This paper assesses the effectiveness of community–based primary health care (CBPHC) in improving child health beyond the neonatal period. Although there has been an accelerated decline in global under–5 mortality since 2000, mortality rates remain high in much of sub–Saharan Africa and in some south Asian countries where under–5 mortality is also decreasing more slowly. Essential interventions for child health at the community level have been identified. Our review aims to contribute further to this knowledge by examining how strong the evidence is and exploring in greater detail what specific interventions and implementation strategies appear to be effective.We reviewed relevant documents from 1950 onwards using a detailed protocol. Peer reviewed documents, reports and books assessing the impact of one or more CBPHC interventions on child health  among children in a geographically defined population was examined for inclusion. Two separate reviews took place of each document followed by an independent consolidated summative review. Data from the latter review were transferred to electronic database for analysis.The findings provide strong evidence that the major causes of child mortality in resource–constrained settings can be addressed at the community level largely by engaging communities and supporting community–level workers. For all major categories of interventions  we have presented randomized controlled trials that have consistently produced statistically significant and operationally important effects.This review shows that there is strong evidence of effectiveness for CBPHC implementation of an extensive range of interventions to improve child health and that four major strategies for delivering these interventions are effective. This paper concentrates on the effectiveness of community–based primary health care (CBPHC) in improving the health of children beyond the neonatal period. In 2015, the global mortality rate for children younger than 5 years of age  was 42.5 per 1000 live births, a decline from 90.4 per 1000 live births in 1990 .Essential interventions for child health at the community level have been identified as: promotion of breastfeeding and complementary feeding, supplementation with vitamin A and zinc, immunizations, co–trimoxazole for HIV–positive children, education on the safe disposal of feces and hand washing, distribution and promotion of insecticide–treated bed nets (ITNs) or indoor residual spraying (IRS) or both; detection and treatment or referral of children with severe acute undernutrition; and detection and treatment of pneumonia, malaria and diarrhea without danger signs and referral if danger signs appear . It has Our review aims to contribute further to this knowledge by examining how strong is the evidence for community–based primary health care (CBPHC) and exploring in greater detail what specific activities appear to be effective. Our concern is not just to strengthen the evidence about which interventions work at the community level but who does them and how, what conditions facilitate effectiveness, and what kinds of community–based approaches appear to be most effective. What characteristics do effective CBPHC activities share, and how strong is the evidence that partnerships between communities and health systems are required in order to improve child and maternal health?The purpose of this paper is to summarize the evidence regarding the effectiveness of CBPHC for improving child health beyond the neonatal period.Our review aims to provide a comprehensive review of documents from 1950 onwards assessing the effectiveness of projects, programs and research studies (hereafter referred to as projects) using a detailed protocol. We examined peer–reviewed articles, reports and books assessing the impact of one or more CBPHC interventions on child health , among children in a geographically defined population. Two independent reviews were carried out and followed by an independent consolidated summative review. Data from the latter review were transferred to an electronic database for analysis. Data analysis took place using EPI INFO version 3.5.4 .Only those assessments which had clear documentation of the intervention(s) and their impact on child health where included. Outcome measures included were changes in the population coverage of one or more evidence–based interventions; change in nutritional status ; change in the incidence or in the outcome of serious, life–threatening morbidity ; and change in mortality . Further details regarding the methodology are reported elsewhere in this series . Two other RCTs demonstrated that CHWs can decrease the clinical severity of pneumonia significantly by treating respiratory infections at the community level through implementing good–quality case management . Over 20 other studies showed decreases in child pneumonia–specific incidence or mortality but as their pneumonia case management was part of Integrated Management of Childhood Illnesses (IMCI) or Primary Health Care (PHC), they will be discussed under those sections below. Co–trimoxazole was the antibiotic most commonly used by CHWs in these studies.This part of the framework includes diagnosis, screening, triage and treatment. Our review includes five randomized controlled studies (RCTs) that all showed operationally important and statistically significant reductions in child mortality as a result of community health worker (CHW) treatment of pneumonia with antibiotics – reductions in the range of 13% to 60% [S1–5]. Throughout this article we will be referencing assessments from our database with numbers in brackets, preceded by an S prefix, to distinguish them from the references cited in the list of references at the end of this article. The number in brackets with an S prefix refers to the number of the assessment in Appendix S2 in Under this component are good health practices from birth: exclusive breastfeeding during the first six months of life, adequate complementary feeding, and vitamin A supplementation. Several RCTs demonstrated the efficacy of community–based vitamin A supplementation in reducing pneumonia mortality. In one, vitamin A supplementation decreased pneumonia–specific child mortality by 26% [S14]. In another study, the incidence of pneumonia was decreased through vitamin A supplementation by 44% [S15]. Zinc supplementation and promotion of hand washing provided by CHWs were each also found to significantly decrease the incidence of both pneumonia and diarrhea . In one randomized controlled trial assessment, a community–based integrated nutrition program apparently not including vitamin A or zinc supplementation demonstrated a decreased incidence of pneumonia [S18]. Studies of vitamin A and zinc supplementation will be presented in more detail under the nutrition section below. Further studies have demonstrated the strong efficacy of zinc supplementation in reducing the incidence, severity and/or duration of diarrheal episodes in children [S19–24].This component includes vaccinations, hand washing with soap, safe drinking water and sanitation, reducing household air pollution, HIV prevention and co–trimoxazole prophylaxis for HIV–infected and HIV–exposed children. Education of community members about diarrheal disease was a common activity carried out by trained CHWs, usually by visiting households or meeting with community groups. Randomized controlled trials found that community education focused specifically on the importance of proper disposal of animal feces from living areas produced decreases in the incidence of childhood diarrhea . Randomized controlled trial assessments of education of caregivers about hand washing along with the provision of soap also decreased childhood diarrhea to an even greater degree than those mentioned in the previous sentence [S27–31]. Teaching mothers to use oral rehydration solution at home along with education about good household sanitation practices – whether by nurses working at the community level or by CHWs – was also effective [S32–34].E. coli concentration in water and decreasing episodes of diarrhea . The efficacy of community–based interventions concerning immunizations, HIV and nutrition are presented later in the respective sections.Purification of water within the household with sodium hypochlorite or another locally produced purifying agent was found effective in reducing childhood diarrhea in several studies [S35–38]. Solar sterilization of water was demonstrated as an effective approach to decrease the incidence of childhood diarrhea [S39–41]. Water filters such as BioSand and Lifestraw Family Filter that remove particulate matter were similarly effective in reducing the Malaria is one of the three commonest causes of child mortality in those countries where it is endemic. In Africa, malaria is the cause of 15% of under–5 mortality . Major cAs shown in There were several other assessments that provided evidence in support of the community–based distribution of impregnated bed nets for prevention of malaria [S62–68]. A commonly used approach which produced operationally important outcomes was combining the distribution of ITNs with measles vaccination at the time of mobile clinic outreach sessions [S69–72]. Combining distribution of ITNs with malaria treatment was also effective [S73–75]. Several studies provided evidence that impregnated curtains have some effectiveness in reducing all–cause child mortality . Some other studies focused on the use of ITNs but did not show as strong evidence individually [S78–83]. Studies which include prevention and treatment of malaria with Integrated Community Case Management of Childhood Illness (IMCI) or with other integrated approaches  will be presented later in this paper.The assessments included in While many of these studies of malaria treatment demonstrated a reduction in malaria–related morbidity or an improvement in CHW performance outcomes related to malaria, some demonstrated important decreases in overall child mortality as well . The cost-effectiveness of combining malaria and pneumonia treatment was studied. However, the findings were inconclusive [S95]. The demonstration of the capacity of CHWs to accurately diagnose malaria using RDTs is also an important finding [S56].Trained traditional healers and drug vendors can effectively educate mothers about malaria prevention and early treatment . Some other studies that focused on malaria treatment or IPT at the community level had results that were consistent with our findings above but the strength of evidence was not as strong [S99–111].There were fewer studies specifically on HIV/AIDS prevention and control at the community level. One study demonstrated that community–level treatment with co–trimoxazole of HIV–infected adults led to a reduction of 77% in the mortality of their originally HIV–negative, under–10 year–old household members. The provision of the drug and the monitoring of activities were provided by community members [S112]. Several studies reported on community–based HIV testing. One study found that among persons taking antiretroviral therapy, contacts that were visited at home were much more likely to undergo HIV testing than persons seen only at the health clinic [S113]. The prevention of mother–to–child transmission (PMTCT) was the most commonly studied HIV intervention in the assessments reviewed. As PMTCT is discussed in our maternal health paper, only a few examples will be mentioned here. In one study, the probability of survival of children to 18 months of age was 84% higher, compared to those in the control group, when HIV–positive mothers received antiretroviral medication as part of a comprehensive integrated program for HIV exposed infants [S114]. Household visits by CHWs, immunizations and growth monitoring were a part of this project.P = 0.01) [S118].The role of household visiting by CHWs was often found to be important for HIV–control projects. In one project, intensive follow–up care by CHWs at the homes of HIV–infected mothers led to much greater compliance with PMTCT and also with antenatal and postnatal care. Initiation of anti–retroviral therapy (ART) for HIV– infected infants was also earlier [S115]. Similarly, CHW home visiting was found to lead to a statistically significant 27% increase in identification of HIV–exposed and infected infants and attendance at health facilities [S116]. Community household visits by midwives who gave counseling and nevirapine to HIV–positive mothers and advised them to give nevirapine to their newborns within 72 hours of birth were found to decrease mother–to–child transmission of HIV by 60% [S117]. Community–based adherence support for 982 children on antiretroviral treatment was found to lead to 60% more children achieving virological suppression than children in the control group  and also carried out growth monitoring of children. Their activities led to a 150% increase in the coverage of 12–23 month–old children with full immunization [S124].Promotion of community participation through education of village leaders, teachers, and extension workers (who in turn educated community members) was found effective, increasing full immunization completion coverage levels by 50% [S125]. Mass media using TV, radio, newspapers and leaflets, distributed and explained by community–level workers, significantly increased community awareness about immunizations with mothers. Those mothers who had increased awareness were much more likely to take their children to be vaccinated [S126]. In Lao PDR, community–based workshops promoting attendance for vaccination significantly increased all childhood vaccinations [S127].A case–controlled study of community health education campaigns associated with microcredit programs were found to greatly increase fully immunization coverage [S128].National Immunization Days, in which community mobilization and immunization at peripheral service points followed up by immunization at the household for those who did not come to the service point led to significant decreases in the incidence of acute flaccid paralysis [S129]. Annual vaccination weeks with household visits by CHWs increased vaccination completion rates from 30% to 53% [S130].A case–controlled study of peer education provided by CHWs visiting households, promoting community involvement, and providing immunizations, vitamin A supplementation and growth monitoring led to not only to greatly increased immunization coverage but also to a 58% decrease in under–5 mortality compared to controls [S131]. House–to–house administration of polio vaccine significantly increased polio vaccination rates [S132].Undernutrition contributes to 45% of under–5 mortality globally  and therP < 0.05 level also were very informative. In Vietnam, among children aged less than 15 months with a weight–for–age Z score of <–2, the Hearth approach along with de–worming significantly improved growth when compared to controls who received only deworming [S143]. The Hearth approach is a process of identifying local “positive deviant” women who have well–nourished children. Mothers of malnourished children are also identified and they are guided through a process of learning how positive deviants care and feed their children and applying this knowledge in the care of their own children through hands–on cooking sessions using locally available foods [S143].Other controlled interventions with smaller effect sizes and statistically significant results at the P = 0.005 or less in all age groups). For the control group  the same comparison with younger siblings was carried out. The mean weight for age Z score of the younger siblings was always lower for mildly malnourished and normal weight children than their older sibling . This study provides evidence regarding the wider family effects of nutritional education [S144]. However any conclusions need to be guarded due to the limited size of the populations studied. These results would need to be repeated in further similar studies.In a non–randomized controlled project that was implemented over a five–year period, the hypothesis was tested that younger siblings of older children with severe undernutrition whose undernutrition had been overcome using the Hearth approach should have better nutrition than similar children whose mothers had not been exposed to the Hearth program. Outcomes were compared for 10 different 3–month age groupings of younger siblings . For younger siblings whose older sibling had been severely malnourished and whose mother had been exposed to the Hearth approach (the intervention group), the younger sibling mean weight for age Z score was always higher than the older sibling (P < 0.00001) [S146].The benefits of promotion of agriculture and voucher programs on childhood nutrition have also been demonstrated. In a population including 130 000 children younger than 5 years of age in Nepal, promotion of increased household production of food through training Village Model Farmers, and subsequently village women, led over a 2–year period to a decrease of 10% in the prevalence of underweight in children aged 0 to 4 years [S145]. A community development and livestock promotion project in Nepal for 307 children produced similar results. Although the results in the latter study were not statistically significant after 2 years, the intervention group was more likely to have indoor access to water, treat their water and have a latrine. Longer participation in the program was strongly associated with a better mean height–for–age score (P = 0.029) compared to controls of the same age [S147]. Other studies demonstrated a statistically significant association of mothers receiving vouchers with greater use of nutrition monitoring at the community level and improved nutrition of their children [S148–151].Giving vouchers to mothers along with health education and a community household health package was found not to result in statistically significant improved child nutrition in the short term but if the program for those children was extended for 2 years more until the children were aged 8 to 10 years, then the mean height for weight Z scores of these children increased by 23% (.Exclusive breastfeeding (BF) during the first 6 months of age with continued BF through the first two years of life is an important contributor to good childhood nutrition, reduced morbidity, and improved mortality in resource–constrained settings. Promotion of exclusive breastfeeding for the first 6 months of life has been estimated to be one of the most effective preventive strategy for saving the lives of young children in low–income settings . ComplemThe data from Types of micronutrient supplementation that were included in projects whose assessments qualified for our review included vitamin A, zinc, iron and multivitamins. Daily zinc supplementation decreased all–cause mortality in children 12–48 months of age, but not to the same extent as vitamin A. A decrease in the incidence of diarrhea in children receiving zinc has also been demonstrated in other controlled studies . Of particular note is that in one study of children 1 to <6 months of age in a malaria–prone area, the risk of death or severe morbidity increased significantly in those who received iron supplementation [S176]. While other studies in non–malaria–endemic areas confirmed the value of iron supplementation for treating anemia, this finding provides reason for caution in providing iron supplementation to children aged 1 to <6 months of age in malaria–endemic areas.Children present with a variety of common diseases even when one disease such as malaria may predominate in a particular area. Undernutrition is a common risk factor for childhood infections ,11. OppoIntegrated Management of Childhood Illness (IMCI) integrates the prevention and treatment of all childhood illness at health facilities. Its community component, called Community IMCI (or C–IMCI), usually consists of preventive activities and early recognition of potentially serious acute illness that can be performed in the community by trained CHWs going door–to–door and meeting with groups, usually without treatment of illnesses other than ORS for diarrhea. CHWs are taught to recognize children with danger signs and refer or even escort patients to the nearest health facility for treatment. CHWs also facilitate outreach activities from the local health center such as immunizations.Integrated Community Case Management (iCCM) enables CHWs to diagnose and treat serious acute illnesses of childhood .P < 0.001) and from 0.25 cases/1000 child–months to 5.28 cases/1000 child–months (P < 0.001), respectively. On average, total under–5 mortality rates declined significantly by 38% (P < 0.001), and health facility use declined significantly by 15%. These decreases were significantly greater than expected based on baseline trends [S192].For iCCM to be effective, CHWs need to be well–trained, to have the confidence and support of their community, to be well–linked to their local health facility staff for referral of patients, to receive regular supervision to maintain their skills, and to be well–supplied with the drugs and equipment necessary to perform their tasks . These CP = 0.001) increase compared with baseline levels [S188]. The other studies cited in In many parts of rural Uganda with limited access to trained health staff, up to 50% of cases of childhood illnesses are managed by drug sellers. One study in which private drug sellers were trained to treat patients using iCCM protocols revealed a strong adherence to the iCCM protocol in terms of testing, examining and treating children. On follow up evaluation after training, 88% of children diagnosed with diarrhea received ORS. 88% of children presenting with a fever received a RDT for malaria and 94% of children who were diagnosed as RDT–positive received artemisinin combination therapy. Of those who were diagnosed with pneumonia, 91% of them received amoxicillin treatment. Overall performance (defined as correct treatment) showed a 27%  since project activities began several years later in Area B after activities in Area A had begun. Major improvements were achieved across most indicators of child health comparing baseline with endline findings. Key outcomes were that the overall proportion of children with undernutrition (WAZ<–2.0 SD) decreased by 6% in Area A and by 10% in Area B; insecticide–treated bed net (ITN) use increased by 45% in Area A and by 71% in Area B; rates of exclusive breastfeeding increased by 60% in Area A and 25% in Area B; the percentage of children 9–23m of age who ate three or more meals per day increased from by 42% in Area A and by 20% in Area B. Based on findings obtained with the Lives Saved Tool (LiST), the project saved an estimated 6848 lives and the cost per life saved, the cost per disability–adjusted life year (DALY) averted, and the annual cost per beneficiary were US$ 441, US$ 14.72 and US $2.78, respectively [S193].Another Care Group project in the rural part of the Chokwe District in Mozambique also incorporated a community–based vital events registry system as part of the activities of the Care Groups. The assessment of this project demonstrated not only the efficacy of Care Groups but also the quality of a community–based vital events registration system. This assessment demonstrated that the Care Group approach resulted in a 49% decrease in the infant mortality rate and a 42% decrease in the under–5 mortality rate over the five year period of project implementation, confirmed by an independent retrospective morality assessment based on maternal birth histories [S194]. Similar results were found in another Care Group project in our database in Burundi [S195].Primary health care (PHC) includes the provision of a comprehensive range of essential preventive and treatment actions aimed at meeting all the common health needs of community members  using practical and affordable approaches. For integrated CBPHC to be effective at the community level outside of health facilities, CHWs need to have good linkages to the local health facility to which patients with severe illness, injuries and uncommon or more severe illnesses can be referred and where mothers can give birth. Services such as immunizations that require outreach from health facilities also need to be provided at the community level in order to make essential services readily available. Our review includes a number of community–based PHC programs that are presented in The census–based, impact–oriented (CBIO) methodology includes mapping and community registering to ensure that all beneficiaries are documented and included in the project information system so that they are included in all community–based PHC programs . The CBIO approach was pioneered in Haiti in the 1970s. Assessment by retrospective maternal birth histories and household anthropometric surveys demonstrated a 68% reduction in under–5 mortality and reduced prevalence of stunting compared to national rural indicators .The last assessment in One important study in our database that does not lend itself to incorporation into Key CBPHC aspects of this project were that Family Health Workers provided treatment in the home for dehydration from diarrhea and for childhood pneumonia. The children 0–3 years of age with pneumonia who were treated with penicillin had a 42% reduced risk of overall mortality [S206]. Other key findings based on a qualitative review of data were that: one–on–one education of mothers was essential for improving practices related to breastfeeding, infant feeding, rehydration and feeding of sick infants and also for overcoming traditional beliefs about not feeding a child with diarrhea; weekly home visits were necessary in order to achieve a reduction in infant mortality; delegation of services as far to the periphery as possible improved coverage and effectiveness; rehabilitation of malnourished children through special feeding programs was best accomplished at home or near the home; having a curative health care service was an essential element of building trust, and developing a quality health care program required active community participation and building trust with the community [S207].Several other assessments included in our database are of particular note since they document the evidence of the long–term benefits of CBPHC projects on child health. These projects are:The ICDDR,B MCH–FP Program in Matlab, Bangladesh ;The Hôpital Albert Schweitzer in Deschapelles, Haiti;The Jamkhed Comprehensive Health Project in Jamkhed, India; and,SEARCH  in Gadchiroli, India.These projects are discussed in detail elsewhere in this supplement .This review provides strong evidence that overall the major causes of child mortality in developing countries can be addressed at the community level outside of health facilities by working with communities and community–level workers. For all categories of interventions, we have presented findings from randomized and non–randomized controlled trials in our database that have consistently produced statistically significant and operationally important effects. In many cases the outcomes observed have been changes in the most objective and meaningful indicator: mortality.Some assessments, mostly unpublished child survival project evaluations, relied on before/after study designs without a comparison group, measuring changes in population coverage of key child survival interventions. In virtually all cases, the changes in coverage over a 4–5 year period were quite pronounced, particularly in comparison to much smaller changes in coverage in the regional or national population, as a review of a set of these projects has demonstrated . They haOur findings regarding the effectiveness of specific community–based interventions for improving child health are similar to those reported in other reviews ,17. The We have not addressed here three important questions: (1) who are the community–level workers who implemented the interventions, (2) what particular resources do they need in order to deliver the interventions, and (3) what are the conditions that would need to be met in order to scale up these interventions under routine conditions. Answering these questions is beyond the scope of this paper, and few assessments really address these questions, unfortunately. The degree to which the assessments included here represent efficacy studies  as opposed to effectiveness studies (implementation under routine field conditions) cannot be adequately explored here. However, it is clear that appropriately trained, supervised and supported CHWs along with engaged communities are needed to achieve effectiveness, and these conditions appear to have been met in the projects included in our review.This review demonstrates that four major strategies for delivering community–based primary health care interventions are effective and commonly used in projects that have improved child health. These strategies are (1) house–to–house visitation by CHWs; (2) community case management of childhood illness, (3) use of participatory women’s groups; and (4) outreach services provided in the community by mobile teams based at peripheral health centers. CHWs visit households to educate child caregivers about prevention and manage common illnesses. Through following well–developed protocols, CHWs link community members to their nearest health facility for management of serious illness or follow up. These strategies are discussed in detail elsewhere in this series from the perspective of CBPHC strategies for improving maternal, neonatal as well as child health .Many assessments included in our review support the importance of community engagement. A systematic review of child survival programs has found that programs working collaboratively with the community can lead to cost–effective transformation and lasting behavior change that produces improved health outcomes . As a reWhile we have made every effort to include all relevant studies that meet our criteria, some important studies have escaped our screening process. One such study concerns the use of pre–referral rectal artesunate . In a raSeveral studies included in our review confirmed the effectiveness of Integrated Community Case Management (iCCM) (P < 0.0001), the prevalence of febrile illness of children younger than 5 years of age was significantly lower, from 38% at baseline to 23% at endline (P = 0.0009) and the percentage of children starting an effective antimalarial with 24 hours of symptom onset was nearly twice that reported at baseline (P = 0.0195).As the Narangwal project demonstrated four decades ago, the provision of some curative care builds community trust in the CHWs providing it. It also facilitates referral to local health facilities as needed. However this trust is difficult to develop if the CHWs are not in regular contact with all households and if community members are not convinced that the CHWs are well trained and competent. One particularly important recent example of the effectiveness achieved by meeting these conditions occurred in Yirimadjo, Mali [S93]. The intervention included CHW active case finding, user fee removal, infrastructure development, community mobilization and prevention programming. After three years of the intervention, the hazard of under–5 mortality in the intervention area was one tenth that of baseline  approach and Care Groups have demonstrated the importance of registering and visiting frequently all households with mothers and children, as more recent evidence has also demonstrated ,27. The The following essential interventions for child health that can be provided at the level of the community and/or health post by CHWs have been identified :Promote breastfeeding (including exclusive breastfeeding during the first six months of life) and appropriate complementary feeding beginning at 6 months of ageProvide vitamin A and zinc supplementationProvide co–trimoxazole for HIV–positive childrenEducate families on safe disposal of children’s stools and hand washingDistribute and promote use of ITNs or IRs or bothDetect and refer children with severe acute malnutritionPrevent, diagnose and treat of pneumonia, malaria and diarrheal diseases with early referral of those children with danger signs of serious disease.The strong and consistent evidence that we have presented in this paper clearly demonstrates that all these Essential Interventions can be delivered at the community level with favorable population–level results for children.The findings from this review also provide strong evidence that the four key strategies of delivering community–based interventions are effective approaches for achieving implementation effectiveness through CBPHC. These strategies are: (1) house–to–house visitation by CHWs; (2) community case management of childhood illness, (3) use of participatory women’s groups; and (4) outreach services provided in the community by mobile teams based at health centers. We have also presented evidence that community participation and mobilization make a strong contribution to intervention effectiveness.Some of the studies included in our review lacked sufficient information about the assessment methodology, about the role of community members and other implementation strategies, as well as about the outcomes themselves. This sometimes made it difficult to assess the strength of the evidence and to draw firm conclusions. We worked to mitigate this limitation by, in some cases, following up with the authors of these assessments.Due to space limitations not all 489 assessments of the effectiveness of CBPHC in improving child health could be cited in this analysis. However, the findings of the assessments not specifically cited here are consistent with and supportive of those that were cited.As is well–known, project failures and serious challenges encountered in program implementation are rarely described in open–access documents or in the scientific literature. This means that a serious publication bias is present and should be recognized. Nonetheless, publication bias does not negate the value of the numerous assessments that have been included in our review that demonstrate effectiveness of CBPHC in improving child health. The consistency of findings across many assessments in relationship to most interventions is such that we are convinced that the general findings with respect to each specific intervention are valid.We acknowledge that there may be some assessments that qualified for our review that were not picked up by our screening procedures. However, we do not think that the inclusion of any articles we might have missed would alter the overall findings from our review. In addition, we are aware that there are important findings in papers published after December 2015 that did not fit the timeline of our review, but we have highlighted them in the discussion.Our review has identified several areas of further study that are needed to address gaps in current knowledge to improve the implementation of child health programs at the community level. These areas are:Effectiveness studies of the implementation of community based interventions at scale in large populations in routine settings for 5 or more years;Effectiveness studies on how best to involve communities in the monitoring, implementation and evaluation of these settings.As can be readily seen from the tables in this paper there is a clear lack of assessments of studies of interventions in large populations at scale. In the final paper of this series  the ExpeGiven the heterogeneity of (1) the types of interventions implemented, (2) the manner in which they were implemented, and (3) the outcome measures used to assess outcomes, it is not possible to make any definitive statements about the strength of the evidence or the magnitude of effect for any specific intervention or any specific approach to implementation, or how any given intervention or implementation approach compares with another in terms of effectiveness. Moreover, addressing the important issue of how to most effectively integrate interventions into a balanced package of services so that the demands for implementation of one intervention do not override the requirements for implementation of another intervention is beyond the scope of this paper, as is the important issue of how to strengthen health systems more broadly to better support the implementation of effective CBPHC interventions for improving child health.Nonetheless, consistent with the purpose of our overall review of the effectiveness of CBPHC in improving MNCH, our overall findings strongly support the conclusion that (1) CBPHC can in fact be effectively implemented at the community level to improve child health and (2) robust community–based delivery systems are needed in order for the evidence–based interventions currently known and those that will be developed can reach their full potential.We have presented the evidence of effectiveness of a broad range of community–based interventions for improving the health of children 1–59 months of age. Health systems that are capable of achieving universal coverage of these interventions in high–mortality settings are clearly needed. Achieving this capability will require strong support for the health system as well as a strong commitment to a well–trained and well–supported CHW cadre in sufficient numbers. Understanding the conditions that need to be met in order for these interventions to be effective at scale in routine settings in priority countries and ensuring that these conditions are met will be the major challenge in the decade to come.


Here, we model the progressive dilution of the radiocesium contamination in 327 sediment samples from two neighboring catchments with different timing of soil decontamination. Overall, we demonstrate that there has been a ~90% decrease of the contribution of upstream contaminated soils to sediment transiting the coastal plains between 2012  and 2015 . The occurrence of typhoons and the progress of decontamination in different tributaries of the Niida River resulted in temporary increases in local contamination. However, the much lower contribution of upstream contaminated soils to coastal plain sediment in November 2015 demonstrates that the source of the easily erodible, contaminated material has potentially been removed by decontamination, diluted by subsoils, or eroded and transported to the Pacific Ocean.Fallout from the Fukushima Dai-ichi nuclear power plant accident resulted in a 3000-km The only significant difference between these catchments is a major dam located between the upstream – more contaminated – section of the Mano catchment and the coastal plain – where soils contain very low radiocesium concentrations  to 2015 M 10%; . The proThe sediment disconnectivity induced by the Mano Dam (with the exception of a major dam release that occurred in 2011) provides an opportunistic method to estimate the decrease in upstream contaminated soil median contributions (from 68% to 6%) that would have been observed in the coastal plains of the Niida catchment in the absence of continuous supply of contaminated material originating from upper catchment parts . After sWhen the model results are grouped for each upstream tributary of the main Niida River, the evolution of the contaminated soil contribution is different than what was observed for the entire upstream Niida catchment . The medThese results illustrate the strong spatial and temporal variability of radioactive contamination levels of sediment transiting the Niida and the Mano Rivers between 2011 and 2015. This is likely explained by the occurrence of various erosion processes in the catchment and the collection of sediment deposits in different hydro-sedimentary contexts. Despite these spatial differences and the uncertainties associated with the model results, there is a major decrease in sediment contamination levels during this period. This trend is relevant with other observations reported in the literature618In particular, during the first two years that followed the nuclear accident, it was estimated that 1–5% of the initial catchment radiocesium inventory was exported by Fukushima coastal rivers to the Pacific Ocean1921Thereafter, the export of radionuclides bound to sediment is much slower, and should not exceed 1% of the initial radiocesium inventories in soils according to the estimations available from the literatureThere were sediment-bound radiocesium peaks evident that were directly related to decontamination works. Although this increase is associated with large uncertainties, our modelling results suggest that remediation efforts may lead to a temporary increase in these levels during or shortly after the start of these operations. This may be explained by the fact that vegetation is removed to prepare these worksIn general, Fukushima river systems appear to be very reactive to both rainfall events  and the The very low proportions of contaminated soil median contributions modelled in sediment collected in November 2015  indicate that the most erodible contaminated soils have already been flushed away to the Pacific Ocean. Although contaminated material is likely stored for a long time in the major dam in the Mano River catchment, the supply of contaminated sediment is more and more unlikely in catchments where remediation works have been completed.In future, the potential contribution of forests as a perennial low-magnitude source of radioactive contamination to the river systems should be investigated, as forests cover two-thirds of the surface area in this region. Although both subsurface sources were also modeled as a depleted radiocesium source owing to the paired catchment design, the relative contributions of subsurface sources and decontaminated sources should be examined through the application of a different suite of appropriate fingerprints.2) and Mano (175 km2) catchments (137Cs) inventories ranging from 20 kBq kg−1 to 75 kBq kg−1. In contrast, soil radiocesium inventories in the lowland coastal plains were less than 20 kBq kg−1 This research was conducted in the Niida  were collected between 2011–2015 in locations reported to be highly connected to the stream network2 quadrant using a non-metallic trowel and composited into one sample. Second, 137Cs activities were included for 100 soil samples collected in these two catchments in June and July 2011 by the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT)n = 44 in the Mano and n = 42 in the Niida catchment). Contaminated source sample distributions were derived from samples taken in the upstream areas (>100 m elevation n = 118 in the Niida catchment).Two approaches were used to develop a Nine sediment sampling campaigns were conducted between November 2011 and November 2015. Sampling occurred bi-annually at 41 locations: in fall after the typhoon season, and in spring, after the snowmelt runoff. The goal was to sample deposited sediment that was transferred during these main erosive periods. In total, 327 sediment samples were obtained. Fine sediment samples were taken from material deposited after the last major event at the same sites, during each of the nine campaigns. These lag deposit samples were comprised of fine particulate material that settled on channel banks, inset benches and floodplains during the falling limb of the last significant hydro-sedimentary event. Ten subsamples (~5 g per subsample) of recently deposited material were taken with a plastic spatula over a 5 m reach and composited into one sample.137Cs activities were determined with gamma spectrometry using coaxial N- and P-type HPGe detectors (Canberra/Ortec). 137Cs activities were measured at the 662 keV emission peak. More information on these methods can be found elsewhereAll samples were dried at 40 °C for ~48 h, sieved to 2 mm and ground to a fine powder in an agate mortar, and pressed into 15 mL polyethylene containers for measurement. 137Cs). A summary of radionuclide activities characterizing both source types in the Niida and Mano catchments is provided in A distribution modelling approach was used to incorporate distributions throughout the entire modelling framework, including the source contribution termsx, and the contribution of B being 1−x where:For the two-source model, it is assumed that sediment samples constitute a discrete mixture of their sources, with the source contribution of A being C is the in-stream sediment distribution, A and B are the two source distributions, and x is modelled as a truncated normal distribution (0 ≤ x ≤ 1) with a mixture mean (μm) and standard deviation (σm)C and Ax + B (1 − x)) with the Optquest algorithm in Oracle’s Crystal Ball software with a randomly generated mixture mean (μm) and standard deviation (σm).The two source distributions were fit with the Crystal Ball software which selected the optimal distribution based on the results of three statistical tests: Anderson–Darling, Kolmogorov-Smirnov and Chi-Square. For the depleted source distributions in both catchments, log-normal distributions were modeled and for the contaminated sources, Maximum Extreme Distribution  were modeled.m) and standard deviation (σm). This model simulation and solving process was then repeated 2500 times with the median proportional source contribution from these 2500 additional simulations, reported as the contribution of each source. Model uncertainty was calculated through summing three quantifiable model uncertainties: (1) the median absolute deviation of the individual source median contribution for the additional 2500 simulations; (2) the modelled standard deviation; and (3) the median absolute deviation of this modelled standard deviation for the 2500 model additional simulationsSource contributions (x) were determined by simulating How to cite this article: Evrard, O. et al. Quantifying the dilution of the radiocesium contamination in Fukushima coastal river sediment (2011–2015). Sci. Rep.6, 34828; doi: 10.1038/srep34828 (2016).


Echinococcus granulosus in its larval stage which is endemic in many parts of the world including Saudi Arabia. The disease can produce a cyst in almost every part of the body with the liver and lungs being the most frequently targeted organs producing a variety of symptoms depending upon the site and size of the cyst. We report a case of giant hepatic hydatid cyst with the possibility of renovascular hypertension due to mass effect as evident by dramatic drop of the blood pressure to its normotensive state postoperatively.Renovascular hypertension is an unusual but treatable cause of refractory hypertension that is infrequently caused by external compression of the renal vasculature by a giant hydatid cyst, a parasitic infection, caused by  Echinococcus granulosus(E. granulosus) in its larval stage [Renovascular hypertension is an unusual but treatable cause of refractory hypertension that is infrequently caused by compression of the renal vasculature by a giant hydatid cyst. Cystic echinococcosis (CE) is a parasitic illness caused by infection with al stage . The tapal stage , and theLarvae emerge from the eggs in the intestine, and after invasion to the blood vessels, they can migrate into almost every part of the body . The mosLarge cysts, today fairly rare even in endemic areas, are called giant hydatid cysts (GHCs) , 5. HepaA 24-year-old native Arabian lady, mother of four, from the high mountainous area who was managed by a local primary healthcare centre as a case of essential hypertension, was referred to the medical outpatient department of our secondary care facility for uncontrolled hypertension for the last few months. After primary assessment, the medical team put her on antihypertensive medication and sent back home. On the next visit, her BP remained high despite combined antihypertensives with ACE inhibitor, beta-blocker, and Ca-channel blocker and complaining of right hypochondrial pain, for which ultrasonography was requested along with basic laboratory workup.U/S shows a large cyst in the liver for which the patient was referred to surgical OPD for consultation. The surgical team decided for elective surgical exploration.On admission, the patient vitals were stable except high BP of 155/91 mmHg and high ALP (221 U/l).Ultrasonography showed a maternal right liver lobe hydatid cyst measuring 14 × 16 cm, and CT scan revealed a large sizable hypodense cystic lesion of about 150 × 150 × 200 mm in AP × TS × CC dimensions, respectively, with multiple septations inside, being mainly in the right lobe, with peripheral calcific wall seen laterally with normal liver parenchyma , occupyiMost patients with a hydatid cyst in the liver are asymptomatic, and its presence becomes evident only when the liver is found to be enlarged or a cystic lesion is noted when the liver is imaged for any other reason . In the In conclusion, the mass effect of a giant hepatic hydatid cyst should be kept in mind as one of the unusual causes of hypertension when dealing with the patient where hydatid disease is endemic and the patient is refractory to antihypertensive medications.


However, present understanding of the TADF mechanism does not extend far beyond a thermal equilibrium between the lowest singlet and triplet states and consequently research has focused almost exclusively on the energy gap between these two states. Herein, we use a model spin‐vibronic Hamiltonian to reveal the crucial role of non‐Born‐Oppenheimer effects in determining krISC. We demonstrate that vibronic (nonadiabatic) coupling between the lowest local excitation triplet (3LE) and lowest charge transfer triplet (3CT) opens the possibility for significant second‐order coupling effects and increases krISC by about four orders of magnitude. Crucially, these simulations reveal the dynamical mechanism for highly efficient TADF and opens design routes that go beyond the Born‐Oppenheimer approximation for the future development of high‐performing systems.Factors influencing the rate of reverse intersystem crossing ( The communication between low‐lying singlet and triplet excited states is of great importance in the field of organic electronics and plays a fundamental role in determining key molecular and material properties such as the lifetime and mobility of charge‐separated states.For the latter this has particular significance owing to the emergence of thermally activated delayed fluorescence (TADF).Adachi and co‐workersDespite the intense research interest and obvious promise of TADF materials, it is astounding that the reverse intersystem crossing (rISC) process, crucial to TADF is not fully understood. This absence is important for achieving rational material design and especially given the widening scope of TADF in applications such as fluorescence imaging.kTADF), that is, rISC proceeded by fluorescence as :3LE and 3CT promotes, on a timescale much faster than the rISC , an equilibrium between the two states. Obviously, the position of this equilibrium depends both on the size of the vibronic coupling and the energy gap. Subsequently, the second‐order term, Equation (7), couples the 3CT and the 1CT, using the 3LE as an intermediate. This latter second‐order term is very efficient because of the good vibrational overlap between the almost degenerate initial and final states, 3CT and 1CT, respectively. Therefore, the two coupling terms driving this dynamics are the SOC and the vibronic coupling elements. This explains recent experimental results which demonstrated that steric hindrance of D–A dihedral angle switches the main pathway from TADF to phosphorescent.Equations (6) and (7) indicate a two‐step mechanism. Firstly, the large vibronic coupling between 3LE to 3CT is required. This is then followed by a direct second order coupling via the initially populated 3LE state. For the latter two examples  should be addressed to the authors.SupplementaryClick here for additional data file.


This finding was reached by using an unprecedented ligand‐based prediction platform and the natural product piperlongumine as a pharmacophore probe. (−)‐Englerin A features high substructure dissimilarity to known ligands for voltage‐dependent Ca2+ channels, selective binding affinity for the dihydropyridine site, and potent modulation of calcium signaling in muscle cells and vascular tissue. The observed activity was rationalized at the atomic level by molecular dynamics simulations. Experimental confirmation of this hitherto unknown macromolecular target expands the bioactivity space for this natural product and corroborates the effectiveness of chemocentric computational methods for prioritizing target‐based screens and identifying binding counterparts of complex natural products.The voltage‐dependent L‐type Ca From a computational point of view, the successful off‐target identification can be ascribed to the topological pharmacophore descriptors and consensus self‐organizing map method implemented in SPiDER, in contrast to the substructure‐based fingerprints implemented in other tools. Whereas natural products display different architectures compared to lead‐like molecules, their potential pharmacophore features are sufficiently similar to those of drug‐ and lead‐like molecules to allow confident target inferences.Natural products remain an important source of chemical matter in drug discovery. Nonetheless, their value as chemical probes requires extensive validation and exploitation of on‐/ off‐target engagement effects and systems biology. (−)‐EA has recently attracted considerable attention in cancer research. We experimentally confirmed the validity of our pioneering target‐prediction concept. We disclose functional effects of (−)‐EA on CaIt is noteworthy that false‐positive predictions are still expected with this or related platforms, and only previously liganded macromolecules can be discovered as on‐ and off‐targets for the query natural products. That said, the results suggest an expeditious chemogenomics‐inspired platform to rationally steer screening efforts and unveil hitherto unknown pharmacology for complex chemotypes lying outside of drug‐like space and thus outside of the domain of applicability of current state‐of‐the‐art and publicly available target‐prediction tools.Ultimately, we foresee a broad scope and prime utility of related technologies to identify unexpected, although much sought after, polypharmacology networks for intricate natural products, and to leverage the design of natural product inspired entities for chemical biology and molecular medicine.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


X, Y, Z)(T) coordinates representing a motion kernel into a software application thattransformed the kernel into beam‐specific two‐dimensional (2D) motion “projections,”previewed the motion in real time, andX–Y motorized device that had, atop it, a mounted planar IMRT QA measurement device.drove a precision Emerging technologies such as four‐dimensional computed tomography (4D CT) and implanted beacons are expected to allow clinicians to accurately model intrafraction motion and to quantitatively estimate internal target volumes (ITVs) for radiation therapy involving moving targets. In the case of intensity‐modulated (IMRT) and stereotactic body radiation therapy (SBRT) delivery, clinicians must consider the interplay between the temporal nature of the modulation and the target motion within the ITV. A need exists for a 4D IMRT/SBRT quality assurance (QA) device that can incorporate and analyze customized intrafraction motion as it relates to dose delivery and respiratory gating. We built a 4D IMRT/SBRT prototype device and entered  were defined as “target detectors” to be analyzed for dose uniformity between multiple fractions. Data regarding the use of this device to quantify dose variation fraction‐to‐fraction resulting from target motion  have been recently published. A combined software and hardware solution for patient‐customized 4D IMRT/ SBRT QA is an effective tool for assessing IMRT delivery under conditions of intrafraction motion. The 4D IMRT QA device accurately reproduced the projected motion kernels for all beam's‐eye‐view motion kernels. This device has been proved to• effectively quantify the degradation in dose uniformity resulting from a moving target within a static planning target volume, and• integrate with a commercial respiratory gating system to ensure that the system is working effectively.Such a device is discussed as a potential tool to optimize the gating duty cycle to maximize delivery efficiency while minimizing dose variability.PACS numbers: 87.50.Gi, 87.53.Dq, 87.53.Kn, 87.53.Mr, 87.53.Tf, 87.56.Fc, 87.58.Sp The prescription, treatment planning, and dose delivery of intensity‐modulated radiation therapy (IMRT) are inherently customized. The process of IMRT treatment planning includes definition of target volumes and margins, critical volumes, dose distribution, immobilization devices, and delivery parameters that are specific for each patient's anatomy and treatment goals. Until recently, the treatment planning and delivery process would always assume a “rigid body” patient anatomy. Even today's per‐fraction image‐guided radiation therapy (IGRT) practices result in daily patient repositioning to give the optimal target location relative to the treatment isocenter or isocenters.Newer technologies, such as 4D respiratory‐gated CT or implantable, traceable markers, are allowing a new degree of customization in the realm of treatment planning and delivery: the customization of a target motion envelope or “internal target volume” (ITV). These new tools allow for new strategies to handle the clinical reality of repeatable intrafraction target motion—more specifically, respiratory motion. Of particular importance is hypofractionated stereotactic body radiation therapy (SBRT), for which fractions can be much longer but also fewer in number, making tumor coverage even more critical. One general strategy is to prescribe dose to the planning target volume (PTV) and to make best efforts to minimize interplay effects. Another strategy is to use delivery gating techniques to treat during a specific subset of the period of motion, with the duty cycle directed around the time of least target movement. These strategies—ITV‐based prescription and gated delivery—can be used in various combinations.(–) A useful device would allow forassessment of fraction‐to‐fraction dose variation for a given ITV and intensity‐modulation technique;selection of the safest delivery option—step‐and‐shoot multileaf collimation (SMLC), dynamic multileaf collimation (DMLC), compensator‐based IMRT, and so on—for any given patient;determination of the optimal ITV;data‐driven decisions on whether gating is required, and the optimal duty cycle;patient‐specific verification and QA of delivery gating; andpre‐treatment dry runs to consider practical data such as delivery times, especially for hypofractionated treatment.As this new level of patient customization enters clinical practice, an appropriate 4D dose QA device must arrive in lock‐step. The American Association of Physicists in Medicine (AAPM) Task Group 76–4 A The ideal 4D dose QA device can be imagined. It would have a large number of very small (sub–cubic millimeter), isotropic‐responding, absolute dose detectors embedded as a three‐dimensional (3D) array in a water‐equivalent phantom. Internal subvolumes of this ideal device could be programmed to move as a function of time, perhaps even to move independently to allow for the simulation of deformation of the rigid body precept. Or, without any physical movement, a 3D array of real‐time signals could be used to reconstruct the cumulative dose to hypothetical dynamic tumorlets. Such a device could be used for any treatment modality . If the detector density was sufficient, measured dose–volume histograms (DVHs) could be estimated by treating the detectors as small voxels of tissue and dose.The ability to reproduce cyclical motion similar to human respirationIntegration of a gating surrogate that uses the same method as clinical treatment gatingAttachment of adequate dose detectorsPractical reliability and costHowever, although postulating an ideal device of the future is always important, providing evolutionary devices that can be practically used today is equally important. Technological, clinical, and practical requirements must be considered before all else when designing clinical tools. The AAPM TG‐76 report generalizes some requirements for a 4D QA device. For example:In the present work, we propose an actual device that meets these general requirements, plus more specific requirements. Particularly,  This device meets the key qualifying requirements for 4D development, as defined in 2 area (requirement 3). Furthermore, the device can be calibrated to quantify absolute dose (requirement 4), and it features the common toolset for IMRT QA data analysis (requirement 8).We chose to work with an existing commercial IMRT QA device, the MapCHECK diode array , which has been carefully analyzed for conventional IMRT QA.,6 ThOther commercial devices were considered. Two‐dimensional ion chamber arrays certainly satisfy requirements 1, 3, 4, 7, and 8, but are more limited with respect to requirement 2 (detector size and resolution). With high gradients and potentially rapid motion, submillimeter resolution is desirable, and this resolution is not possible with commercial ion chamber devices. Electronic portal imaging devices (EPIDs) show much promise in IMRT QA, and these were also considered. They have excellent detector density (requirement 3) and also satisfy requirements 1 and 8, which are of great importance. However, use of EPIDs for IMRT QA is still in the very early adoption phase, and no commercial offering yet has an absolute dose calibration, thereby hindering requirements 7 and 4. Additionally, the EPID devices would have either to be programmed to move rapidly during acquisition or else to electronically map dose to moving vectors of pixels on a stationary 2D array.The diode array therefore seemed most practical for this study. The remaining requirements—namely, the customizable, programmable motion (requirement 5) and integration with gating methods (requirement 6)—are developed in this study.Common conventional IMRT QA methods rely on creating verification dose planes for each beam. The treatment planning system calculates a patient beam on a flat water‐equivalent phantom, and a dose cross‐section is then extracted. An analogous plane of dose is measured with the detector array or film for comparison.This familiar 2D methodology can be extended to analyze 4D target‐motion studies, provided that the detectors that map to a target in each beam can trace out the BEV motion trajectory. In our case, a group of diodes (“target detectors”) that correspond to beamlets that intersect the radiation target needed to physically move, tracing what each beam would “see” from its reference frame during the intrafraction motion.X–Y motion device . The first key component was a motion controller (NSC‐M Series) to provide power and independent signals to the multi‐axis steppers. The next critical components were two independent linear stages (NLS4), each with 0.13 μm resolution, maximum travel speed of 5.08 cm/s, maximum acceleration of 72 cm/sX and Y. X–Y steppers below the diode array. A mount was built to fix the MapCHECK device securely atop the X–Y motion table. Equivalent buildup of 2g/cm2 and 5g/cm2 were tested for motion reproducibility for actual respiration motion kernels.To achieve this movement, we used a programmable To examine realistic clinical conditions, 4D respiration‐correlated CT studies  were analyzed to quantify motion kernels for two SBRT patients. The multiphase 4D image sets were transferred into a research module of the Pinnacle in centimeters as a function of time in seconds . Then, for each beam, the corresponding gantry and couch angle would allow the 3D motion kernel to be projected to the detector plane for any beam's specific BEV geometry. The collimator angle was not used in the transformation, because any collimator rotation could be executed for the actual QA measurements.A software application  represent coordinates transformed to a beam coordinate system with the origin at the isocenter; γ is the gantry angle, with nominal angle of zero , increasing as the gantry rotates clockwise; θ is a couch angle, with nominal angle of zero (into gantry), increasing as the couch rotates clockwise (viewed from above); and  is the actual BEV projection to the detector plane [source‐to‐detector distance (SDD)].AT time intervals from the respiration‐correlated CT study. The controller was operated in “vector‐motion mode” to ensure that the destination points and destination times were achieved with maximum accuracy without the need to program the complicated velocity and acceleration functions. Vector‐motion mode was an option afforded by the selected prototype hardware and software. Doses to the target detectors were tracked during dose delivery by the diode array acquisition software.The conversions to BEV coordinates for any beam, considering gantry angle, couch angle, and source‐to‐detector distance are outlined next. Variables X,Y,T) points are reached accurately when possible within hardware constraints, and therefore the constraints must be examined prospectively and with brute force calculation. This examination was achieved by first estimating the 2D acceleration and velocity vectors that would connect the various phases of the cycle for the first  loops.It should be noted that the software was programmed to alert the user if the acceleration or speed limits of the controller and steppers were to be exceeded. The “vector‐motion mode” previously described ensures that the  to  was estimated using the relationship of equation X,Y,T) data point. If any of the estimated velocity values exceeded the hardware maximum speed limit, an alert was issued, and the user given the option to “repair” the kernel by changing the T values to achieve allowable limits. No motion kernels in this study required repair.The first cycle starts from a stop; subsequent loops return to the starting point with non‐zero velocity vectors that become nearly identical for all cycles beyond the first. The velocity necessary to drive from any point Ti is the time in seconds at the programmed trajectory point ;Vi is the uniform velocity in centimeters per second that is achieved between points i and i+1;A is the fixed acceleration limit in centimeters per second squared; Pi is the linear position in one of the independent stepper directions  at the programmed trajectory point i;PiA is the position between points i and i+1 where the velocity becomes constant and the acceleration stops (centimeters); and ΔTiA is the time needed to accelerate from Vi−1 to Vi in reaching position PiA (seconds).Vi using the quadratic formula, yieldsX and the Y steppers.In the equations that follow, seconds).PiA=Pi+(VA•ΔTiA2)ΔTiA=(Vi−−Vi−1)/AVi=(Pi+1−Open fieldDMLC (sliding window)To show proof‐of‐concept of the device, two different SBRT plans were created for one lung tumor and motion kernel. Each plan had the same prescription, but they used different methods of delivery:The purpose of this experiment was to see if the 4D IMRT/SBRT QA device could detect interfraction variability in the irradiation of a moving target, and if the variability differed between the two delivery methods.The SBRT plans were generated with the PinnacleThe device was integrated with the Real‐time Position Manager  respiratory gating system. This system uses a video camera mounted in the treatment room to automatically detect motion of two markers on the external marker block. In a clinical situation, the marker block is placed on the patient using marks obtained during the 4D CT acquisition, and it moves up and down corresponding with inhalation and exhalation respectively. The treatment duty cycle is defined as a subset of the full up‐down motion, usually around the point of maximum exhalation.With the 4D IMRT/SBRT QA device, inhalation and exhalation corresponded to movement along the longitudinal axis of the couch. For a patient positioned with head toward the gantry, maximum inhalation (diaphragm most inferior) was mapped to the point when the motion kernel was farthest away from the gantry. Conversely, maximum exhalation mapped to the most superior point of the motion kernel. To create the corresponding up or down motion of the marker block, an appropriate wedge apparatus was constructed . As can This apparatus creates a gating trace that is not the patient breathing trace, and yet is an appropriate surrogate for the target motion. Even though this design does not yet reproduce actual patient breathing traces, the method is sufficient  from the SBRT plan so as to study the usefulness of the measurement device. First, we measured the planar QA dose for irradiation over the full breathing cycle  using a Varian 600C linear accelerator with 120‐leaf MLC. To quantify the variability between identical fractions attributable to the motion of the target, each delivery was repeated 10 times, starting each time at a random point in the motion cycle. We then repeated the irradiations using the amplitude gating method on a Varian 2100iX linear accelerator, gating with a 30% duty cycle centered on maximum exhalation.To study interfraction dose variation to the clinical target volume (CTV)–in–motion, it was necessary to determine which of the target detectors corresponded to beamlets that intersected the CTV. The treatment planning system was used to create a BEV projected to the isocenter plane for the maximum exhalation phase of the 4D CT. We overlaid that BEV on the detector array to map the diodes that would be analyzed. The SBRT target volume was relatively small, and therefore only 7 target detectors had to be analyzed.For the analysis, the measured dose for each diode was binned in a histogram for the 10 irradiations. Because the beams were intensity‐modulated, the best way to quantify variation between the fractions was to use the coefficient of variation, which is the standard deviation of the measurements for each diode over 10 samples as a percentage of the mean value of that set. We calculated the coefficient of variation for each target detector using the formulaFor SBRT1, plan beam of gantry 180 degrees, the PTV (ITV plus setup uncertainty) and interior moving gross tumor volume (GTV) are shown in X,Y) point in the BEV was reached with perfect accuracy, thus avoiding any positional drifts. However, although guaranteeing spatial accuracy, vector‐motion mode can cause minor, consistent deviations in the time period of each cycle . It was important to quantify these shifts to see if they were significant. We achieved this quantification by running the motion over many cycles  and then having the hardware report back the exact time versus the nominal time at the origin of each motion kernel. The recorded time drifts were each less than 0.01% of the total period. It was important to verify that the motion was accurate and reproducible over many cycles. The first prototype of the product used a motion method that computed the necessary accelerations and velocities to move from point to point in the kernel. This initial method exhibited drifts of several millimeters over 10 minutes of constant motion. We then modified the instructions to the controller to work in “vector‐motion mode” which ensured that each  with negligible differences. For example, the time drift for the 6.8‐kg load was intrafraction target motion or dose blurring, andinterfractional differences because of the random interplay of MLC motion and target motion.The first goal of the measurements was to see if the 4D IMRT/SBRT device could quantitatively analyze the variation and degradation in target dose attributable toToday's IMRT QA relies primarily on the technique of “dose to a plane” in water‐equivalent media, and there was practical value in preserving that method. But in the 4D case, the target detectors were able to move during delivery, because the beam would “see” the movement of the target motion kernel.3D (non‐IMRT) fieldsSolid compensator‐based IMRT (SIM)SMLCDMLCTarget detectors were tracked and analyzed to compare the fraction‐to‐fraction variation for non‐gated and gated delivery of DMLC‐based IMRT. These applications show the device and method to be very effective for quantitative analysis comparing modalities  and gated versus non‐gated delivery.The ability and ease with which preliminary results for clinical SBRT beams could be generated suggests that our model of a 4D IMRT/SBRT QA prototype device is effective. The device met all the criteria described in the introduction for an immediately applicable tool for the clinic that foresees planning using 4D CT image sets and dose delivery using IMRT or SBRT techniques. The device is especially useful for clinicians who utilize respiratory gating.However, to stringently assess the potential of such a device, an objective discussion of practical clinical usefulness is necessary. The question at issue is “What information does this device provide that will help to prove or disprove the accuracy and the safety of patient treatment?” We devote the Discussion to this important question, and we propose a potential decision flowchart for 4D IMRT/SBRT QA, as shown in For clinics that do not have gating technology for treatment delivery, our device could generate data to help answer critical questions about the patient plan and delivery technique. For example, if the motion kernel data are used to define an ITV, does that ITV receive appropriate dose reproducibility, fraction‐to‐fraction, given the intrafraction motion and delivery technique? Might the target have so much variability that the goal of eradicating the clonogens is put at risk? These questions are especially critical for hypofractionated SBRT treatments, which have higher dose per fraction and few fractions. The efficacy of such treatments is far less tolerant of dose variability. By using the 4D IMRT/SBRT QA device proposed here, clinicians can prospectively quantify the intrafraction dose blurring and the interfractional variation. The clinician would therefore be empowered with data either to confidently go forward with treatment or else to stop to consider different treatment parameters, such as the delivery modality, field complexity, or breathing motion–limiting techniques.In the case of clinics that do have gating technology for treatment delivery, this device will verify that the gating tools are working to give good dose reproducibility, fraction‐to‐fraction. Moreover, clinician will have a “dry run” to understand how long delivery of each field will take, which is very important for the scheduling of SBRT and complicated IMRT treatments for moving targets. Finally, and perhaps most interestingly, this device can serve as a tool to optimize the duty cycle of the gated deliveries—that is, it helps to answer how to achieve adequate dose reproducibility and coverage but with the most efficient duty cycle possible.Furthermore, if a clinic with gating tools wishes to use them only when necessary, then the 4D IMRT/SBRT QA device would help in making decisions about which patients, plans, and beams require gating to achieve acceptable dose coverage. For example, a clinic could set a threshold average coefficient of variation for the target detectors. If the average coefficient of variation exceeds the threshold, gating would be employed; if the variation is under the threshold, no gating would be necessary. Each clinic would have to weigh their clinical standards and practical resources to set their requirements.Important to the discussion of QA of gating effectiveness is the fact that this device always produces perfect correlation between the RPM markers and the detector positions. However, with actual patients, the marker and the tumor position will not be perfectly correlated.that a target's motion kernel loops with no variation in spatial trajectory or temporal period, andthat quantifying variation in the target detectors is relevant to dose variation in the patient.Of course, the use of the 4D QA device inherently makes two assumptions that could be debated:Regarding the first assumption, it should be remembered that the analog of the conventional 3D IMRT plan inherently assumes a rigid body patient model. Knowing full well that the rigid body precept is questionable at best with regard to patient anatomy, clinicians use CT simulation, immobilization devices, and IGRT to minimize errors, and they rely on target volume margins to account for the rest. In the same way, when we invite 4D image or motion data into the planning process, efforts must be made to minimize variation and to reproduce planning situations as best as possible. This approach particularly includes efforts at obtaining the 4D CT scans under conditions in which the motion will be cyclical and reproducible in treatment fractions. This goal is a considerable one, and we refer readers to AAPM TG‐76 for many useful suggestions and references.The second assumption  must also be understood in context. In fact, this method is already the prevalent one in use for most conventional IMRT QA using film, diode arrays, and ion chamber arrays. Of course errors between measured and calculated planar doses do not directly quantify what is really wanted: specific knowledge about the resulting deviation in tumor and normal organ voxels and corresponding DVH differences. However, beam‐by‐beam IMRT QA can be an effectively stringent method if appropriate acceptance criteria are enforced. When expanding to 4D motion models, 2D BEV‐based analyses cannot take into account the potentially changing radiologic path lengths to all the tumor voxels  because of patient surface changes and non‐rigid anatomic relationships. Until practical electronic, high‐resolution, morphing 3D detector arrays are available, we must continue to glean useful information from planar QA analyses.In the present study, we manually tracked and analyzed target detectors by pulling the related data out of the measurement files. For general clinical use, this approach would not be efficient and therefore is not acceptable. It is essential that the QA software analysis tools be able to import DICOM  radiation therapy structure sets from the treatment planning system and render structure projections for each beam. Then, analysis data filters could be designed to include only the detectors that correspond to beamlets that penetrate the defined structure for the beam. Geometric beam parameters, together with the beam isocenter relative to the structure coordinates, would therefore also be required and could be derived from the DICOM radiation therapy plan data.Z) motion as a unique function of superior–inferior (Y) motion. Therefore, it can uniquely indicate the phase of the respiratory motion cycle as described in TG‐76. However, in its current form, it cannot reproduce the actual patient trace from a surrogate marker in or on the patient anatomy. A future enhancement would be to enable the Z‐axis gating surrogate to be similarly motorized and programmed to match actual (or estimated or modeled) patient breathing traces. Additionally, it would be interesting to be able to program drifts and losses of correlation between the gating surrogate and the actual target (detector) motion. These variations would be possible with an independent motion device for the gating surrogate.This first implementation uses external markers that track anterior–posterior  was integrated and tested. It will be necessary to integrate other gating techniques such as the pressure sensor systemThe data acquisition was time‐efficient .The active detector size is small and therefore of high resolution.Absolute dose can be measured.The detectors are moveable and able to map accurately to motion kernel projections in the BEV.Integration with respiratory gating is possible.An existing, popular IMRT QA array is used for measurements.Existing and familiar methods of quantitative analysis are used.The 4D IMRT/SBRT QA prototype device meets the proposed requirements of a practical tool, namely:This device could be an integral part of a 4D IMRT/SBRT decision flowchart that incorporates target‐specific 4D motion kernels to assess dose degradation, to quantify interfractional variation resulting from interplay between delivery and target motion, to verify the respiratory gating technique, and even to determine the optimal duty cycle considering both dosimetry and delivery efficiency.The authors thank Virgil Willcut and Scott Brame for useful critique. This work was funded in part by Sun Nuclear Corporation  and Canis Lupus LLC .