Participatory mapping is a powerful methodology for working with community residents to examine social and environmental determinants of public health disparities. However, this empowering methodology has only been applied sparingly in public health research and practice, with limited examples in the literature. To address this literature gap, we 1) review participatory mapping approaches that may be applied to exploring place-based factors that affect community health, and 2) present a mixed-methods participatory geographic information systems (PGIS) examination of neighborhood assets  and challenges  related to access to public parks in South Los Angeles, California. By taking a participatory, fine-grained spatial approach to examining public park access with input from 40 South Los Angeles adolescent and adult residents, our community-engaged PGIS approach identified tobacco shops as previously unrecognized community institutions that are associated with increased neighborhood crime and violence. Our investigation revealed unique challenges in community-level public park access that would likely have been overlooked by conventional spatial epidemiology and social science methods, such as surveys and questionnaires. Furthermore, our granular community-informed approach supported resident and stakeholder advocacy efforts toward reducing the proliferation of tobacco shops through community organizing and policy change initiatives. We thus contend that it would benefit public health research and practice to further integrate empowering, grassroots-based participatory mapping approaches toward informing advocacy efforts and policies that promote health and well-being in disadvantaged communities. Systemic social and environmental inequities contribute to uneven health outcomes in disadvantaged communities. Participatory mapping is a powerful visual methodology for partnering with affected communities to develop grounded understandings of community health assets and challenges.We demonstrate use of participatory mapping as a potent methodology for diagnosing place-based determinants of health disparities, review participatory mapping approaches for public health research and practice, and present a case example of this methodology.Participatory mapping is ideally suited to diagnosing upstream determinants of health and prescribing downstream policy interventions that attend to resident interests and needs.Population health is fundamentally connected to the conditions in which people live, work, learn, and play . This phand social knowledge grounded in residents’ experience of place  providing an overview of participatory mapping approaches for public health and 2) illustrating the potential of participatory mapping by presenting a case example of community health asset and challenge mapping conducted as part of a Centers for Disease Control and Prevention (CDC) Racial and Ethnic Approaches to Community Health (REACH) project that was instrumental in diagnosing upstream determinants of health  and prescribing downstream policy-based interventions.Participatory mapping mirrors community-based participatory research and citizen science , with thHands-on mapping. An effective approach for working in low-resource settings is hands-on mapping, which has been applied to a range of health issues such as mapping arsenic exposure  to represent and explicate features of the social and built environment that affect public health. Methodologically, reference maps are particularly well suited to eliciting fine-grained spatial data, because they provide accurate geographical depictions of research sites that can easily be transferred to geospatial analysis platforms  to analyze community-identified interests from spatial epidemiology perspectives. This approach has been particularly effective in identifying community access to health services . With an emphasis on coproduction of knowledge found in community-based participatory research  and African American (31%) with inequitable access to public parks, a feature commonly associated with community health . Led by The Community Coalition, which has been organizing residents in South Los Angeles for health equity since 1990, established strategic partnerships to build research capacity and develop data-driven health promotion interventions. The Psychology Applied Research Center (PARC) at Loyola Marymount University provided research capacity, while St. John’s Well Child and Family Centers and To Help Everyone Health and Wellness Centers provided health care services. Partnerships with Advocates for Peace and Urban Unity, Reclaiming America’s Communities through Empowerment, and 3 Wins Fitness served to improve public park safety and recreational programming. Finally, the Los Angeles County Department of Public Health–Injury and Violence Prevention Program assisted with data acquisition.Public parks in South Los Angeles are often underused because of resident concern about nearby crime and safety issues . TherefoPublic park use tends to decline in high-crime areas . We seleTrained Community Coalition and PARC mapping facilitators and South Los Angeles residents convened at a local community center in March 2015 to map 1) resident walking routes to Helen Keller Park and 2) neighborhood characteristics  associated with park access. This information would then be scaled up to 3) examine place-based determinants of health across South Los Angeles, and based on these results, 4) develop grassroots solutions for improving recreational access.To achieve mapping objectives, as a collective group, residents were briefed on mapping procedures and informed that they could stop participating at any time. Participants then joined 1 of 4 contemporaneous, 1-hour mapping sessions, each with 8 to 12 participants. Two mapping sessions were organized according to resident location to account for geographic differences in resident experiences, a third session accommodated Spanish-language speakers, and a fourth session included community adolescents aged 15 to 18. In addition, public health officials and gang interventionists, who also possessed knowledge of the area, aided in session facilitation.Facilitators began each session by reviewing mapping objectives. Participants were then geographically oriented to recognizable neighborhood institutions on the 4-by-5-foot paper street maps  to confiThe mapping sessions revealed 5 assets and 14 challenges . Among tResidents contended that off-sale alcohol outlets compromised park accessibility and community mobility, asserting that these nuisance properties were magnets for crime and violence, a phenomenon that has been well documented in the literature . For exaResidents were also concerned about criminal activity around tobacco shops and, to a lesser extent, MMDs , with a young participant describing these properties as spaces that attract crime and violence. Although the literature at the time of our mapping project had noted property and violent crime associations with MMDs , crime-rTwenty-eight community residents reconvened 1 month after the initial participatory mapping sessions to review digitized PGIS maps . This foTo explore validity of this novel qualitative study on a community-wide scale, our South Los Angeles REACH team, including Community Coalition staff, conducted a cross-sectional PGIS investigation of the identified legal drug outlets’ geospatial associations with crime and violence in South Los Angeles. The team accordingly acquired and mapped the following point location data (from January through December 2014) across 116 contiguous census tracts in South Los Angeles: 1) all tobacco shops, off-sale alcohol outlets, MMDs, and grocery and convenience stores that sold alcohol and tobacco, and 2) property, violent, and total crime reported by the Los Angeles police and sheriff departments. We then examined mean rates of property, violent, and total crime within 100-, 200-, 300-, 500-, and 1000-foot spatial buffers of all properties and assessed geospatial associations between our 3 legal drug outlets and crime while controlling for pertinent demographic characteristics. This quantitative analysis, detailed elsewhere , was theLeveraging PGIS findings with PARC and Community Coalition–collected polling data indicating broad-scale resident concerns about crime and violence near tobacco shops , the ComThe case example presented here involved community residents and organizers, gang interventionists, public health and park officials, and health disparities researchers in collaboratively identifying research methods and procedures using the skills and expertise of our collective partnership. The resulting mixed-methods PGIS approach combined qualitative participatory mapping techniques involving reference maps with quantitative GIS analyses to connect resident spatial, contextual knowledge (primary data) with crime data (secondary data) to empirically confirm their experiences of place. These empirical data accordingly supported resident advocacy efforts that resulted in a major policy win that could limit proliferation of tobacco shops in Los Angeles County. We thus contend that participatory mapping is a powerful, visual mechanism of knowledge production for 1) diagnosing fundamental causes of health and disease, and 2) empowering disadvantaged communities to redress systemic inequities that manifest in health disparities through community organizing and policy change initiatives grounded in resident knowledge of place ,9.The empowering diagnostic approach of PGIS specifically — a unique approach to disparities research that blends qualitative participatory mapping with quantitative spatial analyses — is rooted in its ability to inform public health interventions such as community organizing and policy changes that listen to the voices of marginalized residents . In thisThe process of participatory mapping has its challenges, including significant time investments and fostering sustained resident participation. Additionally, participatory mapping generally depends on participant spatial literacy ,12. The Taking these strengths and challenges into account, we assert that public health research and practice would benefit from integrating and adapting empowering modes of participatory mapping to diagnose place-based determinants of health. When combined with technical GIS mapping procedures in the form of PGIS, for example, this participatory approach provides communities of practice with a bifurcated methodology for innovatively and rigorously investigating the problem of health disparities. Combining these participatory modes of spatial investigation can empower community residents and public health officials to affect the root causes of health disparities through community organizing and policy change initiatives that advance health and well-being in disadvantaged communities.


Global trends in cardiovascular disease (CVD) exhibit considerable interregional and interethnic differences, which in turn affect long-term CVD risk across diverse populations. An in-depth understanding of the interplay between ethnicity, socioeconomic status, and CVD risk factors and mortality in a contemporaneous population is crucial to informing health policy and resource allocation aimed at mitigating long-term CVD risk. Generating bespoke large-scale and reliable data with sufficient numbers of events is expensive and time-consuming but can be circumvented through utilization and linkage of data routinely collected in electronic health records (EHR).We aimed to characterize the burden of CVD risk factors across different ethnicities, age groups, and socioeconomic groups, and study CVD incidence and mortality by EHR linkage in London.The proposed study will initially be a cross-sectional observational study unfolding into prospective CVD ascertainment through longitudinal follow-up involving linked data. The government-funded National Health System (NHS) Health Check program provides an opportunity for the systematic collation of CVD risk factors on a large scale. NHS Health Check data on approximately 200,000 individuals will be extracted from consenting general practices across London that use the Egton Medical Information Systems (EMIS) EHR software. Data will be analyzed using appropriate statistical techniques to (1) determine the cross-sectional burden of CVD risk factors and their prospective association with CVD outcomes, (2) validate existing prediction tools in diverse populations, and (3) develop bespoke risk prediction tools across diverse ethnic groups.Enrollment began in January 2019 and is ongoing with initial results to be published mid-2021.There is an urgent need for more real-life population health studies based on analyses of routine health data available in EHRs. Findings from our study will help quantify, on a large scale, the contemporaneous burden of CVD risk factors by geography and ethnicity in a large multiethnic urban population. Such detailed understanding  of the burden of CVD risk and its determinants, including heredity, environment, diet, lifestyle, and socioeconomic factors, in a large population sample, will enable the development of tailored and dynamic (continuously learning from new data) risk prediction tools for diverse ethnic groups, and thereby enable the personalized provision of prevention strategies and care. We anticipate that this systematic approach of linking routinely collected data from EHRs to study CVD can be conducted in other settings as EHRs are being implemented worldwide.PRR1-10.2196/17548 Globally, cardiovascular disease (CVD) is a leading cause of disability and premature mortality, with the number of deaths attributable to CVD rising from 12.3 to 17.3 million between 1990 and 2013 . Thus, wIn England, the National Health Service (NHS) established a population-based Health Check program in 2009 to provide a systematic assessment and management of CVD risk for adults. Individuals aged 40-74 years without pre-existing CVD, diabetes, or hypertension are invited for a five-yearly check-up to identify and to receive advice and treatment for their risk of having a CVD event . CommissDietary exposures determine nutritional status, which may, in turn, impact CVD outcomes. As nutritional status is a key intermediary in the development of CVD, health services need to measure nutritional status as well as associated dietary exposures in order to guide appropriate preventative measures, particularly in multiethnic populations in primary care. The National Diet and Nutrition Survey (NDNS) and components of the National Survey of Health and Development (NSHD) have been developed to assess dietary exposure patterns, nutritional status, and associated social as well as biological factors within a sample of UK populations -19. HoweThe risk of CVD in an asymptomatic individual is based on risk factor data collected by their primary care physician to produce a numerical estimate. Traditional risk scores, such as those derived from the Framingham risk equation, have potential limitations, primarily because they were derived from a cohort of predominantly White individuals in the United States ,22. MoreFurthermore, QRISK prediction models contain imputations due to missing data. While established statistical methods are often used, considerations such as imputing cholesterol values to individuals without vascular disease could lead to weakened associations between cholesterol and CVD , as was These systems need to be interoperable to enable a systematic analysis of routine healthcare data collected in electronic health records (EHRs). However, over 100 commercial EHR vendors are operating within the NHS across primary, secondary, and tertiary sectors . While oWe developed the following study specific objectives:To robustly quantify and characterize, across diverse ethnic groups and sociodemographic groups, the burden of CVD risk factors among NHS Health Check attendees in a diverse population in London.To prospectively study the incidence of CVD within this population by EHR linkage.To validate existing CVD risk prediction algorithms and to develop novel, bespoke algorithms for CVD risk prediction among diverse multiethnic population groups.To characterize dietary exposures and nutritional status as well as their associations with CVD outcomes, using data from index assessment methods that mirror or correlate well with those used in national surveillance.We propose to conduct a large-scale, cross-sectional observational study of NHS Health Check attendees in London with additional virtual longitudinal follow-up established via electronic health record linkage of their primary  and secondary care  data over 10 years starting in 2009. One of the major providers of EHR software to GP practices is Egton Medical Information Systems (EMIS). GPs utilizing this EHR will be eligible to participate. GP practices using EMIS Web clinical systems across London will be invited to provide practice-wide consent to participating in the study by way of sharing pseudonymized data on individuals undergoing NHS Health Checks within their practices between 2009 and 2018. GP practices across London are being informed of the study and recruited through liaising with clinical research networks through information letters and Clinical Commissioning Group meetings. Data will be remotely extracted centrally by EMIS using Read codes.Our study, designed as a population-based registry at the outset, will collect, alongside NHS Health Check data, additional demographic variables and prescription information to help build a large and robust repository of primary care data on residents of London undergoing NHS Health Check from 2009 onwards in GP practices.All individuals seeking healthcare in the United Kingdom are assigned a unique identifier . This number allows the allocation of any subsequent data collected to the individual’s record and enables linkage with diverse data sources. For instance, the Office for National Statistics and Hospital Episode Statistics databases maintain records on mortality and clinical outcomes of individuals utilizing secondary healthcare services, respectively. Data from these sources can be linked through NHS numbers to the NHS Health Check data to provide a comprehensive and contemporary database on CVD risk factors (predictor variables) and outcomes across different ethnic groups. Other data sources recording clinical CVD outcomes such as the Myocardial Infarction National Audit Project and the National Institute of Cardiovascular Outcomes Research will also be harnessed to provide additional details relevant to this study.This process of data sharing and linking, while protecting an individual’s confidentiality, is possible due to pseudonymization and will be conducted by EMIS and a third party organization familiar with bespoke linkage. Using Open Pseudonymiser Software, EMIS will create a pseudonymized version of NHS numbers for individuals who meet the inclusion criteria. The data will be encrypted with a project-specific key. By using this encrypted key, an external organization will be able to link the NHS Health Check data with outcomes data through a similar pseudonymization process and a Global Unique Identifier (GUID). The research team will only have access to completely linked anonymized data as the linkage of NHS Health Check data with outcomes data will not contain the GUID.Although data are not available for 2009-2011, of the invited population for NHS Health Check in 2016-17, 51.6% and 49.9% were residing in London and the rest of England, respectively . In 2015To develop novel risk prediction tools for population groups, we anticipate that data will be available on approximately 200,000 individuals across London between 2011 and 2017. During 2009-13, of those with a recorded ethnic group, uptake of the NHS Health Check across England was greatest amongst South Asians (19.2%), Black Caribbeans (19.6%), Black Africans (15.7%), and Chinese (15.3%). Attendance was 16.9% in all other recorded ethnic groups and 17.4% in white Caucasians. Extrapolating the current rate of CVD incidence (2.4%) for people aged below 79 years in England on our estimated study sample of 200,000, we expect to encounter 15,000 CVD events giving 100% power to observe relative risks as modest as 1.2-1.5 . Within Cardiovascular risk factors (predictor variables) used to calculate QRISK2 include age, sex, ethnicity, index of multiple deprivations, smoking status, diabetes status, family history of CVD, chronic kidney disease (stage 4 or 5), atrial fibrillation, hypertension treatment, rheumatoid arthritis, lipids, blood pressure, and BMI. EMIS will also extract prescription data. CVD outcomes will include fatal and nonfatal coronary heart disease, fatal and nonfatal stroke, heart failure, all CVD-related hospitalizations (including those for revascularization), and all-cause mortality.Since the data for our study will be extracted at a single source (EMIS), this is likely to obviate the need for harmonizing, although we will undertake detailed quality checks (both at baseline and on follow-up) and undertake data cleaning, where necessary.By using appropriate statistical tests to perform univariate comparisons, the collected data will be initially analyzed to explore the cross-sectional characteristics of this population. Skewed data will be transformed to an approximately normal distribution, with the calculation of Pearson correlation coefficients and partial correlation coefficients for relevant factors of interest.Cross-sectional associations of baseline risk factors will be studied with adjustments for appropriate confounders using logistic regression analyses. Prospective associations between individual risk factors and CVD outcomes will be evaluated using Kaplan-Meier survival curves and further quantified by fitting Cox proportional hazards regression models with multivariable adjustments. Where possible, associations will be studied after making allowances for the time-varying effects of both exposures and potential confounders. Detailed analyses of the associations will be conducted in prespecified subgroups of participants . Established methods of calibration (Hosmer-Lemeshow), discrimination (C or D statistic), and reclassification  will be used to study the predictive ability of individual risk factors on CVD outcomes, with prespecified analyses involving multiple ethnic groups to enable direct, head-to-head comparisons of any differences.Additional analyses will be conducted to quantify the impact of factors such as access to healthcare and utilization rates , prescription rates and medication compliance, and patterns of healthy behavior on CVD risk . Standardized rates of prescription drug use will be calculated to investigate the extent of correlation between the present use of cardiovascular medication and cardiovascular risk. Variations in prescription patterns of CVD prevention and risk factor control, discontinuation of prescribed medication(s), and adverse effects to prescription medications from various therapeutic categories such as anti-hypertensive agents, lipid-lowering drugs (statins), and antidiabetic medication will be further assessed for their impact on CVD as time-dependent covariates in Cox regression models. Physical measurements within the NHS Health Check program will be obtained by the GP practices according to standard operating procedures, anticipating minimum inter-observer variability. Analyses to explore potential sources of heterogeneity concerning physical measurements (besides other characteristics) will also be conducted.New and existing risk prediction models will be compared in terms of their ability to predict the onset of CVD across diverse population groups to develop improved risk prediction tools for primary prevention of CVD using outcomes data up to 2020. The resulting CVD risk algorithm will be calibrated by further analyses of CVD outcomes data of these patients through to 2027.The study is ongoing with enrollment underway since January 2019. Recruitment ended in January 2020, with extraction and linkage completed by March 2020. We expect the initial results for NHS Checks conducted between 2009 and 2018 and linked to Hospital Episode Statistics and Office for National Statistics to be published in mid-2021. This research has been supported by an unrestricted investigator-initiated research grant from Regeneron Pharmaceuticals to Imperial College London in 2015.The study protocol underwent an external peer review before the ethics submission. This study has received a favorable ethics opinion by the East Scotland Research Ethics Committee (Ref: 17-ES-0104), Health Research Authority, and adopted by the clinical research network portfolio in November 2018.Nationally delivered, the NHS Health Check program has the potential for universal outreach in the United Kingdom. However, differences in uptake of this program may lead to inadvertent and undesirable health inequalities . However, it is unclear whether (and to what extent) ethnic differences at a population level drive such disparities, and whether targeting specific sociodemographic subgroups within the population might help mitigate CVD risk.The complex interplay and variations of individual risk factors with wider determinants between and within regions and population groups reinforce the need for a detailed understanding of different cultural, socioeconomic, and epidemiological contexts for developing tailored population strategies.Given its ethnic diversity , London provides the ideal backdrop for studying CVD risk factor burden in all the permutations mentioned above. It has been estimated that the proportion of BME groups in London is 41% (10% in the rest of England). Moreover, a report commissioned by the King’s Fund found greater health inequalities in London than in the rest of England . For insThus, the aim of our study, using NHS Health Check data in London, is to understand the burden of CVD risk factors and to eventually validate/develop ethnic-specific CVD risk prediction tools to inform public health policy and guidelines which could lead to improvements in overall health outcomes and reduction in healthcare costs.Ethnic diversity in England in general, and London in particular, has hitherto not been systematically captured in large-scale studies creating uncertainty in the existing guidelines on CVD risk prevention. QRISK2 score has been shown to underpredict CVD risk in population groups such as South Asians, in part reflecting low representation of the ethnic groups in the cohorts to derive sufficient information to inform risk prediction tools adequately ,41. ThisMoreover, the data from this study could help develop bespoke risk prediction models across diverse ethnic groups that can be embedded into the existing GP EHR systems. Following the development of such models, individuals of diverse ethnicities could potentially be reclassified into higher- or lower-than-predicted CVD risk categories, thereby enabling more tailored approaches to prevention or intervention. By contrast, if conventional risk factors were found not to be associated with discernible differences in CVD risk across various ethnic groups, then our findings will have the potential to influence future research aimed at addressing alternative (and hitherto unexplored) risk factors (such as genetic variation or dietary factors) contributing to excess CVD risk in ethnic minorities. Further offshoots from the TOGETHER research program will not only be able to address some of the novel hypotheses regarding ethnic variation in CVD risk but also serve as a platform for pragmatic randomized controlled trials to explore, for example, various emerging health technologies. One such approach could be leveraging the use of mobile phones/smartphones and applications (apps) to modify risk factors  and thenAs CVD burden varies between population groups and by regions, our study has the potential to investigate the expression of this disease and the contemporary risk factors in a large multiethnic cohort. Thus, our research can be considered a contemporary Framingham study on a large scale. Combining a real-life observational approach with the potential for yearly updates from the EHRs will offer new insights and understanding of the burden of risk factors for re-calibration of the variables used to derive risk prediction tools and dynamic improvement of risk prediction algorithms. Longitudinal follow-up will help quantify the incidence of CVD and, therefore, the derivation of population attributable risk (PAR) . The abiThe proposed analyses are in keeping with statistical analyses conducted in other similar large-scale population-based studies -47. As tDespite the development of evidence-based guidelines and tools by the NHS, opportunities to reduce CVD mortality and morbidity are still being missed. Premature mortality and high healthcare costs associated with CVD underscore the need for a more detailed investigation into CVD risk across multiple ethnic groups since residual CVD risk remains a major challenge for health systems around the world. With the identification of more than 200 risk factors , determi


Immunoglobulin light chain (AL) amyloidosis is a rare, multi-systemic disorder characterized by two disease processes: an underlying plasma cell dyscrasia that provides the source of pathologic light chains, and the resulting organ dysfunction caused by deposition of amyloid light chain fibrils. There are no FDA approved treatments for AL amyloidosis; regimens developed for multiple myeloma are used off-label to treat the plasma cell disorder and no therapies are directed at organ deposition. Thus, an unmet medical need persists despite advances in disease management. A public-private partnership was recently formed between the Amyloidosis Research Consortium (ARC) and the US Food and Drug Administration (FDA) to bridge scientific gaps in drug development for the treatment of AL amyloidosis.The inaugural Amyloidosis Forum was convened at FDA on 12 November 2019 and led by a multidisciplinary panel of physicians, health outcomes professionals, and representatives from the FDA, ARC, and pharmaceutical companies. Patients provided important perspectives on the pathway to diagnosis, challenges of rigorous treatment, and the burden of disease. The panel reviewed the epidemiology, pathobiology, and clinical features of AL amyloidosis. Hematologic characteristics, staging systems, and response criteria were examined with clear consensus that a “deep response” to plasma cell-directed treatments was critical to overall survival. Emphasis was placed on the heterogeneous clinical phenotypes of AL amyloidosis, including cardiovascular, renal, neurological, and gastrointestinal system manifestations that contribute to morbidity and/or mortality, but render challenges to clinical trial endpoint selection. FDA representatives discussed regulatory perspectives regarding demonstration of clinical benefits of investigational therapies in the context of a rare disease with multi-systemic manifestations. The panel also highlighted the potential importance of well-designed health-related quality of life instruments, quantification of system organ effects, the potential of advanced imaging technologies, and survival prediction models.The Amyloidosis Forum identified a clear need for novel trial designs that are scientifically rigorous, feasible, and incorporate clinically meaningful endpoints based on an understanding of the natural history of the disease in an evolving therapeutic landscape. Future forums will delve into these issues and seek to include participation from additional stakeholders. Immunoglobulin light chain (AL) amyloidosis (ORPHA:85443) is a rare disease caused by a monoclonal plasma cell disorder and characterized by the aggregation and deposition of insoluble amyloid fibrils derived from misfolding of monoclonal immunoglobulin light chains (LC). Despite its rarity, AL amyloidosis is the most commonly diagnosed systemic amyloidosis with an estimated prevalence of 1–5 per 10,000 , 3. AL awww.arci.org) and the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER). The goal of this PPP is to identify and bridge the scientific gaps that are acting as barriers to drug discovery and development for the treatment of AL amyloidosis. The PPP seeks to leverage expertise and resources of all stakeholders  for the conduct of mutually beneficial scientific activities in the precompetitive domain to support bringing new, safe and efficacious therapies to patients with AL amyloidosis  is a cooperative arrangement between two or more public and private sectors, typically of a long-term nature. In 2019, a PPP was formed between the nonprofit Amyloidosis Research Consortium , educate PPP participants on issues CDER reviewers are likely to consider important for precompetitive projects under development, and explain why certain issues may have importance to the CDER regulatory community. The CDER PPP liaison may arrange to bring other FDA staff into the discussion if needed. Importantly, CDER staff participation will not be related to any specific regulatory application, product, or other non-public information. Project results generated by this PPP will be made broadly available to the public to benefit public health.This review summarizes proceedings of the first of an anticipated series of meetings convened at FDA on November 12, 2019. The inaugural Amyloidosis Forum focused on achieving a broad understanding of AL amyloidosis. The forum consisted of a series of presentations and panel discussions. The panel was comprised of 11 physicians from medical institutions in the US and Europe, 2 health outcomes professionals, representatives of ARC, 3 pharmaceutical companies, and 6 divisions of the FDA. Patients provided important perspectives on the path to diagnosis, challenges of rigorous treatment, and the burden of disease. The panel reviewed the epidemiology, pathobiology, and clinical features of AL amyloidosis. Hematological characteristics, staging systems, and response criteria were examined, and a clear consensus emerged that a “deep response” to plasma cell clone directed treatments was critical to OS. Emphasis was placed on the heterogeneous clinical phenotypes of AL amyloidosis, exemplified by varying impacts on the cardiovascular, renal, neurological, and gastrointestinal systems that all substantially affect morbidity. The heterogeneous presentations and disease courses make selection of endpoints for interventional clinical trials particularly challenging. FDA representatives discussed regulatory perspectives in the context of rare diseases and clinical outcomes assessments. The panel also highlighted the importance of patient-reported outcomes (PROs), the potential of imaging biomarkers to guide dose-selection, and the use of survival prediction models to guide trial length. The Amyloidosis Forum identified a clear need to identify, develop, and/or modify novel trial designs and clinical endpoints to encourage drug development in this rare disease. The availability of natural history data is crucially important to meet these needs.AL amyloidosis is sometimes termed a “great imitator disease.” Establishing an early and accurate diagnosis of amyloidosis was viewed as a significant challenge based on results of a global survey conducted in patients, family members, and caregivers . PresentSystemic AL amyloidosis is a monoclonal plasma cell disorder. More than 90% of patients have an abnormal serum free light chain ratio . There aNearly all organs can be affected in systemic AL amyloidosis resulting in a myriad of clinical features; a majority of patients have involvement in one or two organs, with the heart (76%) and kidney 53%) being the most commonly impacted Fig. b. Approx3% being To highlight the multi-systemic aspects of AL amyloidosis, the Forum panel included hematologist/oncologists, physicians who specialize in the treatment of the cardiac, renal, gastrointestinal, and neurological manifestations of the disease, and representatives from corresponding divisions of the FDA. The panel discussed specific comorbidities and challenges with cardiac, renal, gastrointestinal, and neurological involvement. Specifically, AL amyloidosis patients with kidney involvement are often asymptomatic; generally presenting with an abnormal glomerular filtration rate  and/or proteinuria (75%). Gastrointestinal involvement generally results in decreased absorption, depending on whether amyloid fibrils deposit in the mucosa or muscle/nerve. The most common gastrointestinal symptoms in AL amyloidosis are early satiety, weight loss, and constipation/diarrhea; all of which have a large impact on health-related quality of life (HRQOL). In patients with gastrointestinal involvement, signs and symptoms could potentially be collected directly from patients using a fit-for-purpose PRO instrument(s) to obtain a clinically meaningful measure of treatment benefit; however, these symptoms are often confounded by adverse drug effects and currently there is no fit-for-purpose AL amyloidosis-specific PRO instrument. The FDA encourages early discussion between sponsors and the review division on how to measure clinically relevant endpoints. Neurological involvement in AL amyloidosis may be autonomic  and/or somatic . Composite neurological scores that incorporate the clinical, electrophysiological and autonomic attributes assessed by trained personnel are considered an appropriate measure of treatment response/regression.Challenges for treating cardiac symptoms and assessing treatment response were also discussed by the panel. Many standard treatments for congestive heart failure  are either contraindicated or poorly tolerated at high doses in patients with AL amyloidosis. Discussion focused on the potential of emerging echocardiographic, magnetic resonance imaging (MRI), and nuclear/PET imaging techniques for providing objective measures of cardiac involvement and potentially standardized metrics for cardiac responses to therapies being evaluated in multicenter clinical trials. Imaging technology was identified as an area for further review by the Forum.There has been an evolution of AL amyloidosis staging systems based on variables independently prognostic for OS. Disease staging is driven by factors influencing prognosis (i.e. extent of cardiac and/or other organ involvement), and the “tumor” burden/characteristics. In AL amyloidosis, response assessment includes both hematologic response and involved organ response. Published literature suggests a correlation between the depth of hematologic response and improved OS , 15–19. Although there are no FDA approved therapies for the treatment of AL amyloidosis, treatment modalities for AL amyloidosis tend to follow multiple myeloma treatment paradigms. High-dose melphalan followed by autologous stem cell transplant (HDM-SCT) is among the most effective cytotoxic therapies against plasma cells and leads to reduced production of the abnormal LC and prolonged survival. However only 25–35% of patients with AL amyloidosis are eligible for HDM-SCT because of poor functional status, advanced cardiac involvement, advanced renal dysfunction, low blood pressure due to autonomic neuropathy, or age , 25. NonPredictors of organ response include the severity of organ dysfunction at diagnosis, time to treatment, plasma cell burden, and the depth of hematological response. The number of organs with a response following treatment  correlates with OS . The depThe kinetics of hematologic and organ responses are distinctly different, with organ responses being delayed following hematologic response. Initial organ responses are observed at 6–9 months post treatment initiation with maximal responses observed between 24 and 36 months post treatment initiation  clearance is dependent on renal function.The development of composite response criteria that address both the hematologic and organ responses may provide a new outcome measure to assess both the underlying plasma cell dyscrasia and the resulting organ damage inherent to AL amyloidosis. A proposed composite index would rank established hematologic criteria and separately rank organ response. Initial analysis conducted on two separate cohorts demonstrated a significant difference in survival probability between two groups based on composite scores; results were reproduced in both cohorts Fig.  10]. Va. Va10]. Overall, patient prognosis is dependent on many factors: the extent of cardiac involvement and/or other organ involvement, “tumor” burden, the depth of hematologic response and organ response. For patients with AL amyloidosis, the extent of cardiac involvement drives OS and presents the greatest unmet medical need.During the Forum, three patients shared their stories and highlighted the varying degree to which AL amyloidosis is a multi-systemic disease posing numerous challenges. Patients provided important perspectives on the path to diagnosis, challenges of rigorous treatment, and the burden of disease. These important testimonials shared commonality: AL amyloidosis and current treatment both significantly and broadly impact HRQOL. Treatment has a major impact on HRQOL because the rigorous therapeutic regimens are difficult for patients to tolerate. Published reports and qualitative interviews with physicians and patients have further characterized the burden of disease in AL amyloidosis , 29–31.A conceptual model of AL amyloidosis was developed to depict the impact of disease, treatment, and relationships among the impacts . The conn = 341) and clinic-based (n = 1438) observational studies [Several PRO instruments have been utilized as outcome measures in AL amyloidosis studies, including organ-specific measures , health utility scores , and generic measures of health status . One of the health status measures discussed at the Forum was the SF-36, a PRO instrument that has been widely used in clinical studies . The psy studies .N = 544), patients with AL amyloidosis averaged a baseline physical component summary (PCS) score of 35; significantly lower than age-matched population norms ; Neurology Products, the Rare Diseases Program, and Clinical Outcomes Assessments Staff each provided perspectives on the Agency’s approach to multi-systemic diseases. The breadth of engagement and involvement across several divisions provided a unique opportunity for attendees and panel members. The representatives all recognized the importance and challenge of drug development for rare, heterogeneous diseases such as AL amyloidosis and emphasized the need for a collaborative, multi-disciplinary approach to drug development. Engagement of regulatory agencies by both industry and patient advocacy groups was encouraged “early and often,” beginning as early as the nonclinical development phase.The FDA discussed both traditional and accelerated approval pathways and considerations for choosing appropriate primary endpoints. In the traditional approval pathway, substantial evidence of efficacy can be established by demonstration of improvement of a clinically meaningful endpoint  or a validated surrogate endpoint . Approval requires successful conduct of two adequate and well-controlled trials. In special circumstances, when it is highly impracticable to conduct two trials, the successful conduct of one adequate and well-controlled trial with confirmatory evidence  may be sufficient to support approval.Several expedited programs may help accelerate drug approval for rare diseases that are serious and life-threatening. The accelerated approval program is a pathway to marketing approval for a new drug product on the basis of adequate and well-controlled clinical trials that establish an effect on a surrogate or intermediate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict a meaningful clinical benefit over existing treatments on the life-threatening or severely debilitating aspects of the condition. Post-marketing confirmatory trials may be required to verify and describe the anticipated effect. The FDA panelists highlighted the difficulties with use of biomarkers that are presumed to be surrogates, citing the variability of NT-proBNP changes from baseline with mortality outcomes in clinical trials, the experience with ventricular arrhythmia suppression in the CAST trial, and the increased mortality that has been seen with cardiac inotropes in spite of short term hemodynamic improvements. Published evidence in AL amyloidosis suggests NT-proBNP levels are associated with cardiac function and OS in AL amyloidosis , 37. It https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical).The feasibility of a particular endpoint is dependent on an understanding of the natural history of disease progression, mechanism of action of the drug, and the ability to identify the population in which the treatment benefit can be detected. Specific challenges were acknowledged for investigating AL amyloidosis, including the heterogeneity of the disease , the need for tailored statistical approaches and focused trial populations, and the process for development of novel clinical outcomes to measure and predict responses. Given the limited populations available for study of rare diseases and the importance of patient-focused drug development, the FDA has issued a series of guidance documents intended to assist pharmaceutical companies and patient groups in the design of trials with clinical outcomes that reflect the patient voice and clinical benefit, and that are sensitive enough to detect meaningful changes . When considering a multiple endpoint concept, careful consideration should be given to identifying the endpoint components (and the magnitude of the changes of those components) that would represent clinically meaningful effects.Discussion among panelists highlighted these and several other challenges to drug development for AL amyloidosis, including delays to drug development while conducting prospective natural history studies, reliance on retrospective data in a changing anti-plasma cell treatment landscape, and assumptions that efficacy and/or safety in one organ system can be extrapolated to all other organ systems. While the Agency representatives acknowledged limited experience with composite endpoints and hierarchical ranked sum analyses that include components spanning cardiovascular, renal, neurological, gastrointestinal, and hematologic organ systems, a multiple endpoint concept may be helpful for heterogeneous diseases such as AL amyloidosis  or the downstream effect . Selection of trial endpoints must therefore consider the drug’s intended mechanism of action. Chemotherapy, HDM-SCT, immunotherapy and other investigational agents that target the underlying clonal disorder should assess the hematological response. Therapeutic approaches targeting amyloid deposition and organ function  should assess organ response(s)  and ensure there is no worsening of clinical outcomes. Currently, only anti-plasma cell therapies have demonstrated clinical benefit and there remains much to learn about assessment of “anti-amyloid” treatments Fig. .Fig. 6CObjective endpoints of OS and hematologic responses are primary endpoints with clear clinical benefit. However, depending on the disease severity of the studied population, OS response analyses may require trials of extended duration, obligating patients and resources that might be better used for the development of a different therapy. Potential pharmacodynamic endpoints for phase 2 studies could include laboratory and/or imaging biomarkers, although many  biomarkers have limitations for regulatory acceptance as primary endpoints in phase 3 trials. There was consensus on the need to capture symptom responses inherent to AL amyloidosis and the development of fit-for-purpose PROs Fig. . FunctioGiven the heterogeneity of the disease, trial populations may be subgrouped by organ involvement. The extent of cardiac involvement has a large impact on OS and therefore represents a patient population with unmet medical need and a clear objective primary endpoint for interventional trials. For advanced patients with severe cardiac involvement (Mayo Stage IIIb), improvement in OS is an achievable endpoint. However, for this severely affected cardiac population, anti-plasma cell treatment may not directly lead to end organ improvement; therefore high mortality due to disease progression should be anticipated by Institutional Review Boards/Independent Ethics Committees, sponsors, and regulators. There also may be difficulty in distinguishing toxicity due to investigational product from symptoms of disease. Endpoint selection in patients with early (Mayo Stage II) and moderate (Mayo Stage IIIa) cardiac involvement are more challenging.Patients with renal involvement have a high risk of progression to ESRD; it may be possible to design a composite endpoint based on eGFR, proteinuria, and the need for renal replacement therapy to detect a benefit in this population . If patiSelection of an appropriate study population is paramount to successful trial design; however, AL amyloidosis trials present several limitations. Eligibility criteria that are too selective may restrict the population of an already rare, heterogeneous disease and pose challenges for enrollment and subsequent development of treatments to benefit all AL amyloidosis patients. Unnecessarily restrictive eligibility criteria may also limit safety data in important subgroups, such as those with renal involvement and reduced kidney function.While there are challenges in designing trials with newly diagnosed patients, the study of patients with relapsed/refractory AL amyloidosis presents additional challenges. Established response criteria, median OS, cardiac and renal response/progression criteria were all defined using reference data from the first-line therapy setting , 37 and A recent study indicated 35% of patients (92/259) who responded to first-line therapy required second-line treatment after a median of 49 months; of the 92 patients, 48% did not have “measurable disease” . PatientThe panel further highlighted an inherent disconnect between the speed of clinical trial enrollment and the need to provide relapsed/refractory patients access to clinical trials. Physicians are also hesitant to wait to treat patients until stringent criteria for relapse are met; an issue further confounded by the delayed kinetics of organ response to first line therapy. The panel discussed whether a VGPR is “good enough” or whether additional lines of therapy should be introduced sooner given that the balance of FLC and organ deposition is still poorly understood. Overall, the current climate does not provide incentive for sponsors to design salvage trials since they often take years to accrue patients and demonstration of improved OS may not be easily achieved. At the same time, symptom scores and HRQOL PROs are likely not robust enough or applicable in the relapsed/refractory setting. Potentially, development of a composite or multi-domain responder index may be helpful for drug development in the relapsed/refractory setting provided it can be developed based on robust understanding of natural history and available Phase 1/2 data.The inaugural Amyloidosis Forum provided a basic disease primer and identified challenges and opportunities in the development of new treatments to decrease the mortality, improve function, and/or improve HRQOL in patients with AL amyloidosis. The Forum identified a clear need for novel trial designs and clinical endpoints to address the burden of disease and therapeutic effects, the development of which necessitates natural history data in an evolving therapeutic landscape. Development of PROs tailored to symptomatic burden and HRQOL in AL amyloidosis may be required to provide specificity of therapeutic effect and inform mechanism of action and to measure burden of illness during therapy. Qualification of robust and reproducible imaging techniques may provide objective clinical outcomes to assess burden of disease and response to therapy. Future forums will delve into these issues and seek to include participation from additional stakeholders. The PPP is envisioned to serve as a model approach to address challenges in precompetitive drug development for other rare diseases.


Emerging technologies have driven the rise of many water-related startups and created new opportunities in water markets. The global water crisis could be mitigated by applying innovative technologies, sound water management decisions, and successful business models, and it is essential to better understand the status and future trends of emerging water markets. This study aims to discover shifts in the entrepreneurial landscape and evaluate water startups' development performance for the sustainable development of emerging water markets. We collected and analyzed data including the founding date, service area, service provided, details of funding raised, revenues, and consumer responses on 132 water startups founded between 2008 and 2018 in California, USA. Our results indicated that municipal area dominated the emerging water startup market compared to agricultural and industrial areas, and that many of the services provided shifted from conventional technologies to digital technologies. Though digital water startups' current revenues were relatively low, digital techniques applied in the water industry exhibited the good potential to promote public health and water saving. The development trends and performance of water startups enlighten the technological and commercial revolutions in the emerging water market, and provide guidelines for the decision-making in relevant stakeholders in the scientific, governmental, and industrial communities. As the However, the fact that digital startups occupied the second place in the mean and median values of CB Rank  demonstrPhysical/chemical/biological technology ranked medium in the mean value and median value of the total funding amount  and CB RTo study consumer response, we evaluated the mean values of average monthly visits to sites . Furthermore, monthly page views per visit, bounce rate, and visit duration per visit (accessed from Crunchbase in February 2019). Detailed results were listed as The preliminary analysis showed that digital technology exhibited high promise and long-term development trends. Further investigation was done on the capital, revenues, and consumer responses of digital technology. The primary customer of digital water startups was municipal/household area (45.26% of the customers), followed by agricultural and industrial areas . The digWe evaluated the same indicators for the consumer response to digital water companies as that for all water startups , includiPopulation growth and urbanization are common factors intensifying water demand in many cities, but different cities have specific water problems based on other local situations. For example, high agricultural water usage and recent local wildfires in California increased water demand, while the main problem facing industrial cities around the Liao River Delta in China is water pollution . Thus, pNotably, due to the data availability, some results may not be representative, for example, there were only 1–3 data points for the total capital funding and revenue in consulting, NGO, and design categories. Another major limitation lies on the limited sample size and short duration of available data to evaluate the consumer response, though web page visits may not necessarily result in actual customer relationships. A better way to evaluate consumers’ feedback is to conduct customer surveys, which should be investigated in future studies. Nevertheless, the main conclusions of current study are sound with concrete support of the presented data and analysis.In this study, we investigated the shifting landscape and development performance of emerging water startups in California. With population growth, urbanization, and improvements in living standards, most water startups chose to serve municipal/household areas. Agriculture was the second-largest target market for water startups due to California’s agricultural characteristics. An increasing fraction of the services provided were changing from conventional technologies to digital technologies. Investors were more interested in investing in digital water startups than in other services, but not all digital startups can get large amounts of funding. Although digital startups had the lowest mean total revenue, they could yield overall social benefits by decreasing water bills, increasing public awareness of water use, and protecting public health. Conventional physical/chemical/biological technologies were still crucial in emerging water markets, with higher revenues than other services, but the number of startups in this sector decreased. Consulting and VC/financing/incubator/accelerator were more popular with consumers than other services. These findings shed light on current water market conditions in California, and can be used to guide entrepreneurs, scientists, policymakers, and venture capitalists. Entrepreneurs and scientists would have better scenes of the technologies and service demand from the water markets, while the venture capitalists would improve the investment strategies based on the current overall performance of water startups. It also provides a solid reference for policymakers to formulate relevant measures and provide financial support to promote the sustainable development of emerging water markets.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.S1 Dataset(XLSX)Click here for additional data file.S1 Text(DOC)Click here for additional data file.S2 Text(DOC)Click here for additional data file.S3 Text(DOC)Click here for additional data file.


This Special Issue on geriatric care models features 18 papers highlighting the evolving nature of healthcare delivery and the leadership and quality enhancement research provided by geriatric care models [Home-based primary care is embraced by health systems that reward value over volume and target the most complex patients, providing services such as hospital at home, and improving the quality of life for home-limited patients and their caregivers .Innovative programs to care for frail older adults in the community include the Case–Finding for Complex Chronic Conditions in Seniors 75+ Program—a proactive approach to identify frail elderly people at highest risk of poor outcomes that targets multidisciplinary interventions to maintain health and well-being . GeriatrThe Emergency Department (ED) is uniquely positioned to improve the care of older adults. A dedicated Geriatric ED can replicate an Acute Care for Elders model of interdisciplinary care to provide comprehensive care plans for vulnerable older adults at risk of morbidity, ED revisits, and potentially avoidable hospital admissions .Nursing home residents can receive access to specialty care delivered to nursing homes using video visit technology, as demonstrated by the Vet Connect Program . Active Suboptimal care transitions increase the risk of adverse events and result from poor care coordination among providers and healthcare facilities. Facilitation of a smooth and seamless transition relies on the abilities of skilled nursing facilities (SNFs) and primary care teams, as well as community agencies, to coordinate together in a patient-centered manner . GeriatrAcute Care for Elders (ACE) Units show increased adherence to evidence-based geriatric processes, improve patient functional status at the time of hospital discharge, and reduce the length of stay and costs for older adults ,14,15. IComprehensive geriatric assessment has become a fundamental part of clinical geriatric care. Geriatric evaluation and management have evolved and are now occurring in long-term care, homes, and outpatient settings . Availab


Gso ba rig pa), translated as the “knowledge field of healing.” Sowa Rigpa is a scholarly Asian traditional medical system rigorously transmitted through canonical texts and oral teachings originating in Tibet with an extensive pharmacopeia, comprehensive treatment repertoire, and nuanced etiological explications of its nosology of diseases. This medical tradition is practiced across a broad region of Asia, particularly in Tibetan regions of China, Himalayan regions of India , Nepal, Bhutan, Mongolia, Russia, and recently in Europe and North America. The data herein depicts disease classifications listed in the encyclopedic compendium “Oral Instructions Treatise” (Man ngag rgyud) of the Tibetan medical classic, the Four Medical Treatises (Rgyud bzhi), compiled in written form during the twelfth century CE. Visualized examples depict etiological relations among diseases in five of the fifteen major categories of disease: rLung Illnesses, Béken Illneses, Pediatric Conditions, Eye Conditions and Tropical Infectious Diseases. Disease names were entered into spreadsheet format and categorized by etiological hierarchical structure. Data are written in Unicode Tibetan font to retain fidelity to entries in the classical text, with parallel columns in standard Wylie transliteration. Subsets of the data are visually depicted through a graphic platform called Interactive Tree of Life to demonstrate etiological associations. This dataset is the first publicly available enumeration of the specific diseases, classifications and etiological relationships from the Tibetan medical classic. The data are linked to the article entitled “Tibetan Medical Informatics: An Emerging Field in Sowa Rigpa Pharmacological & Clinical Research” .This article shares the comprehensive dataset and five visualized examples of disease categories in Tibetan medicine, or Sowa Rigpa (Tib.  Co-authors categorized the data vis-à-vis analytics of their etiologic relationship and classification hierarchy (Gso ba rig pa) translated as the “knowledge field of healing,” which is a scholarly Asian traditional medical system rigorously transmitted through canonical texts and oral teachings that originated in Tibet in the eighth century and transmitted across the Himalayas to greater central Asia. This medical tradition is practiced today in Tibetan regions of China, Himalayan regions of India , Nepal, Bhutan, Mongolia, Russia, and recently in Europe and North America. Compiled in the twelfth century CE, the Four Medical Treatises provides the foundational canon for the Sowa Rigpa tradition. Graphically representing this data has facilitated researchers in assessing distinctions across enumerations [Four Medical Treatises’ compendiums as well. Clinical diagnostic data can now map onto the theoretical categories to determine what illness types are implemented in diagnostic practice and to what frequency [These data  and type (rigs) enumerations are listed separately. For example, in the rLung (rlung) illness category, a class of disorders likened to neuroendocrine conditions [rlung, heart rlung, lung rlung, liver rlung, stomach rlung, colon rlung, and kidney rlung. These classifications were entered into the spreadsheet separately and placed in their respective hierarchies of etiology and disease category. Such diseases can be re-analyzed according to other specific etiologic or classification relationships as well. Raw data are written in Unicode Tibetan font to retain fidelity to entries in the classical text, with parallel columns in standard Wylie transliteration [Data were extracted by textual analysis and entered into spreadsheet form as raw list , and accnditions , there ateration . VisualiInteractive Tree of Life (itol.embl.de). This platform was designed by its developers to facilitate the display, manipulation and annotation of phylogenetic trees. Because of the traditional use of allegorical trees in Tibetan medicine to display relationships across divisions, categories and classes, such as disease etiologies and nosologies, this tool provides an ideal mode to visualize the data presented herein. Use of this tool facilitates graphical depictions of the existing illnesses in a given disease category and their respective hierarchies as detailed in the Four Medical Treatises. Note that categories in the hierarchy, such as “location” and “type,” are drawn with separate lines in the graphical depiction as well but are not counted as separate illnesses. Only the final subcategories are enumerated as separate illnesses. Graphical methods aid analyses of illness classifications in the Four Medical Treatises as indicated above.To create the graphic visualizations, subsets of the data were converted to.txt files and uploaded to the data visualization platform This dataset also allows for greater data manipulation power in, for example, collapsing disease category by location and looking at specific etiologic characteristics that might have similar relationships. For example, the class of diseases related to the biomedical concept of cancer all stem from etiologic relationships to interstitial fluid and poor blood quality . MergingThe above figures are visualized depictions of subsets of five of the fifteen categories of disease classifications and etiological relationships from the Tibetan medical classic. The accompanying raw data provides the comprehensive list of diseases and associations.


The endocannabinoid system (ECS) is a lipid cell signaling system involved in the physiology and homeostasis of the brain and peripheral tissues. Synaptic plasticity, neuroendocrine functions, reproduction, and immune response among others all require the activity of functional ECS, with the onset of disease in case of ECS impairment. Estrogens, classically considered as female steroid hormones, regulate growth, differentiation, and many other functions in a broad range of target tissues and both sexes through the activation of nuclear and membrane estrogen receptors (ERs), which leads to genomic and non-genomic cell responses. Since ECS function overlaps or integrates with many other cell signaling systems, this review aims at updating the knowledge about the possible crosstalk between ECS and estrogen system (ES) at both central and peripheral level, with focuses on the central nervous system, reproduction, and cancer. Cannabis sativa plant since some phytocannabinoids, including the main psychoactive principle Δ9—tetrahydrocannabinol (Δ9-THC), can mimic the effects of endocannabinoids by binding to their endogenous receptors    with a pe (OEA)] .As for BPA, in the same animal models also the plasticizer DiNP had a similar effect on endocannabinoid tone and FAAH activity , with coLow BPA doses  modulate the ECS components in exposed mouse primary Sertoli cells in parallel to an increase in inhibin B levels; in this system, the BPA dependent effects on inhibin B are further enhanced by the blockade of either CB2 or TRPV1 receptors  revealinRecently the effects of BPA on ECS have been evaluated in pregnant women, providing evidence of BPA interference in ECS signaling and hypothesizing that BPA may induce adverse pregnancy outcomes modulating the activity of the ECS . In this9-THC), used as an indicator of cannabis consumption, in n = 15 individuals has been linked to lower concentrations of endocannabinoids in semen and low circulating AEA in blood, suggesting a possible Δ9-THC-mediated negative feedback on AEA production and concentration; by contrast, no correlation was observed between the presence of urinary bisphenols and endocannabinoids [ECD exposure has been suggested to be a possible cause of the decline in human semen quality observed in the last few decades ,183, witabinoids .Taken together, the world’s widespread distribution of EDCs points out a concrete risk for reproductive health and ECS may represent a target for disease, but also a biochemical marker for the toxicological screening of exposed subjects.Cardiovascular diseases are the leading cause of death in postmenopausal women in developed countries, suggesting that estrogen deficiency may play a causative role . A positAlso, human T lymphocytes witness an intimate cross-talk between steroid hormones and ECS, with critical implications for human reproduction . In circThe ECS is present in both central and peripheral organs and several findings suggest that endocannabinoids levels, ECS degrading enzyme activity as well as CB1 and CB2 receptor expressions are altered in sex-hormone dependent malignant tissues  as summaCNR1 gene encoding for the CB1 receptor [9-THC and cannabidiol, CBD) and endocannabinoids like AEA inhibited cancer cell growth and metastasis formation both in vitro and in vivo reviewed in [CNR1 gene promoter [9-THC did not cause any effect [In hepatocellular carcinoma, CB1 and CB2 receptor expressions have been shown higher in well-differentiated cancers compared to poorly differentiated ones . Moreovereceptor . On the iewed in ,215,216.iewed in ,217. Froiewed in  and Melciewed in  who showiewed in . Furtheriewed in ,207 founiewed in . The intiewed in . It was promoter . Recentlpromoter , in facty effect . CB1 recy effect  and elevy effect . Accordiy effect . Howevery effect , suggestAltogether these results underline a protective role for ECS in steroid-hormone-dependent cancers highlighting that the ES can regulate the ECS during tumor development and progression.C–jun −N terminal kinase typically involved in cancer cell proliferation [Although ECS is abundantly in the CNS and the role of estrogen is documented in brain development and in several physiological processes of the CNS like memory and learning ,104, untferation  empowersThe interplay between ECS and estrogen is well documented in brain development and several physiological processes of the CNS like memory and learning or the central control of reproduction; the same occurs at the periphery, primarily in the gonads and reproductive tract. Particular interest deserves the estradiol dependent expression of FAAH, the key enzyme in the modulation of endocannabinoid tone and therefore a primary actor in driving endocannabinoid signaling. In this respect, environmental factors like chemicals that mimic estradiol signaling or impaired levels of endogenous estradiol may have deep consequences for health, particularly on reproduction and behavior, by means of direct (or indirect) modulation of endocannabinoid signaling. ECS plays a protective role in steroid hormone-dependent tumors, but not in brain cancer. However, ECS may represent a prognostic/diagnostic/therapeutic biomarker for cancer and the simultaneous investigation of ECS and ES system may result useful for the development of pharmacologic approaches, particularly in diseases that show a very different incidence and maybe different features of pathogenesis in both sexes.


African American caregivers face unique challenges and strengths in addressing the needs of dementia care recipients. The purpose of the current study was to explore the roles of the familism and faith and service preferences and needs for African American dementia caregivers. Through collaborative partnerships among the research team, Alzheimer’s’ Association, Area Agency on Aging, and local churches, we obtained focus group and survey data (N=30) from African American dementia caregivers. Most caregivers were female (90%) and older than 51 years and had provided care more than 3 years. CGs showed strong cultural reasons  for providing care . Focus groups data, which was audio taped, transcribed, and analyzed by three researchers using content analysis, revealed three major themes related to dementia care experiences and needs. First, caregivers explained positive aspects of caregiving for both the individual caregiver and family . Second, caregivers also described negative aspects that pose substantial challenges such as lack of services, lack of balance in life, family conflicts over care, and mistrust based on their previous experiences with existing health care systems. Third, caregivers described their knowledge of dementia and shared their self-care and coping strategies and a need for support group services. The findings show an urgent need to implement culturally responsive services, especially in undeserved areas and populations, for caregivers to maintain or improve their emotional well-being and quality of care as well as family relationships.


To more rigorously examine the University of Rhode Island Cyber-Seniors Program, we conducted a quasi-experimental study to examine if older adult senior center participants (n=25) improved scores on social and technological measures compared to a sample of senior center participants (n=25) who did not take part in the program. Findings showed that participants improved on technology measures compared to the non-participants, including searching and finding information about goods & services, obtaining information from public authorities or services, seeking health information, sending or receiving emails, and participating in online social networks (p<.05). However, participants did not change on social measures. There is either a need to identify better social measures to understand the social benefits of taking part, or to bolster the program to aid in helping older adults alleviate isolation and loneliness. Information on best practices and challenges for gathering outcomes from older participants will be discussed. Part of a symposium sponsored by Intergenerational Learning, Research, and Community Engagement Interest Group.