUCCOUR – Supportive Care for Children with Cancer in Africa’ and ‘Zero Abandonment from Start to Finish’. The workshop was attended by site leads and steering committee members of CANCaRe Africa and facilitated by advisory committee members. Goals were articulated in the areas of research and data collection, teaching and education, advocacy, partnerships and capacity building. The goals include were to have over 95% complete data, to have a multidisciplinary symposium on a relevant supportive care topic every year, to strengthen the global alliance for the prevention of treatment abandonment with a focus on out-of-pocket costs for families and to continue to build local capacity with a focus on creating leadership roles for junior faculty. The intent is to publish the goals on the CANCaRe Africa website once finalised and approved by all site leads.The Wilms Africa Phase II study started in January 2020 and is evaluating a revised and comprehensive adapted treatment guideline. In Phase I, end of treatment survival increased from 52% to 69% (p = 0.002) and treatment abandonment decreased from 23% to 12% (P < 0.001) [< 0.001) .The SUCCOUR Phase II study includes a clinical research and nursing component which aims to improve supportive care and the management of fever and neutropenia by implementing and evaluating a local care pathway. SUCCOUR Phase I reported on treatment-related mortality and demonstrated a high mortality of fever and neutropenia episodes and late start of empiric antibiotics, often without obtaining a blood culture [ culture , 31.The ‘Zero abandonment from Start to Finish’ study aims to reduce treatment abandonment to less than 10%. The study includes a clinical research, advocacy and fundraising component to reduce out of pocket costs for families of children with cancer. Previous work supported the significance of preventing treatment abandonment to improve survival and the importance of reducing costs for families to enable them to complete the treatment of their child [ir child .10.The WCC  workshopSumit Gupta (Canada) demonstrated the case for cost-effectiveness of childhood cancer interventions in Ghana. This model, developed by the Policy and Economics Research in Childhood Cancer  unit, shLily Gloria Tagoe provided a Ghanaian perspective on childhood cancer management. She shared the history and major achievements since 2010, including (1) an increase in the number of trained medical, nursing and pharmacy specialists; (2) the development of national treatment guidelines and improvements in supportive care, leading to improved survival of children with some of the GICC-focus tumours; and (3) initiatives to decrease treatment abandonment, such as the establishment of funded family accommodation near the paediatric oncology units. Before the launch of the Ghanaian National Childhood Cancer Strategy, the Ministry of Health announced that drugs for four common childhood cancers would be purchased by the government.WCC efforts to improve outcomes in childhood cancer and the patient experience through strengthening paediatric oncology nursing were presented by WCC board members Rachel Hollis, Glenn Mbah and Ayire Emmanuel Adongo. They detailed components of the nursing education programme from the foundation phase through to training the trainers. A critical achievement was to obtain a commitment by the Ghana College of Nurses and Midwives (GCNM) to establish an accredited specialist programme in paediatric oncology nursing, resulting in the graduation of 17 nurse specialists in paediatric oncology in 2021.11.Systematic development, implementation and evaluation of standardised care practices are essential prerequisites to building a foundation for multicentre clinical research and incorporating these research discoveries into routine care. The recognition that African research is poorly represented on the international stage led the hosts of the first Young SIOP Education Day at the SIOP Africa conference to target emerging researchers on the continent. The event was held in hybrid format, hosted by the University of the Witwatersrand and Texas Children’s Hospital Global HOPE Programme. The theme ‘Standardisation of care as a foundation for paediatric cancer cooperative group research in Africa’ reflected the position that clinical research is a critical driver of quality care, novel therapies and quality of care to cure childhood cancer. Subject experts provided comprehensive reviews of the six GICC index cancers, building on historical overviews of developments in each cancer, with critical insights into latest trends in both high and LMIC settings. An afternoon session covered major points in research methods, with a particularly African flavour, such as ‘Approaches and strategies to integrate clinical research into busy clinical workflows’, which stressed persistent hard work to achieve success in research, and ‘Writing abstracts for presentations and publications’, which emphasised the importance of following simple rules to increase the chances of abstract acceptance at international conferences.12.The GFAOP was founded in 2000 by African and French doctors as a medical association bringing together a network of childhood cancer specialists from 18 countries of the Maghreb and sub-Saharan Africa with a vision that children with cancer in Africa can and should be treated locally by trained staff.The GFAOP workshop entitled ‘Decision-making in the treatment of childhood cancer’ was attended by 14 participants from 8 Francophone countries: Burkina Faso, France, Ivory Coast, Mauritania, Morocco, Niger and Senegal. The objective was to provide skills to assist healthcare workers to decide when to use palliative or curative protocols for patients. This was based on the findings that in Francophone Africa most patients present with late-stage disease. Advanced disease complicates management, leaving limited options for treatment which may render diagnostics and treatment impossible in resource-limited settings.Discussion points included the clarification of the definition of ‘advanced stage’ and ‘late stage’ since it is not related to standardised international staging systems, but can relate to a combination of factors such as tumour volume, metabolic or nutritional status and the degree of tolerance of toxic treatment.Possible solutions included:Category 1: patients presenting with a known poor prognosis or patients with a very poor or no chance of survival ;Category 2: patients presenting with a disease where outcomes have been improved by cellular therapies, targeted therapies or innovative therapies (metastatic neuroblastoma);Category 3: curable diseases focusing on the WHO GICC index cancers.To differentiate between three categories of patients:Category 1: managed with a palliative strategyCategory 2: If possible, refer to a local or international centre where therapies are available. If this is not possible, then category 1 treatment  should be started;Category 3: adapted management guidelines and regimens or standard therapies should be started.Upon admission each patient should be classified in one of these categories and the treatment tailored accordingly:Ethical issues raised by inequality of access to care worldwide and how to communicate with families regarding limited resources were discussed.The final discussions related to the importance of palliative care in LMICs. The number of patients requiring palliative care in LMICs exceeds those in HICs and therefore teams treating childhood malignancies should as a first step set up a palliative care programme parallel to curative strategies. Once management teams gain experience, the number of patients undergoing curative treatment is expected to increase progressively. This strategy should be modulated according to the local setting and the context of resources available in the setting. At the end of the workshop, all the participants acknowledged the importance of a robust classification system to prevent waste of resources that are already limited.Global resources for paediatric oncology are unequally distributed . While cSince the launch of the 2018 WHO GICC, Africa has prioritised the principles of the initiative. Morocco, Ghana and Uganda independently supported greater government involvement at all levels of systems development for childhood cancer care: independent paediatric oncology cancer care plans, childhood cancer registries, securing access to chemotherapy supplies and developing surgery and radiotherapy services.Education programmes were a focus of many free papers’ presentations, reflecting the current need in Africa. Inaugural workshops  and those addressing priority areas  focused on building capacity –38. AfriIn line with the six priority cancers of the WHO GICC, many presentations focused on retinoblastoma, HL, ALL and nephroblastoma, with more challenging tumours like rhabdomyosarcoma and neuroblastoma receiving limited exposure. Similarly, bone tumours and rare tumours received little attention, while multidisciplinary management of brain tumours is still in its infancy in some countries.The GICC should receive greater attention moving forwards in North-South African collaborations . AlthougCivil society  in the African context will play a large role in financing, managing and advocacy towards reaching the goals of the GICC in Africa in partnership with governments. Africa faces unique challenges related to political instability, internally displaced persons, refugees and diseases like tuberculosis and HIV that are largely managed by NGOs, which remain an important link between centres of expertise and the community , 42.The 14th SIOP Africa Continental conference delivered in hybrid mode gave an opportunity to reach more people who may not have attended due to concerns about the pandemic. Delegates were enthusiastic about sharing their experiences and innovative approaches in paediatric oncology after two challenging years of COVID-19. This year’s conference featured a record number of pre- and post-conference workshops, reflecting the excitement at being able to participate in person once more. The conference highlighted the need for greater collaborative efforts to consolidate resources for improved childhood cancer outcomes and increased involvement of government to support efforts to achieve the WHO 2030 GICC goals. Whether countries have been officially named as WHO focus countries in the GICC movement or not, the commitment to alignment with these goals was evident in plenary sessions, free papers and discussions. The latest conference of SIOP in Africa rekindled enthusiasm in a depleted but ultimately resilient African paediatric oncology community.AMCCAlliance Mondiale Contre le CancerBLBurkitt lymphomaCARChimeric antigen receptorGFAOPFrancophone African Group of Paediatric OncologyGICCGlobal Initiative on Childhood CancerGNIGross national incomeHLHodgkin lymphomaICPCNInternational Children’s Palliative Care NetworkIIPANInternational Initiative for Paediatrics and NutritionIPSOInternational Paediatric Surgery OrganisationLMICLow- and middle-income countriesPOUPaediatric oncology unit(s)PROSPaediatric radiation oncology societyRTRadiotherapySIOPInternational Society of Paediatric OncologyUCIUganda Cancer InstituteUNCCPUganda National Cancer Control Programme PlanWCCWorld Child CancerWHOWorld Health OrganisationThe authors declare that they have no conflict of interests.Funding for the publication of this report was provided by the Paediatric Oncology Department, Antwerp University Hospital, Antwerp, Belgium.


Improving funding models and implementing policies that facilitate greater interprofessional collaboration and integration at the primary and allied health level could improve the ongoing quality and safety and future sustainability of the wider health care system by reducing inefficiencies and inequalities. Defining these key health care funding–related models, policies, and concepts, identifying research gaps, and systematically mapping the associated literature will inform future research on this topic.The aim of this scoping review is to provide a descriptive overview of contemporary health care funding models and the key policies involved in the delivery of primary and allied health care. Further, it will investigate the impact these models and policies have on interprofessional collaboration and integrated service delivery at the primary and allied health care levels.A search of published and grey literature will be conducted using the following databases: the Allied and Complementary Medicine Database, CINAHL, Embase, Emcare, MEDLINE, PsycINFO, Scopus, Open Access Theses and Dissertations, and Web of Science. The search will be limited to resources available in the English language and published since 2011. Following the search, an independent screening of titles and abstracts will be undertaken by 2 independent reviewers, with a third reviewer available to resolve any potential disagreements. Full-text resources will then be assessed against the inclusion criteria following the same process. Extracted data will be presented using a convergent narrative approach, accompanied by tables and figures.Electronic database searches have retrieved 8013 articles. The results of this scoping review are expected in May 2022.The findings from this review will be used to inform future research projects investigating the role of primary health care funding, interprofessional collaboration, and service integration in improving health care access, efficiency, effectiveness, and sustainability.DERR1-10.2196/36448 According to the World Health Organization (WHO), to meet current and predicted future global health care needs, governments and health care funding bodies worldwide must prioritize health care funding models and policies that embrace universal health coverage (UHC) -4. HealtInterprofessional collaboration, by definition, uses the collective knowledge and expertise of 2 or more health care professions working together to offer more appropriate, timely, comprehensive, and person-centered health care to consumers ,8-12. InSince 1978’s Declaration of Alma-Ata, which was more recently renewed and ratified with 2018’s Declaration of Astana, the WHO has strongly endorsed commitments to increase health care funding and improve funding models and policies at the primary level -15. A grHowever, despite many varied and concerted international efforts to commit to UHC goals and improve primary health care funding models and policies ,4,6, priSince the beginning of the COVID-19 pandemic, existing health care inequities embedded within contemporary funding models and policies have become increasingly apparent . In someAlthough these issues present substantial challenges to global economic and health systems, they also offer governments a unique window of opportunity to rethink health care funding models and policies. By reorienting health systems to better reflect the fundamental values of UHC as part of the pandemic recovery process, there is potential to instill greater ongoing financial and workforce sustainability . HoweverA preliminary search of MEDLINE, CINAHL, Open Science Framework, and JMIR Research Protocols identified no current or in-progress reviews focusing on the role of health care funding in relation to interprofessional collaboration or integrated health care. Instead, previous works have considered the impact of reimbursement systems on equity in access to primary care, the quality of primary care , and intHow do health care funding policies and models impact interprofessional collaboration and integrated service delivery in primary and allied care? The secondary research questions are as follows:Which key health care funding models and policies determine health care funding in primary and allied health care?Which key characteristics of interprofessional collaboration and integrated health care have been researched in relation to health care funding in primary and allied care?What impact does funding have on professional roles and responsibilities when working in an integrated primary or allied health care role?The proposed scoping review will be conducted in accordance with the JBI Institute methodology for scoping reviews -24 and wThis review will consider literature pertaining to adults  who are employed within the specified primary and allied health care disciplines or are the recipients of care provided by these disciplines. For the purposes of this review, primary health care professions will include physicians, physician assistants, nurses, and allied health professionals identified as working in primary health care settings. There is no international consensus on what constitutes allied health or the specific professions and disciplines included within the allied health field . TherefoTherefore, the allied health professionals selected for inclusion in this scoping review are audiologists, chiropractors, dietitians, exercise physiologists, hand therapists, myotherapists, occupational therapists, optometrists, orthoptists, orthotists, osteopaths, physiotherapists, podiatrists, prosthetists, psychologists, rehabilitation counselors, social workers, and speech and language therapists. The following 3 concepts will be explored in this scoping review: health care funding, interprofessional collaboration, and integrated service delivery. Regarding health care funding, factors of particular interest will include health care funding models  and health care funding policies . Health care funding characteristics are also of interest. These will include units of funding , funding principles , the timing of funding , and funding modes  .The elements of interprofessional collaboration addressed by this review will focus on the relationships, interactions, and collaborative processes between primary and allied health clinicians  ,9-12,18.This scoping review will consider health care funding policies and funding models operating at the primary health care level only. The primary level was selected as it has long been stipulated that improving health care funding and implementing policies that facilitate greater interprofessional collaboration and service integration between primary and allied health care at this level could improve the ongoing quality and safety and future sustainability of the wider health care system ,8,14-17.All classifications of primary studies inclusive of quantitative, qualitative, and mixed-methods designs will be considered for inclusion. In addition, grey literature  will also be considered. Due to feasibility constraints, the scoping review inclusion criteria will be limited to digitally available contemporary literature accessible in the English language . A contemporary period of 10 years (from 2011 to 2021) was selected for this review to capture the increased interest in health care funding models and policies post economic recovery from the global financial crisis between 2007 and 2009 .The search strategy will aim to locate published and unpublished literature. An initial limited search of MEDLINE and CINAHL identified relevant articles and the index terms were used to develop a search strategy for MEDLINE (Ovid), with input from a professional research librarian . The seaA search of published literature will be conducted using the following electronic databases: Ovid , EBSCOhost (CINAHL), Scopus, and Web of Science. Sources of unpublished studies and grey literature to be searched will include GreyLit, Google Scholar, Open Access Theses and Dissertations, ProQuest Dissertations & Theses Global, Public Affairs Information Service Index, the WHO, and government health departments of primarily English-speaking countries .Following search strategy implementation, the literature will be collated and uploaded into EndNote version X9  for the removal of duplicate entries. Citations will then be exported to Covidence , for screening of the titles and abstracts. Screening will be conducted against the inclusion criteria by 2 independent reviewers, with a third independent reviewer available to resolve any potential disagreements. Literature that the reviewers agree has met the inclusion criteria in the initial round of screening will be retrieved in full text and assessed against the inclusion criteria by the same independent reviewers, noting the reasons for any exclusions. The final search results (including reasons for exclusion) will be reported in full and presented using a PRISMA-ScR flow diagram .A total of 2 independent reviewers will use a custom data extraction tool developed by the authors to extract data from the included studies. Data for extraction  will incAlthough not a requirement of scoping review methodology ,23, we dArticle informationAuthor(s)DateCountry of originAims or purposeResearch methodologyFunding model characteristicsFunding type, level, unit, principle, timing, and modeInterprofessional collaboration and service integration characteristicsType and purpose of interprofessional collaboration and service integrationPractitioner characteristicsNumber and disciplines of primary and allied health care professionalsFindingsKey findings related to how health care funding policies or characteristics impact interprofessional collaboration and service integrationLevel of evidence and quality ratingLevel of evidence and quality rating will be performed using the Research Evidence Appraisal Tool and Non-Research Evidence Appraisal Tool .Critical appraisal scoreCritical appraisal will be performed using the Crowe Critical Appraisal Tool Form (v1.4) .Due to the broad nature of the research questions and the descriptive purpose of this scoping review, considerable heterogeneity of the literature is expected. It is anticipated that data presentation and analysis will need to accommodate for heterogeneity in the following factors:Research methodology and approaches Funding model characteristics Funding policy characteristics Interprofessional collaboration and service integration characteristics Health care practitioner characteristics To meaningfully account for this complexity in the literature and provide a clear and accurate map of the evidence, a descriptive narrative analysis method of translating the research findings is proposed. Based on the 4-element convergent narrative synthesis framework outlined by Popay et al , a modifThe preliminary analysis will be conducted at the data extraction stage of the review. It will entail organizing and presenting the extracted data  in tabulElectronic database searches were conducted in November 2021, and 8013 results were retrieved. Title and abstract screening, full-text screening, data extraction, and manuscript completion are expected in May 2022. Upon completion of the final manuscript, the scoping review is intended for publication in a peer-reviewed academic journal.The findings from this review will identify the extent and nature of evidence regarding health care funding and how it impacts interprofessional collaboration and service integration at the primary and allied health care levels. These findings will be used to inform future research projects investigating the role of primary health care funding, interprofessional collaboration, and service integration in improving health care access, efficiency, effectiveness, and sustainability.


Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI). Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases. This guideline provides a comprehensive review and then synthesizes the main practical guidelines for the diagnosis of VCI not only for neurologists but also for other professionals involved in the assessment and care of patients with VCI, considering the different levels of health care  in Brazil. We aimed to update practical recommendations for the identification, classification, and diagnosis of VCI. There are currently several updated guidelines and consensuses on the topic, many of which are cited and discussed throughout the text, so it was not our objective to carry out a new systematic review or exhaustive classification of the evidence.Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases until June 2021, using the descriptors “vascular cognitive impairment” or “vascular dementia”. We selected mostly articles published in the last 10 years, but older relevant publications were also included. Articles in English, Portuguese, and Spanish were reviewed. We also revised the reference list of the articles for relevant additional references. Review articles were also included when applicable.),,,19,,,-,,,,(Studies with post-stroke patients have detected VCIND in 24 to 70% of cases),19,. Classic metabolic and cardiovascular RFs are hypertension, diabetes, dyslipidemia, atrial fibrillation, previous stroke, metabolic syndrome, obesity, glucose intolerance, elevated homocysteine, carotid stenosis, and hyperuricemia. Toxic RFs include alcoholism, smoking, and other causes such as low education, sedentary lifestyle, inadequate diet, sleep apnea, and depression)- and hemorrhagic lesions , which present in a variable way, with no single neuropathological lesion characterizing VCI. In addition, there are no widely accepted criteria in relation to the location and number of lesions necessary for the neuropathological diagnosis of VCI)-,,,,, for the diagnosis of non-dementia presentations),9,(1),, magnetic resonance imaging (MRI) are not inherent features of normal brain agingWhite-matter changes - especially symmetrical bilateral punctiform lesions, located in periventricular and deep subcortical regions - are commonly found in healthy elderly subjects),,, the lesion load, the speed of infarct recurrence and the “allostatic load” (which refers to the cumulative effects of multiple vascular RF) is needed. The idea that broadly available therapeutic interventions may effectively participate in the primary prevention of symptomatic VCI emphasizes the importance of more studies aiming at the characterization of this stage),- suggested a novel nomenclature, which was endorsed by the 11th edition of the International Classification of Diseases (ICD-11) ,,7-(9)---66- from mean normative values),,,, and severe functional disability, including difficulties to perform instrumental or basic activities of daily living),9,,. Awareness should be raised to this diagnosis when alopecia and spondylosis are detected along with the typical signs and symptoms of CADASILAmong genetic syndromes, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), caused by mutations in the ),, physical examination , neuropsychological assessment , functional assessment, neuropsychiatric evaluation, and diagnostic exams  9,,-,-, may be useful),95- 98, and the Canadian Stroke Network established a working group to define criteria for VCIBased on all the above data, this panel recommends the use of screening/cognitive assessment tests for the detection of VCI according to the level of health care in which the patient is inserted .The use of the Clinical Dementia Rating scale (CDR) presents some difficulties for cases of vascular nature, although the scale has been validated for such cases in the Brazilian settingsA study of subcortical VCI (70% of cases with CDR 0.5) showed, in cases of moderate and severe subcortical lesions, that the sum of the “functional” boxes  (CDR FUNC) of the CDR presented correlation with the Pfeffer’s Functional Activities Questionnaire (FAQ), CLOX 2, working memory and abstraction of “community affairs”, “home and hobbies” and “personal care” No laboratory test or biomarker is specific for VCI. Conversely, routine exams can assess comorbidities or RF for cognitive decline. Evaluation of blood count, serology, glucose levels, B12, thyroid, kidney, and liver function, is often required - as detailed in a specific article of the present consensus. A metabolic profile with cholesterol and triglycerides is also important. AD biomarkers  in the CSF may play a role in selected cases when the presence of mixed pathology is questionable, lesions resulting from small vessel diseases . Cerebral hemorrhages  can be well visualized through computed tomography (CT) ,, analyzing studies that assessed lesions qualitatively (WM lesion extension) and semi quantitatively (number of lacunes), showed the presence of moderate to severe vascular lesion loadependymitis granularis) and axonal demyelination may be related to PVWMThe application of visual scales can help the clinician in the differential diagnosis, in the anatomical-clinical correlation, especially with cognitive alterations, as well as in therapeutic monitoringMRI can offer advantages in observing PVWH and DWM through T2 and FLAIR sequences; conversely, both CT and MRI seem to identify cortical and lacunar infarcts in a similar way),(118.The finding of lesions caused by multiple infarctions can direct clinical investigation towards the occurrence of coagulopathies, infectious and parasitic diseases, alcoholism, and heart failureIn conclusion, the evolution of the VCI concept from preclinical stages to VMCI and VD turns diagnostic assessment into a challenge for the multidisciplinary team. The patient with suspected VMCI should be evaluated from primary care by general practitioners, with complementary work up being carried out at the secondary and tertiary levels in a horizontal manner, according to the need for more advanced instruments, particularly advanced neuroimaging techniques.


Adolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal–associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross–sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics in adolescents.In 193 participants  enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals  in multiple biological media  and acquired resting–state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency  in 111 brain areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models to examine association between metal mixtures and each graph metric (GE or LE), adjusted for sex and age.We observed significant negative associations between the metal mixture and GE and LE . Lead and chromium measured in blood contributed most to this association for GE, while chromium measured in hair contributed the most for LE.Our results suggest that exposure to this metal mixture during adolescence reduces the efficiency of integrating information in brain networks at both local and global levels, informing potential neural mechanisms underlying the developmental toxicity of metals. Results further suggest these associations are due to combined joint effects to different metals, rather than to a single metal. Exposure to neurotoxic metals and their impact on the brain is a growing worldwide health concern . Metals a priori selected brain regions associated with early life exposure to individual metals   provides insight into the mechanisms linking metal exposure and alterations in brain functions . In partnganese) . Our datTo investigate the impact of metal exposure on the brain, it is critical to consider not only single metal exposures but the mixture of co-occurring neurotoxic metals . HistoriIn this study, we investigate how metal exposure impacts brain network properties in adolescents. We use graph theory metrics to quantify how the brain integrates globally (GE) and locally segregates (LE) information and assess associations between these metrics with metal mixture exposure. To define our metal mixtures, we measured concentrations of four metals  in four biological media  from 193 adolescent participants living nearby ferro-manganese industry/alloy plant activity in northern Italy enrolled in the Public Health Impact of Metals Exposure (PHIME) study. Then, using weighted quantile sum (WQS) regression, a statistical method commonly used to assess the impact of chemical mixtures on various health outcomes , we examThe Public Health Impact of Metal Exposure (PHIME) cohort investigates associations between metal exposure from anthropogenic emissions and developmental health outcomes in adolescents and young adults living nearby the ferro-manganese industry in northern Italy. Details of the study have been described elsewhere . InclusiWritten informed consent was obtained from parents, while participants provided written assent. Study procedures were approved by the Institutional Review Board of the University of California, Santa Cruz and the ethical committees of the University of Brescia, and the Icahn School of Medicine at Mount Sinai.Biological samples including venous whole blood, spot urine, saliva and hair were collected from each subject upon enrollment, as described in detail in previous studies . Complet3). Fifty contiguous oblique-axial sections were used to cover the whole brain where the first four images were discarded to allow the magnetization to reach equilibrium. For each subject, a single 10-min continuous functional sequence using a T2*weighted echo-planar imaging (EPI) sequence  was acquired. During resting-state scans, lights of the MRI room were off and participants were instructed to stay awake, relax and daydream (not think about anything) with their eyes open. They were presented with an image of a night skyline figure projected on a MRI compatible monitor. Padding was used for comfort and reduction of head motion. Earplugs were used to reduce noise. Data were read by a board-certified radiologist to determine quality and possible incidental findings–no findings were reported.Magnetic resonance imaging (MRI) and functional MRI (fMRI) data acquisition was performed on a high-resolution 3-Tesla SIEMENS Skyra scanner using a 64-channel phased array head and neck coil, at the Neuroimaging Division of ASST Spetali Civili Hospital of Brescia. For each participant, a high-resolution 3D T1-weighted structural scan was acquired using a MPRAGE sequence , Brain Connectivity toolbox  and custFor each subject, the structural magnetic resonance image was co-registered and normalized against the Montreal Neurological Institute (MNI) template and segmented to obtain white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) probability maps in the MNI space. FMRI data were spatially realigned, co-registered to the MNI-152 EPI template and subsequently normalized utilizing the segmentation option for EPI images in SPM12. All normalized data were denoised using ICA-AROMA . AdditioBased on the Harvard-Oxford  atlas, 1Global and Local Efficiency (GE and LE) were computed using the Brain Connectivity toolbox  on the dVisual inspection and descriptive statistics  were used to characterize the metal concentrations in different media. All descriptive statistical analyses were performed using R version 4.2.1.To examine associations between our multi-media metal mixture  and graph theory outcomes (GE and LE), we used a WQS-based multi-media biomarker (MMB) approach . Figure This study included 193 participants  living in Northern Italy, with an average age of 19.2 years (range = 15–25). Metal concentrations in the different media are reported in We first examined the association between each individual metal in all media with GE and LE . For allGE = −0.076, 95% CI ; LE = −0.048, 95% CI ; Results from second level repeated holdout WQS analyses revealed associations between the overall metal mixture and GE and LE , and theGE = −0.076, 95% CI ; βLE = −0.048, 95% CI ]. We also observed that urinary lead and chromium contributed most to the association with GE ; while hair chromium contributed most to the association with LE (38%). Overall, our results substantiate previous findings of associations between metal exposure and altered brain connectivity, and further suggest that environmental exposure to a mixture of neurotoxic metals during adolescence reduces the brain ability to efficiently integrate and segregate information, highlighting the need to further study the impacts of environmental exposures in developmental windows like adolescence  approach, we observed a significant negative association between exposure to a mixture of five neurotoxic metals  and global efficiency (GE), with lead and chromium contributing most to this association. Significant negative associations between the metal mixture and both GE and LE were found [βlescence . FurtherOur findings show that urinary lead and chromium were the top contributing metals in the association between the metal mixture and GE, and hair chromium contributed most to the association with LE, suggesting that urine and hair may be critical biomarkers for estimating the effects of metal mixtures on brain connectivity and further, these metals may exert a greater influence on global and/or local functional connectivity across/within topological brain networks. Lead exposure is known for causing the disruption of neuronal activity, in particular to alter the release and storage of neurotransmitters from the presynaptic nerve endings, that may change the developmental processes of synapse formation in children and young adults and results in altered brain functions . Previouvia its neurodegenerative effects , and ultimately neurobehavior and cognition.Using a multimedia biomarker (MMB) approach, we were able to estimate the associations between a complex metal mixture and brain metrics. This method allows us to leverage the complementary information provided by each medium on different biological processes and therefore, to improve the exposure characterization. Our findings that urine contributed most to the associations between both lead and chromium and GE, and hair contributed most to the associations between chromium and LE, suggests that urine and hair may be critical overlooked biomarkers for estimating the effects of metal mixtures on brain connectivity. Given our results, we suggest that future neuroimaging studies on metal mixture exposure aim to collect multiple media, including urine and hair specimens, to explore the effects of metal mixtures on the brain. Altogether, our research supports the notion of adolescence being a timepoint of vulnerability to environmental exposures. More specifically, our results suggest that the adolescent brain connectivity is vulnerable to metal mixture exposures during this period. Given that adolescence is a period of rapid brain development, our results suggest that metal exposure may have the potential to alter neurodevelopment The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Review Board of the University of California, Santa Cruz and the Ethical Committees of the University of Brescia, and the Icahn School of Medicine at Mount Sinai. Written informed consent to participate in this study was provided by the participants or their legal guardian/next of kin.All authors listed in this work have made a substantial contribution to the concept or design of the article, the acquisition, analysis, or interpretation of data for the article, drafted the article or revised it critically for important intellectual content, approved the version to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.