Cancer patients and survivors can experience treatment related side effects that impact nutrition status, as well as unwanted weight loss, weight gain and poor dietary quality. Therefore, they are a group that would benefit from nutrition intervention. A qualitative study was conducted online (six focus groups and two interviews) with 12 oncology providers and 12 survivors in the United States. Participants were asked about the role of nutrition in survivors’ health, appropriate components of nutrition care for cancer patients, and strategies to integrate nutrition into oncology care. Feedback on a proposed program, “NutriCare”, was also sought. Focus groups were recorded, transcribed verbatim, and analyzed for themes. Four main themes emerged: (1) nutrition is an important component of oncology care and source of empowerment for cancer patients; (2) in the NutriCare program, the prescription pad component was viewed as a critical aspect, and there was also a preference for dealing with patients and survivors separately; (3) for implementation, the most appropriate time for providers to talk to patients about nutrition is during the development of the treatment plan. Reinforcement of key nutrition messages by providers was also highlighted; (4) major barriers included lack of time and motivation by providers. Survivors were interested in and providers supportive of integrating nutrition into oncology care. Cancer patients can experience side effects of treatment that can impact nutritional intake ,2, as weThis lack of guidance can lead to nutrition information being obtained elsewhere, often from unreputable sources, or patients may turn to alternative approaches such as supplement use and fad diets, often unsupported by scientific evidence . PreviouTo address this gap, the research team developed the NutriCare program using the 5A model , as a potential program to help providers integrate nutrition into routine oncology care using a patient-centered approach. This paper reports on focus groups and interviews conducted with oncology providers and cancer survivors to gain insight into their views on integrating nutrition into oncology care, as well as their feedback on the content and implementation of the NutriCare program.A nutrition intervention, “NutriCare”, was designed by the multidisciplinary team and utilized in the focus groups to determine acceptability of such an approach. The 5A model recommended by the Centers for Disease Control and Prevention for smoking cessation, with demonstrated feasibility in primary care settings , was adaThe NutriCare program content was developed by the research team between March and July 2018. The model is outlined below, along with the resources that have been developed to support this program.Patients complete a Nutrition Assessment for Cancer Patients (NACP) form that asks patients how often they experience 12 cancer-related symptoms that affect nutritional intake  and assesses adherence to the recommended intake of 11 key food groups on a 4 point Likert scale. Symptoms were chosen from nutrition impact symptoms commonly reported by cancer patients .Prescription pads have been previously used to provide physical activity advice. The nutrition prescription contains seven nutrition recommendations, adapted from the current nutrition recommendations for cancer survivors and the newly released Cancer Prevention Recommendations by the World Cancer Research Fund (WCRF)/AICR with a strong evidence base , includiIn addition, the patient also receives individual-specific advice based on the results of the NACP questionnaire above. For example, if the individual highlights that nutrition impact symptoms are an issue, then they are provided with nutrition advice in this area ,16, whicA section on goal setting is included in the provider toolkit  to help This stage involves the provision of an evidence-based patient toolkit. The toolkit comprises sections on the importance of nutrition for cancer patients and survivors, how cancer treatment can impact on eating patterns, strategies for managing these eating problems if experienced, preventing unwanted weight loss and weight gain, healthy eating and active living post-treatment, and a frequently asked question (FAQ) section split into 15 food groups or related topics, as well as additional information on food safety, how to talk to their healthcare team about their diet, and how to evaluate nutrition information for cancer survivors.Finally, the clinician arranges follow-up visits to reassess the individual’s intake and refill the nutrition prescription pad.To help determine current views on integrating nutrition into oncology care and to obtain feedback on the NutriCare program, a total of six focus groups (three with providers and three with survivors) as well as two structured interviews  were conducted. Convenience sampling was used, as the individuals had previously served as part of a stakeholder panel for the Nutritional Needs of Cancer Survivor Project (Project NNOCS) run by the Principle Investigator (PI). Both healthcare providers and cancer survivors were recruited in June and July 2018 and informed consent was obtained before focus groups were conducted online using WebEx between 12 July and 1 August 2018.All focus groups lasted an hour and were moderated by the lead author (LK), who was trained by an expert in qualitative methodology (SCF). Two separate moderator guides (one for providers and one for survivors) were developed by the lead author and PI with input from the rest of the team. The providers received the healthcare professional toolkit and the 5A model guide to review prior to the focus group, while the survivors received the patient toolkit for review.Providers were asked about their general views on nutrition practice in oncology care, including their current practice and access to evidence-based recommendations, the program content and format, and the feasibility of utilizing the toolkit in practice. Survivors were asked about the nutritional needs of someone who has survived cancer, where information is currently obtained, the content of the patient toolkit, and their thoughts on participating in the NutriCare program. At the end of the focus group, the moderator summarized the main discussion points and asked for feedback to ensure that the participants’ perceptions of key points were captured correctly. All participants received a $25 gift card for their participation.n = 2) were then analyzed using this codebook by the lead analyst and one other member of the study team (IY), both of whom independently reviewed the transcripts and coded the data before meeting to obtain consensus. Any area of disagreement was resolved by reviewing the transcripts. As >80% consensus was agreed, the lead analyst coded the remaining transcripts. Microsoft Excel (version 1908) was used to assist with coding, since the number of groups and interviews was small enough not to require specialized qualitative analysis software. The coded data were then assessed to identify themes relevant to the research question. Supporting quotes for these themes were identified. Themes from both the healthcare professional and the survivor focus groups were similar and were grouped together into four categories: (1) nutrition in oncology care; (2) NutriCare program content; (3) NutriCare program implementation, and (4) barriers and facilitators. These are presented with supporting quotes. Participants’ identities were protected using participant numbers.The focus groups were recorded and transcribed verbatim. Based on the research aims and the questions asked during the focus groups, a codebook was developed by the lead author, who served as the lead analyst. The codebook was inductively refined based on the focus groups and consisted of three main categories: role of nutrition in oncology care, program content, and program implementation. All research team members reviewed and approved the final codebook. A subset of the transcripts .Twelve oncology providers and 12 cancer survivors (survivors of a variety of cancers of varying duration) took part in focus groups, which ranged in size from three to five participants. Two cancer survivors took part in individual interviews due to an inability to take part in the focus groups on the assigned date. Participant characteristics are outlined in Three themes were identified in this category: (1) access to evidence-based recommendations and advice, (2) variability in nutrition provision, and (3) empowerment and control.Both providers and patients reported challenges in accessing evidence-based nutrition recommendations. Both the oncology providers and cancer survivors considered that accessing evidence-based nutrition recommendations was important, and yet accessing these recommendations was a challenge for both, with the exception of dietitians.“I think there’s pretty decent access for me, as a dietitian, am because I know where to look and I know where to go, I know the organizations I like to rely upon, the physicians on the other hand, they probably don’t have the same knowledge of where to go, and establish their go to places to look up information”Healthcare Professional 1—dietitianSurvivors seemed to be vulnerable to misinformation and access to evidence-based guidance was not always readily available. Many reported using the internet to locate this information, particularly when it wasn’t addressed in the clinical setting, and that led them to information that was not necessarily legitimate.“I do know a lot of people aren’t very discerning about how they get their nutrition information, if it’s in writing and in particular if it’s on an infographic they’ll take it as gospel so you know that’s real problem”Survivor 1Oncology clinics varied in providing nutrition guidance to cancer survivors. There was variability in accessing nutrition advice through oncology clinics due to different structures, resources, and locations. Some clinics had healthcare professionals specifically assigned to address behavior change or screen all patients for malnutrition or nutritional deficiencies as a standard part of practice; however, others did not address nutrition nor did they have the resources to provide such information. Some survivors had received dietitian consultations at some point during their care, but many had not.“it doesn’t get much attention from the medical profession at least the people that I dealt with”Survivor 12Lack of nutrition input was particularly noted by healthcare professionals in rural hospitals with smaller teams, although those in larger hospitals also noted a lack of information. Even where the resources were available, they were not always utilized by healthcare professionals. In some cases, they were also not utilized by patients due to the large number of appointments they already had in addition to chemotherapy, on top of which adding a nutrition appointment did not seem feasible.“With the large cancer hospital that I’ve been associated with, they don’t emphasize it, and then with that people are left on their own and you know it’s not emphasized there is so much going on in cancer experience that it often left to the wayside and not dealt with”Survivor 3Cancer survivors considered nutrition to be a tool for empowerment and control. Cancer survivors considered nutrition to be a tool that could empower them and give them control over an aspect of their care at a time when decisions seemed to be made by others (the oncology team). The nutrition aspect of their care provided a sense that they were taking back control of their bodies again.“Patients are looking for something that they can help themselves with that’s not one more chemical that they’re putting in their body, how else can I help myself a different way.”Survivor 9“It is the one aspect that they have control over and they are in charge of so I think that gives them some incentive to follow through because we can’t do it for them, they’re doing it for themselves.”Healthcare Professional 7—dietitianThere were two emerging themes in this area: (1) the prescription pad component was viewed as a critical aspect of the program and (2) an awareness that the needs of patients and survivors are different and should potentially be more clearly divided in this program.The prescription pad was viewed as a critical aspect of the program. The prescription pad seemed to carry a lot of weight and there was a perception that if a clinician were to provide advice in this form it would be more likely to be taken seriously and to be implemented. It was viewed as more than just a piece of paper. It was clear that clinicians have a lot of power in this setting and that recommendations from them would be trusted, with all survivors wanting to hear this from their clinicians even ahead of nutrition experts such as dietitians.“I like this nutrition prescription pad, I’ve had good luck when you get a survivor to commit to a health goal and you sort of write a contract about it and this is essentially giving something and you’re going to have a discussion about specific goals, so I think that this can be very impactful.”Healthcare Professional 4—oncologist“If a healthcare provider writes a nutrition prescription, it’s hard to ignore, you know somebody else from your circle can assess the intake and weight status but the oncologist writes a nutrition prescription that’s something you have in hand that you access, so it would have some weight to it I believe.”Survivor 3In regards to the differing needs of cancer patients and survivors, many of the healthcare professionals and survivors showed a preference for splitting the resource into two separate tool kits—one for those undergoing active treatment and one for those who have completed active treatment and who could focus on dietary quality and weight management. However, some still liked to have all the materials in one place and likened it to a manual for a car, where one can go to the relevant sections but still have a comprehensive resource. Some of the questions in the NACP, such as how many portions of fruit they consume per day may not be as relevant during active treatment and is not something that would specifically be addressed at that point. Therefore, further refinement of the questionnaire to reflect the differences between patients and survivors was recommended.“I like the fact that it sets up to be both symptom management and survivorship.”Survivor 7Four main themes emerged that focused on implementation of the program: (1) the role of the HCP should be to champion the program; (2) a need for flexible training and guidance regarding the program content; (3) the best time to implement was deemed to be post-diagnosis, in line with the development of the treatment plan; and (4) reinforcement of key messages and the benefit of small changes should be encouraged throughout.The healthcare professional’s role should be to champion the program. All participants felt that to be adopted, doctors would need to initiate and champion the program. Dietitians highlighted the potential impact of this, noting that consultations went better with individuals who had received a few minutes talk from their doctors highlighting the importance of nutrition before a referral to them. After a referral to the program, a dietitian or nurse could then deliver the additional components, and this could be dictated by the clinic structure and resources.“I think it’s fantastic and I think doctors they still have a lot of power, a lot of respect and a lot of power, especially when someone tells you you have cancer and I think they are the most important piece of the puzzle, I think if doctors start this process…”Survivor 1Flexible training and guidance will be required. A need for training was recognized by the healthcare professionals who felt that this would enable anyone to deliver the intervention. It would also address the lack of confidence that many of the non-dietitians felt in their ability to deliver a nutrition intervention, when many had not received specific nutrition training and were not confident they could deal with follow-up questions. They preferred a brief, on-line training format that would fit into busy clinic schedules, with units that could be referred to when needed. Not all healthcare providers were confident in delivering behavior change interventions or developing SMART goals, and they wanted these to be incorporated in the training as well. Dietitians also felt that training would be useful, as they did not always have specific training in oncology or certain aspects of oncology, e.g., survivorship versus acute care. Survivors highlighted a need to receive guidance on how to best use the survivor toolkit and determined this should take place in person with a healthcare professional, an aspect already part of the NutriCare program.“I think training would be very beneficial because we can read and we can absorb but you know the fact that people would maybe ask the question I wasn’t prepared to answer would be I think training would be beneficial…”Healthcare Professional 6—dietitianThe best time to implement the program is alongside the treatment plan. Participants reported that patients at diagnosis are dealing with a lot and that this would not be an appropriate time to start the program, although some survivors did mention initiation at this point. The majority felt that introducing the idea of nutrition briefly at this point would be more effective, and then when the treatment plan is decided, the nutrition program should run in tandem with it and it should continue as part of the survivorship plan for it to be taken seriously and to work.“I think it’s a waste of time to try to discuss something like this during diagnosis because nobody will hear what you say and over my head I would not care and it would be waste of time. I think during treatment is the time to start approaching these issues”Survivor 12“Then it should just be ongoing, there should be no end to the nutrition part, it’s not something that’s temporary”Survivor 1Reinforcement of messages and the benefit of small changes should be encouraged throughout. Reinforcement of the key nutrition messages emerged as a strong theme, with the aim of making the behaviors ingrained and habitual. Participants felt that it was important to have the messages continually reinforced in multiple ways by their oncology team. Patients would also need to continue asking for nutrition advice, care, and guidance.“[The] message has to be repeated many times especially in a cancer situation where sometimes you only take in 10 or 15 percent of the information in an appointment, so I like the toolkit. But we have to somehow get it repeated whether its oncologist, nurse practitioner, dietitian, support group, care givers, it has to be out here, you know, use your seatbelt, or don’t drink and drive, how many times have you to hear the message before it becomes automatic and that’s key”Survivor 3The idea of small steps to behavior change was also very strong, especially in the face of the physical and mental challenges that oncology patients face. Participants believed that the benefit of small steps should be made very clear to the patient/survivor.“And maybe just an overriding sense that this whole process of changing your lifestyle habits and changing what you eat is really difficult it’s not going to be easy, and so no one get a sense of you know ‘why can’t I do this?’ It’s so incredibly hard, because it is.”Survivor 10Barriers such as time and language and facilitators, namely interest and infrastructure, were mentioned when the participants considered implementation of the NutriCare program.The main barrier to implementing this program was time constraints. It was recognized by survivors and healthcare professionals that clinicians did not have time in busy clinics to deliver this program, and that they would not be motivated as they would not be reimbursed for their time.“I don’t think this will happen in practice because the physician is too busy and is not paid for a nutrition visit”Healthcare Professional 1—dietitianThe hospitals included in the focus groups serve a multicultural cohort and require all materials in a variety of languages. Since the toolkit is available only in English, this could serve as a barrier in some clinics.All participants however, recognized that nutrition is an important part of oncology care in terms of quality of life and survival, and something that they would like to have incorporated into oncology practice.“It seems to fit hand in glove with survivorship. It’s like, in sports you try to do everything you can to prepare for an event. Seems like to me, you try to do everything you can to prepare for survival.”Survivor 3Overall, there was a great interest in the NutriCare program and a consensus that it not just educated patients and survivors, but also the healthcare professionals themselves. The usability of it and the concise summary of current evidence and practical tips were lauded by both groups. In situations where there is no access to dietitians or nutrition advice, it was deemed to be beneficial to provide the toolkit to ensure that nutrition was addressed in some way.“I think you guys have done great work and everything, you’ve summarised a lot of really good information and it’s an excellent resource.”Healthcare Professional 1—dietitian“There are things in there that… had not occurred to me. I learned a lot from reading the toolkit and I thought it was really interesting”Healthcare Professional 8—nurseThere were some clinics that felt that this program would fit well with their current practice and that they had the skills and experience to deliver it and that the resources would be of benefit to this. However, there was an acknowledgement that this would not be the case for all clinics and healthcare teams.“It would outline very nicely with what we are already doing, I don’t think it will override some of our comfort zone to incorporate and I was looking for the resources to help and support healthy living recommendations in a way to motivate patients”Healthcare Professional 11—dietitian“I think in our institution we actually I sent this idea around to a variety of providers and everybody seemed had excited about it; the big thing is to get enough resources to spread them out throughout the cancer center where patients are seen.”Healthcare Professional 12—nurseThis paper outlines the views of both oncology providers and cancer survivors on the integrating of nutrition into oncology care and their views on the use of the 5A model to deliver this. Focus group findings revealed a need and a desire for nutrition information from a reliable source from the survivors, and an interest in and support for the program from both providers and survivors. The most appropriate and feasible time to introduce this program seems to be at the point of development of the treatment plan. The content was viewed favorably, although providers suggested there might be barriers related to time and language. The appropriate role of the oncologist was indicated as that of a “champion” for the program.All survivors indicated a desire for evidence-based information at all points in their journey. Current practices related to the provision of nutrition information are varied, and there is often limited, if any, access to nutritional counseling. Cancer survivors often reported receiving little guidance in this area and expressed an interest in receiving this information from their oncologist or physician where possible . PreviouNutrition is critical to the management of cancer. The detrimental effects of some treatments on dietary intake through commonly occurring side effects ,20, as wNutrition is important from a survivor perspective as it offers survivors control and it is something they can manage, and also gives a sense of empowerment. This was a very clear finding from the qualitative component of this work. By including nutrition as a part of a standard care, survivors may gain a sense of power over a component of their care. This could help to increase the motivation and empowerment of patients and survivors. Motivation plays a large role in the likelihood of an individual creating positive change in their lifestyle and the likelihood of their maintaining this change . Cancer The use of a prescription pad to provide nutrition advice was thought to have potential as an effective way to promote nutrition goals and for providers to be able to champion nutrition as an important aspect of care. Lifestyle prescriptions have previously shown to be effective , most noThe goal of integrating the NutriCare program into current care is to be sustainable. However, it was clear from the results that there may be barriers to this, e.g., time and language. Language could be addressed by providing the resource in additional languages other than English once the pilot work is complete and the program is refined. This program was designed to be implemented by the oncology team; however, it was clear from this work that clinicians see their role as supporting and introducing the program rather than delivering it. The potential for other team members to deliver it varies, with some clinics reporting more of a capacity to do this than others. Any intervention needs to be convenient, fit for purpose, cost-effective, and sustainable, and so pilot work will now evaluate the feasibility of incorporating this program as part of routine care and assess participation, adherence, and retention rates.These findings will help to further inform the development of this program, with the ultimate goal of ensuring that evidenced-based nutrition information is easily accessible to individuals at all stages of their cancer journey and can be implemented in a way that suits both the patient and the medical team. Nutrition is a missing piece in healthcare—doctors prescribe medicines but not nutrition or nutritious foods . A lot iThe main limitation to this work is that the focus groups were conducted with a convenience sample. However, this sample represented the main professions that deal with oncology survivors and that we wanted to include. In addition, they were located across the United States.This study found that survivors were interested in and providers supportive of a nutrition program for cancer survivors. They provided valuable input on the content and implementation of a proposed intervention utilizing the 5A model in a clinical setting. Determining if it is feasible to integrate nutrition care into standard oncology practice is a vital next step, and it is clear that this approach needs to be convenient and sustainable. Pilot work is currently underway to address this question and to further inform the development of the NutriCare program.


We report the case of a 63‐year‐old Caucasian woman with multiple relapsed IgM multiple myeloma (MM) and elevated free kappa light chains (fκLC). Due to hyperviscosity syndrome with visual impairment, regular plasma exchanges were performed. As part of her 11th line of therapy, an experimental protocol consisting of pembrolizumab, pomalidomide, and dexamethasone was initiated. To reduce fκLC and immunoglobulin (Ig) M, we performed immunoadsorption (IA) using columns containing recombinant single domain camelid antibody fragments as ligands. We measured pembrolizumab (humanized IgG4 kappa anti‐PD1 antibody) levels before and after each IA session and found a 98.1% reduction from baseline with five sessions of IA. Comparable elimination kinetics were observed for serum IgG, whereas fκLC and IgM were eliminated to a substantially lesser extent. These findings highlight that in hyperviscosity syndrome due to IgM MM, broad spectrum IA columns might be only moderately effective compared to total plasma exchange or double filtration plasmapheresis. Monoclonal antibodies are efficiently reduced by extracorporeal therapies and re‐dosing is necessary to provide sufficient efficacy. In the case of serious adverse events such as immune‐related adverse events, IA might be used to eliminate the monoclonal antibody. Measuring IgG levels might be a reasonable strategy for monitoring drug levels of monoclonal antibodies during IA. Treatment initiation is indicated when attributable end‐organ damage or myeloma defining events are present. Hyperviscosity syndrome due to high serum paraprotein levels is a rare major complication, most frequently seen in IgM‐related disorders like Waldenstroem's macroglobulinemia. Clinical symptoms such as mucosal bleeding, visual impairment and neurological symptoms warrant emergency therapeutic apheresis to quickly remove the causative paraproteins.Therapeutic apheresis eliminates concomitantly used biologicals. Only a few studies investigated the role of TPE to reduce toxic drugs.2Here, we report the case of a 63‐year‐old Caucasian woman with MM evolving after a 20‐year history of IgM‐monoclonal gammopathy of undetermined significance. The rare diagnosis of IgM MM was established after exclusion of the prototypic Waldenstroem mutation of MYD88 L625P and the presence of myeloma bone disease.Prior therapies did not control her disease. Intermittent TPE was performed since 11 months because of hyperviscosity syndrome  . Between each session, pembrolizumab concentrations remained roughly stable. At the end of the treatment cycle, a pembrolizumab concentration of 0.96 μg/mL was measured, corresponding to a 98.1% decline from baseline.3In our patient, several sessions of TPE were performed successfully, to treat and prevent hyperviscosity‐related vision impairment. On progression, IA was chosen to reduce plasma IgM and fκLC. Rapid relief of hyperviscosity‐associated symptoms was accomplished. However, elimination of serum IgM, the pivotal villain of hyperviscosity, was less effective compared to prior TPE sessions . The observed elimination‐discrepancy between IgM and IgG is not completely clear, as the used broad spectrum columns (Ig omni 5) should similarly eliminate IgM and IgG.AppendixS1: Supporting informationClick here for additional data file.


Thousands of youth suffering from acquired brain injury or other early-life neurological disease live, mature, and learn with only limited communication and interaction with their world. Such cognitively capable children are ideal candidates for brain-computer interfaces (BCI). While BCI systems are rapidly evolving, a fundamental gap exists between technological innovators and the patients and families who stand to benefit. Forays into translating BCI systems to children in recent years have revealed that kids can learn to operate simple BCI with proficiency akin to adults. BCI could bring significant boons to the lives of many children with severe physical impairment, supporting their complex physical and social needs. However, children have been neglected in BCI research and a collaborative BCI research community is required to unite and push pediatric BCI development forward. To this end, the pediatric BCI Canada collaborative network (BCI-CAN) was formed, under a unified goal to cooperatively drive forward pediatric BCI innovation and impact. This article reflects on the topics and discussions raised in the foundational BCI-CAN meeting held in Toronto, ON, Canada in November 2019 and suggests the next steps required to see BCI impact the lives of children with severe neurological disease and their families. Pediatric brain-computer interface (BCI) is a rapidly developing subfield of BCI research, with its unique challenges, barriers, and advantages  at Gross Motor Function Classification System (GMFCS) level 5; severe neuromuscular conditions such as congenital myopathies; childhood stroke; demyelinating leukodystrophies]. We have seen over the last decade an increasing number and diversity of children and youth for whom the search for a single motoric pathway of control is intractably elusive. The BCI program arose to fill this gap and complements on-going efforts to devise novel somatic controls .The BCI program at Holland Bloorview is motivated by the unmet, pining need for communication and environmental interaction among many children and youth who present without expressive communication Our BCI research deploys three modalities of brain interrogation, near-infrared spectroscopy (NIRS), transcranial Doppler ultrasound (tCD), and electroencephalography (EEG). The majority of our early work focused on the hemodynamic modalities (NIRS and tCD), where we demonstrated viable brain-based control using a variety of different communication interfaces with a broad range of mental tasks and self-regulation approaches, with both young adults and children. With improvements in EEG instrumentation, we have been investing more energy into EEG BCIs and NIRS-EEG hybrids. In addition to the usual evoked potential; e.g., P300 oddball response, Steady-State Visual Evoked Potentials (SSVEPs), or Auditory Steady-State Responses and motor imagery-based BCIs, one of our most promising developments include an auditory-tactile BCI that can allow children with visual impairments to use a BCI. With concomitant motor impairments, these children currently have very few options for communication . Some of our current efforts include the development of more intuitive communication interfaces , mental speech BCIs, and training protocols that accelerate the acquisition of BCI control.Our research program is closely integrated with our BCI clinic, which was founded in 2019. Our BCI clinic team comprises clinical expertise in assistive technology, Therapeutic Recreation (TR), and biomedical engineering. The program is driven to make BCIs accessible to children with disabilities, a population often excluded from BCI research. Children with restricted control over movements and who face challenges finding a reliable assistive device for communication and environmental control are targeted to participate in this program. The main goal of the program is to provide access to BCI for recreation. Toys and games are ideal first activities when learning how to use BCI as it provides a motivating and engaging activity to master a mental task.Our BCI clinic is divided into two streams: training and recreation. The training stream is where our participants first begin with BCI. They learn what BCI is, practice performing mental tasks, and explore a wide variety of toys and video games. Once the child demonstrates consistent control of the BCI over multiple sessions, they enter the recreation stream. The recreation stream allows the child to have continued access to BCI activities and provides the opportunity for experienced BCI users to engage in group BCI activities such as playing multi-player video games.The two BCI clinic streams are extremely interconnected with each other as well as with the research program. Advancements in signal processing and machine learning elucidated in research are applied to the BCI clinic. Practical experience in the BCI clinic informs the development of research projects. Children move freely between the recreation stream and training stream as needed and engage in research projects aimed to improve their BCI performance.A clinical pediatric BCI program was founded at the Alberta Children’s Hospital (ACH) in 2017. The mission was to provide children with severe neurological disabilities and their families the opportunity to access and inform the development of practical BCI systems that could enhance their independence and quality of life.The roots of the program lay in existing, complementary clinical research programs, specifically successful neurotechnology applications in CP populations including non-invasive neuromodulation clinical trials. This familiarity with clinical populations and applied neurotechnology combined with the existing highly skilled personnel including experts in neurology, rehabilitation, neuroscience, and biomedical engineering led to establishing a foundational pediatric BCI program.In 3 years, the program has achieved multiple early aims. A recruitment program was developed that has connected 10–12 individuals and their families with the team and program, each with unique needs and goals. These participants encompass a broad range of clinical diagnosis but share an underlying phenotype of severe physical impairment , minimal hand function (MACS level 5), either non-verbal or significant communication impairment, and evidence of at least a grade 1 cognitive capacity as assessed by parents, caregivers and clinicians. Initial recruitment has largely included participants with quadriplegic CP resulting from a variety of causes  with other children and families fitting the general inclusion criteria also recruited. Multiple BCI technologies have been acquired and tested, ranging from simple EEG-based headsets to advanced control, communication, and rehabilitation systems.Informed by the patients and families themselves, a growing number of applications have been developed, ranging from video games and recreational activities to communication systems, computer control, and art programs.With a patient-centered focus, the program is ready to integrate with leading partners from industry, biomedical engineering, rehabilitation, and broader clinical centers to better realize the potential of BCI to improve the lives of children with a severe disability.A clinical pediatric BCI program was founded at the Glenrose Rehabilitation Hospital (GRH) as part of the I CAN Centre for Assistive Technology in spring 2019. The mission, aligned with provincial partners at the ACH Pediatric BCI Program, is to provide an opportunity for individuals with a severe neurological disability to access and inform the development of non-invasive BCI technologies to achieve greater independence and quality of life. The initial aim is to provide access to BCI as a “just try it” opportunity for children, as well as the exploration of BCI as an alternative technology access method to help meet goals around the use of technology for play/leisure, environmental control, communication, and mobility.The BCI program at the Glenrose has at its core an existing foundation in cutting edge rehabilitation and assistive technologies, prioritizing patient and family engagement in all stages of development. The Glenrose I CAN Centre and Glenrose Rehabilitation Research Innovation and Technology (GRRIT) program has a long history of successful clinical integration of technology tools, as well as highly skilled experts in rehabilitation, assistive technology, engineering, and robotics.Patient-centered translational research is a core element of the GRH BCI program vision, building on Glenrose’s strength of existing multidisciplinary academic partnerships from the Faculties of Rehabilitation Medicine, Engineering, and Medicine and Dentistry at the University of Alberta.Our program’s initial phases have been focused on the acquisition and integration of BCI technologies, obtaining pilot funding, and establishing collaborative relationships with our provincial partners in Calgary (ACH), and participating in the establishment of the BCI-CAN national network. Our initial clinical focus has been to work with children and their parents to build skills, inform quality improvement, and to develop a BCI activity library that includes tasks that are engaging, motivating, and fun. The GRH team has been actively working to recruit and support a variety of clinical populations who could benefit from BCI ranging from children with quadriplegic CP (GMFCS levels 4 and 5) and childhood stroke to Rett Syndrome, posterior fossa syndrome, and traumatic brain injury.The future of BCI technology is promising. Pediatric BCI technology in particular is seeing a surge of interest, with possible improvements in therapeutic outcomes already reported for various patient populations. Early research has suggested that through the assistance of a BCI, neurofeedback based rehabilitation in children with CP may help encourage early neuro-plastic changes which could improve the acquisition of motor control, which would otherwise be more challenging  and physical play . By tapping into the non-muscular nature of BCI, such systems may be able to provide previously excluded populations the opportunity to explore and learn through play. Previous research has demonstrated such mediums as important avenues that encourage continued learning and rehabilitation in children with disabilities  for children with specific characteristics. To begin with, a relatively simple inclusion criterion was sought of a school-aged child with severe neuromotor impairment , impaired communication , and high suspicion by family and/or clinicians of at least a grade 1 level cognitive capacity. Potential candidates are then further screened by the lead neurologist regarding underlying diagnosis, results of neuroimaging and electroencephalographic testing, and other variables that might affect their candidacy. As spaces become available, the top candidates are then invited to the neurology clinic for an assessment where a general introduction to BCI and the program is carefully explained before enrollment is offered.The intake process uses concepts from The Canadian Model of Occupational Performance and Engagement  and as homework. For example, both the child and parent are integral in helping direct the child’s “personalized” visual imagery task to be used in the introductory BCI session. In this example, the homework aspect would require the child and parent to explore, and consequently practice, one of the agreed-upon imagery paradigms  at home. This practice may take the form of repeatedly imagining the designated action without a typical research-grade BCI system providing feedback. Anecdotally, such homework encourages the consistent practice of designated motor imagery and aims to improve familiarity with the BCI-control requirements. Ongoing efforts are underway to provide commercial-grade systems to families to facilitate such potential homework activities. It is important to note that such at-home systems are considered as supplemental tools to facilitate engagement with BCI for the pediatric population, not necessarily to replace existing at-home assistive technology solutions. The many challenges of transitioning BCI systems to the home that have been shown in adult populations may also require special consideration for children.As successful visual imagery can be different for everyone, working with the families and children to choose an effective scheme is of high priority. Input from participants is also used to determine their preference, enjoyment, and views on trialed activities as well as the level of difficulty perceived and other challenges during a session. Feedback is incorporated and discussed with the families and children to determine if they would like to perform such activities again, reset their goals, or try something new.The importance of a patient-first practice cannot be understated. The children who have participated in the above program have reported strong feelings of self-identification and a sense that they are a part of the “research team” for developing pediatric BCI technology. These responses magnify their level of engagement in the program. How all of the above elements are accurately measured and tracked over time to evaluate outcomes and quality improvement are currently being studied.As an emerging field, we must first establish how well typically developing children can operate BCI systems. A primary goal of the network is to evaluate baseline levels of performance across leading EEG-BCI systems and paradigms that are well-established in adults. Baseline measures to consider include classification accuracy of established systems, as well as scores for the agreement between the requested task and the performed task by the children, often measured by Cohen’s kappa. The evaluation of user experience is also essential including measures of tolerability and motivation—factors that are likely to affect performance. Studies are required to determine how to best improve the measurement of these factors, thereby advancing pediatric BCI performance and contributing to the advancement of our clinical pediatric BCI program for children with disabilities.Outcome measures from a clinical BCI program should be first and foremost patient- and family-oriented. Our vision is to bridge the gap between emerging BCI technologies and the patients and families who stand to benefit from their use by creating an environment that engages patients and families to inform and drive technological progress. Primary outcomes in this environment are defined as subjectively meaningful goal achievement which may include improvement in functional abilities, independence, or otherwise enhanced quality of life for the child and/or family. Measurements from these outcomes rely on continuous active engagement from both patients and families in which they can relay their needs, goals, perceived successes, and failures, etc., from the program. Validated approaches in other forms of childhood neurorehabilitation include tools such as the Canadian Occupational Performance Measure (COPM) and goal attainment scaling  would need to be common across sites and which BCI technology might be more flexible. Participants agreed it was imperative to match the quality of signal acquisition for BCI across sites, but not necessarily exact amplifiers or BCI brand names. For example, if each site has a medical-grade EEG system, but these were produced by different manufacturers, the quality should remain comparable enough for multi-site data collection. Consistent data quality would allow the network to share BCI algorithms and progress their development and evaluation. Legal agreements would need to be put in place before sharing such codes and data but were not considered a significant barrier. The development of a representative coalition was proposed to institute channels for communication and sharing of information across the network.A trainee “pre-conference” meeting was held to generate discussion and gain insights into the key topics important to trainees and early-career researchers interested in pursuing pediatric BCI technology and applications. The trainees developed their thoughts through a series of brainstorming sessions in the form of small-group discussions on designated topics. This environment provided space for these researchers to contribute suggestions for realizing the multi-site collaboration and to express their opinions on key related topics. The most prevalent suggestions are summarized in One important outcome in supporting the next generation of trainees is to promote standardization in scientific practice and BCI implementation across all network members. To promote such scientific unity, senior trainees put together a series of online workshops from early April to June 2020 focused on foundational topics in BCI. These workshops were developed with the primary goal of facilitating trainee learning across the network  or clinical teams . The primary goal for the collective network over the coming years is the establishment of structured BCI programs at each site with clear pathways for support across sites.Another unique potential advantage for our network is the opportunity for exchanges, knowledge translation and recruitment between the sites, and future expansion. Affiliation with the network will be beneficial for research sites by providing interdisciplinary training opportunities, shared resources, and facilitated growth of trainees in various aspects of pediatric BCI research. While the original members in the network have been Canadian-based , we have recently engaged other North American groups, such as the NCAN Centre , and envision growing as an international coalition of pediatric BCI groups across the globe. To join our network, please contact the corresponding author (EKL).via both national and international collaborations.The first BCI-CAN network meeting concluded with a clearer vision of our collective short-term aims: (1) to organize efficient communication schemes that promote continued conversations, collaborations, and relationships across the network; (2) to establish a trainee and research team network that can promote learning experiences, knowledge and data sharing, career development, and the education of all stakeholders; and (3) to collectively pursue opportunities for network growth Since this foundational meeting, we have had consistent, positive engagement from across the network. We have hosted over a dozen meetings between the sites, organized multiple learning opportunities on topics ranging from an introduction to core concepts in pediatric BCI to introductory programming basics in MATLAB and Python. We have initiated a multi-site study across our network to evaluate and develop BCI-driven video games for children with severe neurological disabilities which was presented at the international IEEE Engineering in Medicine and Biology Conference 2020 (Kelly et al., Written informed consent was obtained from individuals in This work represents a collective contribution and summary from all authors on this manuscript. EKL collated the accounts and descriptions together, with supervision from AK. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Meeting children's vitamin A (VA) needs remains a policy priority. Doing so efficiently is a fiscal imperative and protecting at‐risk children during policy transitions is a moral imperative. Using the Micronutrient Intervention Modeling tool and data for Cameroon, we predict the impacts and costs of alternative VA intervention programs, identify the least‐cost strategy for meeting targets nationally, and compare it to a business‐as‐usual (BAU) strategy over 10 years. BAU programs effectively cover ∼12.8 million (m) child‐years (CY) and cost ∼$30.1 m; ∼US$2.34 per CY effectively covered. Improving the VA‐fortified oil program, implementing a VA‐fortified bouillon cube program, and periodic VA supplements (VAS) in the North macroregion for 3 years effectively cover ∼13.1 m CY at a cost of ∼US$9.5 m, or ∼US$0.71 per CY effectively covered. The tool then identifies a sequence of subnational policy choices leading from the BAU toward the more efficient strategy, while addressing VA‐attributable mortality concerns. By year 4, fortification programs are predicted to eliminate inadequate VA intake in the South and Cities macroregions, but not the North, where VAS should continue until additional delivery platforms are implemented. This modeling approach offers a concrete example of the strategic use of data to follow the Global Alliance for VA framework and do so efficiently. The objectives of this paper are to apply the Micronutrient Intervention Modeling tool to: update the model with a revised set of vitamin A (VA) intervention programs and data to support them, and identify concrete subnational policy pathways (sequences of VA program modifications) in Cameroon, which are guided by the Global Alliance for Vitamin A framework. Vitamin A deficiency (VAD) affects hundreds of thousands of children globally, particularly in low‐ and middle‐income countries (LMIC),In countries where VA programs, such as food fortification, have been implemented, the Global Alliance for Vitamin A (GAVA) proposed a framework for deciding when to scale back VAS distribution;The Micronutrient Intervention Modeling project (MINIMOD) aims to fill this gap by applying a tool composed of three models  to design and manage micronutrient (MN) intervention programs more efficiently. By predicting the costs and likely health and nutrition impacts of selected existing and new programs, the tool provides information that can be introduced into policy discussions to improve the cost‐effectiveness of national and subnational MN strategies. Previously, the MINIMOD tool was applied to the case of VA programs in Cameroon (where baseline VAD rates among young children ranged from over 40% inflammation‐adjusted retinol‐binding protein <0.83 µmol/L in the North macroregion to less than 25% in the South macroregion), to identify the most cost‐effective mix of programs that would achieve the same effective coverage as current  programs , and fortified edible oil).the most cost‐effective strategy for meeting VA nutrition objectives nationally; and then (3) identify macroregional, year‐by‐year policy pathways (programmatic changes) leading from a BAU scenario toward more efficient sets of policies that achieve adequate VA intake while protecting children from VAD‐related mortality during policy transitions.The objectives of this paper are to apply the MINIMOD tool to update the model with a revised set of VA intervention programs and data to support them, and to identify concrete subnational policy pathways (sequences of VA program modifications) in Cameroon, which are guided by the GAVA framework.macroregion–specific policy pathways that lead from the BAU strategy to a more efficient set of VA programs, but constrained to adhere to the original GAVA framework. Finally, we calculated the costs associated with adhering to the GAVA protocol.Previously, we used the MINIMOD tool's nutrition benefits model to predict the effects of alternative VA intervention programs, and combinations thereof, on dietary VA adequacyA broad array of programs and policies exist that have the potential to directly  or indirectly  increase VA intake. Decision makers in Cameroon were most interested in a subset of programs that were underway or were being discussed as possible additional/replacement interventions. More specifically, a fortification program for edible oils (consumed on the previous day by 39% (South macroregion) to 79% any additional VA because of a given program, regardless of how much additional VA was consumed, or whether an individual had low VA intake or status. Effective coverage was defined as the proportion of individuals who had inadequate dietary VA intake and subsequently achieved adequate intake as a result of one or more VA intervention programs. Effective coverage was calculated by estimating the prevalence of dietary VA adequacy at baseline  and under different programmatic scenarios  to calculate the increase in proportion of individuals with adequate VA intake. The Lives Saved Tool (LiST) modelThe target population for VA intervention programs in Cameroon is children 6–59 months of age. We calculated three indicators of program impact .We simulated the effects of VA intervention programs, and combinations of them, by calculating the additional daily VA intake contributed by one or more programs and adding this to each person's baseline intake. The specific method applied for each type of intervention program is described below. We then reapplied the NCI method to estimate the postintervention distribution of usual intakes and prevalence of inadequate intake under each scenario.To estimate the contribution of fortified edible oil to dietary VA intake, we multiplied fortifiable oil consumption (grams per day) by the assumed fortification level. Two scenarios were modeled: (1) implementation of VA fortification at 44% of the target level of 12 mg/kg of oil, based on measurements of fortified oil samples from a program evaluation;To estimate the contribution of biofortified maize, we assumed that the consumed product contains 0.34 µg of beta‐carotene RAE per kcal,To estimate the contribution of high‐dose VA supplements to dietary VA adequacy, a daily intake equivalent of 167 µg retinol activity equivalents per day (RAE/day) was developed;We estimated the number of child deaths averted through VA intervention programs by introducing effective coverage estimates into Lives Saved Tool (LiST)To estimate the costsCosts of large‐scale fortification programs were drawn primarily from budgets created by Helen Keller International‐Cameroon. Program costs included program planning costs, up‐front investments required to outfit edible oil filtering/containerizing production processes to blend in fortificants, the costs of fortificants, and the private and public costs associated with program monitoring and evaluation. The costs associated with designing and implementing a fortified bouillon cube program, including a 3‐year start‐up period during which costs would be incurred but no nutritional benefits would be generated, were based on input provided at a 2014 cost workshop by members of the food industry and organizations that designed and managed the national edible oil and wheat flour fortification programs.In some of the results that follow, we examined the potential effects of improving the efficiency and effectiveness of current large‐scale fortification programs, by increasing investments in the monitoring and evaluation of programs to ensure full industry compliance.Biofortification refers to the process of selectively breeding varieties of staple crops so that they contain higher‐than‐average, bioavailable amounts of key MNs.CHDs in Cameroon target all children 6–59 months of age, regardless of their health or nutritional status.,An array of products and services are generally provided during CHDs, for example, the distribution of high‐dose VAS and DW tablets, catch‐up immunizations, and sometimes oral polio vaccine. For the purposes of this paper, we focused only on VAS. To isolate the costs of these interventions, we first removed costs directly related to vaccinations, for example, vaccination teams, vaccination training, vaccine costs, and so on. We then assumed that 90% of the overhead costs associated with CHDs would have to be covered by the VAS program.national BAU programs’ outcomes, namely CY effectively covered and lives saved over the entire 10‐year planning time horizon. The BAU programs were composed of a national VA‐fortified edible oil program that nationally delivers approximately 44% of the targeted amount of VA and a national VAS program delivered via CHD.We used the MINIMOD economic optimization model to identify the most cost‐effective strategy for addressing inadequate VA intake among young children.most cost‐effective combinations of VA intervention programs nationally over 10 years for meeting a prespecified target, in this case, the number of CY effectively covered by the BAU programs. However, transitioning from the BAU set of programs to the economically optimal set of programs will not be immediate or free of additional costs; a variety of technical, political, and other issues will also need to be addressed, and investments may be required to upgrade existing programs and to put new programs in place. Depending on the issues to be addressed and the program upgrades to be made, progress can be quicker or slower, and progress can vary by macroregion. Moreover, achieving the nationally economically optimal solution will generally involve trade‐offs across macroregions regarding where cases of VAD are resolved; by design, the model takes advantage of macroregional differences in VAD and region‐specific differences in the cost‐effectiveness of alternative VA intervention programs in addressing VAD. It is possible that some trade‐offs suggested by the model may be deemed unacceptable for political or other reasons, and objectives may be established for macroregions rather than for the entire nation.The MINIMOD economic optimization model will identify the policy pathways  that address these issues, and thereby generate political support for medium‐term strategies for reducing MN deficiencies, and help secure financial support for these transitions. The MINIMOD tool allows for the examination of multiple pathways leading from the BAU strategy toward the economically optimal set of VA intervention programs for each macroregion, on an annual time‐step. In what follows, we use the MINIMOD tool to examine one such pathway for each of Cameroon's macroregions separately,Therefore, it is important to identify There are two (summary) sources of uncertainty in the MINIMOD tool: the estimated nutritional benefits and the estimated costs of alternative VA intervention programs. To assess the extent to which these sources of uncertainty affect the programs chosen by the economic optimization model, probability distributions around the point estimates of benefits and costs were constructed, and Monte Carlo simulations involving 1000 simulations based on random draws from those distributions were performed. Probability distributions were constructed using standard errors for effective coverage estimates ; for costs, uniform distributions of costs ±20% were constructed to generate 95% intervals.For each of the VA intervention programs considered, the projected 10‐yearIn terms of program reach, the VA‐fortified bouillon cube program was predicted to reach the largest number of children (>29 m children over 10 years).The number of children reached by all interventions was much larger than the number effectively covered, which in turn was much larger than the number of child deaths averted. The ranking of program impact changed as the measure of success moved from reach to effective coverage, reflecting differences in the amounts of VA delivered to children by each program. The ranking remained unchanged, however, if child deaths averted was chosen as the impact measure instead of effective coverage. The most effective VA intervention program over 10 years in terms of effective coverage (∼8.6 m CY) and lives saved  was VAS delivered via CHD. A close second was the enhanced VA‐fortified oil program, which over 10 years would effectively cover ∼8 m CY and save 15,527 lives. At the other end of the effectiveness spectrum, the biofortified maize program was estimated to effectively cover ∼2.5 m children and to save 5720 lives. The unenhanced VA‐fortified oil program and the VA‐fortified bouillon program effectively covered ∼5 and ∼7.7 m CY, respectively, and saved 9724 and 16,068 lives, respectively.There was subnational variation for all measures of program impact, especially for reach, due primarily to variations in diets and in the consumption of fortifiable products across macroregions. Cross‐macroregional differences in effective coverage and deaths averted were also evident for all VA intervention programs, but were most notable for VAS, biofortified maize, and bouillon cubes; these differences were primarily attributable to lower VA intake in the North macroregion, and to maize consumption patterns (more common in the North macroregion).VA intervention program costs varied substantially across the candidate programs examined in Table As was the case for program effects, program costs and cost‐effectiveness also varied across macroregions. For example, cost per child death averted for the VAS program varied from $3333 in the South to $643 in the North.Cameroon already invests in two national programs to meet children's VA needs: a national VA‐fortified edible oil programOver a 10‐year period, the pair of VA intervention programs effectively covers approximately 12.8 m CY and costs approximately US$30 m, for an average cost of approximately US$2.34 per child‐year effectively covered  confirm the potential for VA intervention program efficiency gains. The enhanced fortified cooking oil program and the VA‐fortified bouillon cube program are selected by the model, even though the former does not reach peak performance until the fourth year of the simulation time horizon (Y4), and the latter faces costs but generates no benefits until Y4. Note also that the biofortified maize program is not selected. Although it is a relatively inexpensive program that reaches many millions of children, this intervention is predicted to effectively cover few children in this age range  are selected in only a small fraction of those simulation results, and the VA‐biofortified maize appears in slightly over 11% of these simulation results.The simulated values and their 95% intervals (in parentheses) appear in Table national economically optimal strategy for implementing cost‐effective MN intervention programs. Yet, transitioning from the BAU to this lowest‐cost collection of VA intervention programs will require investments and time, and national, regional governments, and partners may have strong preferences regarding managing VAD at different spatial scales and over different time horizons. The MINIMOD tool allows policymakers to identify macroregion‐specific policy pathways and to specify alternative objectives. We present the results for three macroregions (separately), below, and also shift the focus from achieving national BAU effective coverage results to eliminating VAD in each macroregion.The MINIMOD tool identifies the In the policy pathways analysis, the VAS program is maintained in the South until Y6 Fig. A, as parAt the beginning of the simulation period, 19% of children have inadequate intake . Figure We share the global commitment to achieving sustainable, food‐based solutions to MN deficiency problems, and to identifying the policies, technologies, and institutional arrangements that will create and support them. However, in the short and medium terms, dietary intakes in the absence of large‐scale food fortification are likely to fall short of providing the amounts and types of MN required—this is especially true among children as well as women of reproductive age (WRA) in resource‐poor households in developing countries. For these populations, the fortification of staple foods can contribute significantly to achieving dietary adequacy, but in some settings, even combinations of food fortification programs will not meet needs. In such cases, direct supplementation will be required.High‐dose VAS has been distributed through twice‐annual campaigns in LMIC for decades as a strategy to reduce child mortality. When VAS stakeholders are asked to cover the operational costs of the campaign (versus just covering the costs of providing capsules), as may become more likely as vaccination campaigns are phased out, this platform becomes quite expensive and thus unsustainable.We used the MINIMOD tool and data for Cameroon to estimate the costs and likely nutritional impacts of various VA intervention programs—some of which have the potential to be implemented subnationally—on VA dietary adequacy and VA‐attributable deaths averted among young children.individual VA intervention programs. First, as we have shown in earlier work,reach as a program objective will yield a very different selection of VA intervention programs than would be the case if lives saved were chosen as a program objective. Second, there is considerable variation in the costs associated with VA intervention programs. Third, the effects, costs, and (hence) cost‐effectiveness of all programs vary subnationally. These differences in cost‐effectiveness, across programs, across macroregions, and over time, suggest that efficiency gains might be achievable by shifting resources from less cost‐effective programs and macroregions to more cost‐effective programs and macroregions.Several important points emerge from the examination of the effects and costs of We also modeled combinations of investments in addressing VAD, for example, investing approximately $2.2 m over 3 years to improve the effectiveness of the VA oil fortification program from its baseline of 44% of targeted amount of fortification to 75% (Y2), to 100% (Y3–Y10), and investing $2.9 m in the establishment, promotion, and launching and M&E of VA‐fortified bouillon cubes, which would become available via retail outlets and (hence) begin to generate nutritional benefits in Y4. The strategy modeled also retains VAS for at‐risk children until the prevalence of inadequate VA intake falls below 2.5%, at which point inadequate VA intake would be expected to have decreased to thresholds suggesting that VAD is no longer a public health problem. The 2.5% threshold for inadequate intake was based on general targets for food fortification programs because there are no formal guidelines for the prevalence of inadequate intake that indicates a public health problem (or lack thereof), or that corresponds to a given prevalence of  VAD. As estimates of dietary intake become less stable at the tails of the distribution , a slightly higher threshold may also be appropriate. Specific guidance is needed on decision‐making thresholds for each type of data, as more countries seek to use dietary data to guide such programmatic decisions.not selected—costs are relatively low, but nutritional benefits for young children are low, too.As expected, the pathways from BAU toward the more cost‐effective combinations of VA intervention programs varied by macroregion. There are some commonalities, though. First, the model selects the national enhanced VA‐fortified edible oils  despite its higher cost. Second, a national program to fortify bouillon cubes is chosen, despite its 3‐year start‐up period during which costs are faced but no nutritional benefits are delivered. Third, the national VA‐biofortified maize program is These analyses provide concrete and practical guidance for Cameroon regarding the cost‐effective management of VAD, nationally and subnationally. They can also serve as a model for other countries to develop evidence‐based options for transitioning from short‐ to medium‐term VAD management strategies.Importantly, these modeling results assume that intervention programs, including the M&E activities associated with them, are all operating at the levels modeled. This does not mean that we assume that programs reach 100% of the population (reach estimates are based on survey data), but we do assume that program performance is constant over time, or that it follows the performance trend included in the model. Inadequate program implementation would reduce the predicted impact on VA intake. Program implementation should be continuously monitored, and these data used to guide efforts to improve program performance. In addition, the validation studies recommended by the GAVA framework are critical to confirm that population VA status is adequate before withdrawing VAS programs. The updated GAVA framework does not specify the need for repeated validation studies before withdrawing VAS (as long as sufficient data are available to confirm adequate dietary VA intake); compared with the two‐validation framework, this approach saves field research costs and extends the timeframe for accruing programmatic savings associated with ending VAS. Finally, any programmatic changes should be accompanied by activities to monitor population status, including child mortality rates in the case of countries or regions considering withdrawing VAS programs.The research underlying this paper has several limitations. First, the start‐up and ongoing costs of M&E activities associated with all VA intervention programs are included in all model simulations, and it is assumed that these M&E activities are in place and operating as intended. This is a perennial challenge in the context of developing countries, and third‐party confirmation may be required.Second, the results presented are taken from a case study of Cameroon, an agroecologically and culturally diverse country, and consequently with a broad array of dietary intake patterns and geographic variation in MN deficiencies. Other sites may be less diverse, and their resident populations may therefore have more similar diets and prevalence rates of MN deficiencies. However, even within homogeneous agroecologies, dietary differences may exist among different socioeconomic groups, and in rural versus urban settings. Therefore, throughout other LMIC, one should expect to find dietary differences and consequently differences in the prevalence rates and severities of inadequate MN dietary intake. Regardless of the reasons for such variability, the approach adopted, and the analyses undertaken here, will generally be useful.Third, other MN deficiencies  can matter greatly for children and other beneficiary groups in Cameroon, and some of the products that could be included in this analysis  can address these deficiencies. The benefits that these products might contribute to addressing MN deficiencies other than VA are not included in this analysis—doing so would increase the chances of, but would not guarantee, their being included in the economically optimal set of MN intervention programs.Fourth, some MN intervention programs convey other products or information that may be useful in addressing VAD. For example, in addition to VAS, CHD often provide DW tablets and guidance to mothers regarding breastfeeding, both of which can affect the VA status of children. Neither the benefits (in terms of estimated improvements in VA status) or the costs of these elements of CHD programs are included in this analysis, although previous analyses suggest that the contribution of DW tablets to improved VA status is small.Fifth, this paper focuses exclusively on young children, on VAD among them, and on the impacts, costs, and cost‐effectiveness of alternative combinations of VA intervention programs to address VAD. There are other groups in society who suffer from the consequences of VAD, for example, WRA, who would not benefit from some of the interventions addressed in this analysis  but would benefit from other programs . The cobenefits to WRA of fortification programs are not included in the analyses presented here, but if they were, they would strengthen the case for their inclusion in the cost‐effective strategy. However, VA‐biofortified maize, which the model does not select because it delivers very little dietary VA to children, may well be selected as a cost‐effective program if the focus were to shift to include WRA. These and other cobenefits are worthy of further study.Sixth, the estimated effects of the benefits of MN intervention programs are based on detailed dietary intake data that are now somewhat dated , and these data do not account for seasonal variations in dietary intake. Changes in food consumption habits and breastfeeding patterns could alter baseline MN intake in ways that might affect the marginal impacts of MN intervention programs, but we do not believe that the core policy messages included in this paper would be affected.Seventh, as with any modeling effort, it was necessary to make certain assumptions to fully populate the tool. For example, we present single estimates of lives saved  rather than ranges attributable to, for example, uncertainty regarding cause‐specific mortality rates at subnational level. However, model robustness tests strongly suggest that even when uncertainty regarding benefits and costs is introduced into the MINIMOD tool, the policy messages included in this paper are not affected.Eight, we did not explore the impacts, costs, or cost‐effectiveness of alternative distribution models or platforms for VAS. This will be the focus of future work.Finally, the costs associated with MN intervention programs included in the tool are somewhat dated (2013–2014) and these costs are held constant over the simulation timeframe, with the exception of costs that vary with the size of the target population (preschool children). In reality, these costs may vary over time, perhaps especially for CHD programs. However, sensitivity analyses suggest that core policy messages are robust to uncertainty related to costs and nutritional benefits.Appropriate and timely data collection, analysis, and interpretation efforts are needed to document and understand the prevalence and severity of VAD, and the spatial patterns of deficiency. National and subnational perspectives and policies are needed to establish and manage cost‐effective strategies for addressing VAD.The GAVA framework provides guidance for countries with ongoing VA fortification programs that are considering withdrawing VAS. However, for countries at an earlier stage, efforts should focus on putting in place cost‐effective strategies to address VAD. Methods and tools, such as those developed through the MINIMOD project, are needed to develop, prioritize, and strengthen national and subnational programs over time to address underlying VA intake and status.not predicted to reduce inadequate VA intake among children sufficiently to allow for the cessation of VAS programs.In these simulations for Cameroon, the current edible oil fortification program is predicted to contribute to meeting VA needs of young children; improving program management can increase its effectiveness and cost‐effectiveness. Initiating a VA‐fortified bouillon cube program could also make cost‐effective contributions to addressing VAD. In the South and Cities macroregions, these programs, once mature, are predicted to reduce inadequate VA intake among children to less than 2.5%, suggesting that dietary VA intake is adequate for that population. Once these predictions are validated in accordance with the GAVA framework, VAS programs can be curtailed, since their contributions to reducing VA‐attributable child mortality will be very small. In the North macroregion, the mature food fortification programs included in this analysis are Several important policy messages emerge. First, continuing the BAU is the costliest of the strategies explored here—all of which achieve essentially the same number of effectively covered CY and avert essentially the same number of VA‐preventable child deaths. Thus, it is worthwhile to plan the process to transition to cheaper and more sustainable strategies to address VAD.Second, investments in and better management of VA intervention programs can significantly reduce the cost of meeting children's VA needs. For example, enhancing the performance of the VA‐fortified oil program, investing in a VA‐fortified bouillon cube program, and focusing VAS activities in the North macroregion would save over $5 m .Third, the choice of one versus two validation studies has large fiscal consequences; for example, 2 years of additional VAS plus a second validation study in the south macroregion costs approximately US$2.9 m, but is still less expensive than continuing BAU indefinitely.Fourth, the results presented here envision 3‐year periods for upgrading the VA‐fortified oil program, and for designing and implementing the VA‐fortified bouillon cube program. There are substantial savings associated with speeding up these processes and substantial reductions in savings associated with delays. Gains from effective M&E programs are also large. Hence, policymakers have very substantial fiscal incentives to design and implement new programs quickly, and to manage new and existing programs well.necessary to identify the expected benefits and costs of alternative strategies for addressing MN deficiencies, and hence to formulate sound MN intervention policies. A recent report highlighted the lack of recent data on VAD prevalence among countries with VAS distribution programs.Finally, and very importantly, detailed nationally representative data on dietary intake and biomarkers, and on MN intervention program costs, are S.A.V., J.K., R.E.S., and K.H.B. designed the study; S.A.V., J.K., R.E.S., and K.H.B. developed methods; J.K., R.E.S., and H.L. analyzed the data and performed model simulations; and S.A.V., J.K., and R.E.S. wrote the first draft of the paper. All authors contributed to data interpretation and revisions of the paper and approved the final version.The authors declare no competing interests.


Immediately after a destructive earthquake, the real-time seismological community has a major focus on rapidly estimating the felt area and the extent of ground shaking. This estimate provides critical guidance for government emergency response teams to conduct orderly rescue and recovery operations in the damaged areas. While considerable efforts have been made in this direction, it still remains a realistic challenge for gathering macro-seismic data in a timely, accurate and cost-effective manner. To this end, we introduce a new direction to improve the information acquisition through monitoring the real-time information-seeking behaviors in the search engine queries, which are submitted by tens of millions of users after earthquakes. Specifically, we provide a very efficient, robust and machine-learning-assisted method for mapping the user-reported ground shaking distribution through the large-scale analysis of real-time search queries from a dominant search engine in China. In our approach, each query is regarded as a “crowd sensor” with a certain weight of confidence to proactively report the shaking location and extent. By fitting the epicenters of earthquakes occurred in mainland China from 2014 to 2018 with well-designed machine learning models, we can efficiently learn the realistic weight of confidence for each search query and sketch the felt areas and intensity distributions for most of the earthquakes. Indeed, this approach paves the way for using real-time search engine queries to efficiently map earthquake felt area in the regions with a relatively large population of search engine users. As a result, the significance of real-time seismology has been substantially recognized, and considerable progress has been made in this area during the past decades4. Along this line, a major research focus of real-time seismological community is to efficiently estimate the felt area and extent of ground shaking, immediately after a significant earthquake occurs, which provides critical guidance for government emergency response teams to conduct orderly rescue and recovery operations in the damaged areas.Earthquake is a major natural geological disaster, inflicting huge economic losses and casualties worldwide every year. Although the precise short-term earthquake predictions are still difficult to achieve, the impact of significant earthquakes can be largely mitigated through the rapid estimation of post-disaster information and quick response decisions7, and be used to automatically estimate the earthquake felt area and intensity distributions through their quantitative relationship10, such as the implementation of ShakeMap system11 and GRSmap12. However, the construction of a dense seismic observation network for earthquake early warning is not trivial, which is always accompanied with huge financial cost and unavoidable difficulties due to the constraints of field environment or local policies. Therefore, for most regions with limited observation stations, as the current situation in China, the earthquake felt area is mainly mapped based on the result of field investigation by seismologists, and assisted with inference methods like empirical attenuation relationship models14. However, this kind of approach often costs a couple of hours to days, sometimes even months, with heavy labor burden, and cannot cover a wide range of regions. For example, as reported by China Earthquake Administration (CEA) officially, it costed about four days for drawing the intensity map of 15.Traditionally, in a few regions with densely-deployed seismic observation stations, the ground motion parameters can be accurately detected18 and GPS trajectories from mobile devices20. With the development of the Internet, it becomes possible to collect user-reported macro-seismic data in a more convenient manner. The online feedbacks can be regarded as a kind of “crowd sensors” and intuitively tend to correlate with the disaster distribution. For example, the “Did You Feel It?” (DYFI) system21 developed by United States Geological Survey (USGS) and the LastQuake app22 developed by European-Mediterranean Seismological Centre (EMSC) have been collecting information from people who felt earthquakes and creating maps that show what people experienced and the extent of expected damage. Moreover, tweets also have been shown as an effective way to reflect people’s feelings of earthquake shaking, which can help to facilitate the construction of earthquake early warning systems28. However, due to the reasons of the limited popularity , the non-real-time mechanism of information sharing , or the noisy information of alternative data, the efficiency, coverage and reliability of these approaches usually cannot be guaranteed.Instead, researchers have made many efforts on finding cost-effective alternatives to estimate the earthquake felt area, such as the estimation based on remote sensing data from geographic information system (GIS)30, which are submitted by tens of millions of users after earthquakes. Usually, when an earthquake occurs, people who felt the shaking will be urgent to know what exactly happened. In most cases, online search engine is the first and most convenient choice to obtain such information, compared with other information sources. Therefore, by monitoring the spatial-temporal distribution of real-time search queries that contain keyword “Earthquake”, we can estimate the felt area distribution in a timely manner. Specifically, we propose a very efficient, robust and machine-learning-assisted approach, namely Query based Felt-area (Q-Felt) Map, to sketch the user-reported ground shaking distribution, through the large-scale analysis of real-time search queries from a dominant search engine in China. In our approach, each query is regarded as a “crowd sensor” with certain weight of confidence to proactively report the shaking location and extent. Figure Q-Felt Map, which consists of three major components, namely Query Screening based on Machine Learning, Direction Detection based on Principle Component Analysis (PCA), and Density based Isoseismal Line Segmentation. We validate our Q-Felt Map based on the large-scale search engine queries and historical earthquakes occurred in mainland China from 2014 to 2018. Experimental results clearly demonstrate that our approach can efficiently and realistically sketch the felt area maps for most of the earthquakes occurred in mainland China, by using real-time search queries after the earthquake. This approach paves the way for using real-time search engine queries to efficiently map earthquake felt area in the regions with a relatively large population of search engine users.To this end, here we introduce a new way for estimating the earthquake felt area and intensity distribution through monitoring the real-time information-seeking behaviors in the search engine queriesIntuitively, if we simply draw the distribution based on the density of search queries, the results will be overwhelmed by the regions that have large population of search engine users, such as the metropolis around. Meanwhile, not all the search queries are relevant to the occurred earthquake due to the diverse search intent. Therefore, it is necessary for us to find a way for screening the queries, i.e., filter out the noisy information contained in the massive query data. Accordingly, we regard each search query has a weight of confidence, which indicates the effectiveness of this query in terms of an earthquake sensor. Generally, the weight will be influenced by a number of factors, such as the submitted time, location, and surrounding population of query. For example, a query submitted right after the earthquake, which is from a location with relatively sparse population, is more properly to be an effective report. To estimate the weights of queries, we propose a machine learning approach, as shown in Fig. Q-Felt Map, we also use isoseismal line as the indicator for sketching the felt areas of people-perceived ground shaking. Along this line, the first task is how to determine the directions of semi-major axis (or semi-minor axis) based on the screened queries. Here, we use the weighted PCA algorithm to project the locations of weighted queries onto new orthogonal coordinate system (see details in Method). After that, the obtained two eigenvectors can be used as the directional vectors, where the direction of eigenvector with larger value is for semi-major axis. Intuitively, the isoseismal line can be generalized by a series of concentric ellipses. Therefore, in the Q-Felt Map, we use the estimated epicenter as the origin of coordinate, and the eigenvalues are used for determining the flattening of ellipse.Traditionally, the isoseismal line is widely adopted for describing the felt area and extent of earthquake shaking. Therefore, in the Q-Felt Map. Intuitively, the isoseismal lines are used to describe various degree of felt intensities. Although the districts segmented by isoseismal lines in the Q-Felt Map cannot be directly mapped into traditional intensity scales, such as the Modified Mercalli Intensity scale, the isoseismal lines can still be regarded as an alternative indicator for indexing the distribution and attenuation of people-perceived shaking intensity. Therefore, our Q-Felt Map provides a brand-new perspective on mapping the intensity distribution of earthquake.Furthermore, we need to determine the value of semi-major axis and semi-minor axis length in isoseismal line, which is used to segment districts with different extent of ground shaking. To this end, here we design a density-based segmentation algorithm to draw the isoseismal (see details in Method). Figure 21. Meanwhile, we find that both training and testing errors become relatively stable and convergent, which indicates that using more queries will not significantly influence the learning results. This indicates that, for most cases, it could be enough for only using queries 5 minutes after the earthquake. After obtaining the optimal coefficients, we can compute the weight for each query.To validate the feasibility of our approach, we collected a dataset that contains the records of earthquakes occurred in mainland China from June 2014 to June 2018, from the China Earthquake Network Center (CENC), and conducted a standard five-fold cross validation on selected 554 earthquakes for training the machine leaning model (see details in Method). Actually, although the model can be constantly revised according to the update of queries, an open question is how many queries should be enough for learning the weights? To this end, we evaluated the performance of our machine learning model by selecting queries within different time intervals after earthquake as experimental data. From the results shown in Fig. Q-Felt Maps for all the 58 earthquakes with magnitude Q-Felt Maps by leveraging search queries only 5 minutes after the earthquake , it still can be regarded as an alternative benchmark for validating the felt maps. Therefore, to further validate the effectiveness, we also compared the Q-Felt Map, which directly affects the number of submitted search queries within the disaster regions. Intuitively, as shown in Fig. Q-Felt Map fails to highlight the exact disaster distribution. However, if the epicenter is near the densely populated areas, the situation will be totally different, such as the Q-Felt Map of Q-Felt Map can still capture the queries and sketch the meizoseismal area.Indeed, the population of online search engine users around the epicenter plays an important role in drawing Q-Felt Maps and official intensity maps of some earthquakes have large overlapped region but different directions of semi-major axis .None of the queries in the database of this project can be associated with a particular individual. The database only retains information about the submission time and GPS coordinates of queries that contains the Chinese keyword “Earthquake”, instead of information about the identity of any user. Furthermore, any of original search logs are being processed and used in accordance with Baidu’s privacy policy (The earthquake records and corresponding intensity maps were provided by the China Earthquake Network Center (CENC). Each record contains the magnitude, the GPS coordinates of the epicenter, and the initial time of an earthquake occurred during June 1st, 2014 to June 1st, 2018. To avoid the noise for learning the weights of queries, we only retained the earthquakes with magnitude no less than The search query records were provided by Baidu Inc. Each record only consists of the submission time and GPS coordinates of queries that contain the Chinese keyword “Earthquake”. In this study, we used the search queries submitted within 5 minutes after the earthquakes to validate the efficiency of our approach, while some experimental results by using search queries within 10 minutes can also be found in the Supplementary Information.In this study, two kinds of data were used, namely the earthquake records and the search engine query records. For each query The representation of query time. We defined a one-hot feature vector ti of query The representation of query location. We defined a one-hot feature vector The representation of population density. We defined a one-hot feature vector The dimension of the feature vector might be different with respect to different length of time interval for learning query weight. In this study, we totally extracted 122 one-hot features for each query submitted within 5 minutes after an earthquake occurred. Specifically, given an earthquake N earthquakes with official coordinates For each query Q-Felt Map is centered on the estimated epicenter Q-Felt Map, respectively. Meanwhile, the flattening of Q-Felt Map is computed as After getting the weight of queries after earthquake The basic idea is to constantly enlarge the boundary of an ellipse from the origin or the boundary of the last ellipse, with the learned flattening, until there exists a sharp change of the weight sum of queries located within this ellipse. The intuition is if the regions have similar extent of devastation, the increase of the weight sum should be stable. As a results, for every sharp change, we can draw a concentric ellipse. Specifically, to draw the isoseismal lines, we first generated a set of concentric ellipses In this paper, due to the data limitation, we did not discuss the correlation between the felt intensity with some recorded ground motion parameters, which is indeed an interesting direction for future research.Supplementary Information 1.Supplementary Information 2.