Following on from the NASA twins’ study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA’s GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research.  Space medicine; Genomics; Proteomics; Space sciences. In fact, the scientific component of Artemis and other missions has acquired unprecedented importance. Within life sciences, molecular biology, genomics, and personalized medicine methods have progressed exponentially, and such techniques have been applied mostly in lower Earth orbit in experiments onboard the ISS. Consequently, spaceflight and space biology research will become significantly more important during the next decade. To support space omics, NASA, European Space Agency (ESA), and Japan Aerospace Exploration Agency (JAXA) communities have promoted several initiatives, such as GeneLab led by NASA,The European life science community in space research has always been limited in numbers but fully devoted to microgravity research, leading international progress in particular model organisms. In the last fifteen years, the financial crisis, together with the emergence of private partners for NASA, made ESA-related researchers vulnerable to the lack of crewed mission launch capabilities. This has particularly affected the space omics research in which ESA-funded activities were reduced. As a result, European Principal Investigators depended on collaborations with international colleagues to keep the pace in their research goals, in some cases with outstanding results, but undermining European independence.Space research careers at the university level should be encouraged in Europe. Several Master’s courses have been hosted by ESA, the European Low Gravity Research Association (ELGRA), and the International Space University (ISU) in recent years. However, the low number of students involved and the lack of a clear path for those students to pursue a career in the field reduces the impact of these academic plans. To retain talented young scientists and pursue excellence in space research, it is necessary to establish a strong network of European space biology research laboratories to promote student exchanges, from bachelor to post-doctoral level, as foundations to build a scientific environment that retains and attracts new researchers, particularly young post-doc researchers that will constitute the future of space research in Europe. Moreover, the timeline for progression of the career path in space research constitutes another major problem faced by junior researchers. To get permanent positions in laboratories in Europe requires an updated outstanding track record. However, spaceflight experiments require several years (sometimes decades) to be complete, from study conceptualization to the analysis of the results and publishing large amounts of data/studies, which then impacts the chances to attract funding, be part of evaluation panels, supervising students, and therefore, the ability to achieve a stable research position. Also, the lack of reproducibility and relative value of ground-based simulation facilities complicates obtaining clear and unquestionable results by space researchers. Choosing the space research path is choosing a hard path. Therefore, most junior researchers usually change their research topics to research fields, in which high-quality articles can be obtained at a faster pace. We should encourage junior life scientists in other fields to at least keep a “scientific arm” in spaceflight research.Now, we encourage the European research community to capitalize on existing capacities to boost space omics research via maintaining our collaboration/s with NASA GeneLab via ISSOP and similar international endeavors, but to also build our own facilities and capabilities in ESA member states in order to compete with NASA and other space agencies for attracting the new generation of space scientists. At the same time, it is important to work in international research announcements to maximize the results of large, reference experiments required to be performed in key model systems. ESA has provided a strategic roadmap for the future, but the continuous redefinition of those working plans, with little call for opportunities for scientists, does not allow concrete actions. On the contrary, NASA is promoting Technology and Integrated Discipline Engineering Services, including a continuum of support to the space research community including spaceflight opportunities, funding for laboratory activities, and even data processing support via GeneLab.As an ESA-funded Space Omics Topical Team, we have previously highlighted how the different funding scheme/s within the European Union (EU) is complex.The ISSOP consortium has highlighted that the reliance of space biologists leveraging omics approaches is increasing.The following section represents recommendations to ESA regarding specific topics chosen by the ESA-funded Space Omic Topical Team and their works in the context of international efforts omics approaches in space biology, we recommend and encourage ESA to significantly increase its funding investment and initiative that supports omics-based investigations and the generation of a European space omics database. This recommendation is not only regarding physical institutions but also “virtual” institutes focused on space-related projects, particularly if the critical mass of researchers is evenly distributed in Europe.Our Topical Team also suggests that ESA should take into consideration that there exists a chance for ESA to take a leading role in space biology publications due to the excellent research centers in all member states. However, unlike USA-based scientists that have been fully supported by NASA and federal administration, Principal Investigators in Europe are mostly isolated without a supportive critical mass of other scientists in their institutions or in other nearby research centers, which prevents multi-disciplinary coordinated investigations. Problems stemming from no multi-national coordination are for example lacking standards and certification processes for commercial spaceflight, conflicting national interests and regulations, the problem of increasing space debris and lacking planetary protection, as well as the language barrier when developing, translating, and adoption of standard operating procedures (SOPs). The latter has in the past been more difficult than developing SOPs. This could lead to other countries that are already very active on the subject taking over decisions. A final point to consider is that there exist different timelines and objectives from the private and public sector.In 2008, the United Nations Office for Outer Space Affairs (UNOOSA) developed a core education curriculum to its affiliated centers. This curriculum was developed containing five major fields of space applications, being: i) Satellite Meteorology and Global Climate, ii) Satellite Communications, iii) Space and Atmospheric Science, iv) Remote Sensing and Geographic Information Systems, and v) Global Navigation Satellite Systems.,,In Europe, we have a multi-faceted and strong life science community. This is reflected in various international collaborations inside and outside of the EU over decades with significant impact on, for example, the rapid development of vaccines against COVID-19. The EBI (part of the EMBL) is the principal source for training on big data in biology and together with the European Molecular Biology Organization (EMBO) provides training on omics experimentation and bioinformatic analysis in the continent.Regarding a career in space research, or more specifically space omics, multiple points were raised aiming to enrich Europe’s curriculum and availability. Since space omics is a relatively young branch of science in the EU  on developing life science resources across Europe could be crucial. The goal of ELIXIR is to coordinate these resources so that they form a single infrastructure and bring together more than 220 European organizations. In summary, there is excellent expertise in Europe from which ESA could benefit from to manage the huge increase of space life sciences data that is expected in the future, and to establish the necessary bioinformatics infrastructure, taking advantage of existing infrastructure. ESA Science Data Centers should collect inputs from ESA and European principle investigators to achieve a similar level of integration to other databases including GeneLab , ALSDA , BSP (Biospecimen Sharing Program), NBISC , and PSI . This does not necessarily mean to establish new databases with added value, but to create stable links and cooperation between the existing archive at ESA and both European (EMBL/EBI) and American (GeneLab) sources of space omics datasets. We also propose to assume a major role in the development of European sample biobank  to integrate European samples/data into NASA repositories in case an ESA/NASA agreement is not feasible.For this endeavor, the experience of ELIXIR (https://ibsls.megabank.tohoku.ac.jp/), an interactive omics database and sample sharing system of JAXA’s space mouse missions.The analysis of the whole genome data is not trivial and requires computing infrastructure and databases, as well as advanced bioinformatics solutions and expertise for large-scale data analysis. Prioritization in large-scale space technology research programs is inevitable and is already happening in NASA-supported research. NASA established GeneLab, an interactive and publicly available resource where scientists can store, share, and analyze the data from space-related experiments . JAXA also opened the Integrated Biobank for Space Life Science . There are no efforts to ban experiments with other specific partners. In addition, ESA offers potentially diverse opportunities  and there are a rising number of funding opportunities available with international organizations like ISS National Laboratory or the wetlab2 community. All this provides the opportunity for researchers to integrate their experiments into funded flights, which in turn encourages more and more scientists to participate in space research. Connecting financial support to technological advancements and industrial growth also encourages the rise of private rocket manufacturing entities. One such example is “The Exploration Company,” a German European spacecraft manufacturer, which produces the Nyx space capsule. This approach makes flight missions, primarily those centered around the ESA, more attainable. All of this leads to many new commercial spaceflight industry partners that could provide Europe exclusive rights to a fair share of payloads, which every European researcher could access regardless of costs and waiting times.Despite all this, European researchers find it extremely difficult to carry out space experiments because flight opportunities and project funding are not linked and calls are not well publicized, causing a significant dependency on collaborations to obtain funds that support experiments during space missions. Moreover, European scientists face other limiting factors such as the long timeline, sometimes years, of a space experiment as well as the geographical location of Europe, which is not the most suitable for launching rockets and limits the chances to launch space projects. All this suggests that Europe needs a significant increase on their own budget for research on the ground, the space, and flights that support their independence from other major world powers, lead partnerships with other international institutions, and protect the intellectual property rights that will secure their return on investments as royalties.Although ICT and Health that support life sciences are both high priority for the EU, space experimentation requires significant funding and scientific experts in very diverse fields integrated in these themes. Another observation is that digitalization of the Life Sciences & Health Sector is a priority for the EU. The low number of ESA-funded research projects, together with the impossibility of expanding laboratory infrastructures for space biosciences research in canonical, non-space specific research centers, prevents attracting space bioscience experts to Europe. It is also worth mentioning the long waiting period for access to ESA infrastructures, particularly to spaceflight opportunities. Therefore, we urge to promote space research to the same level as China and the USA to prevent Europe from being left behind in the standardization of space omics research.https://commercialisation.esa.int/) with the ambition to make Europe a space commercialization hub to launch and grow global space companies in technology and biomedicine sector. ESA Commercialization Gateway does not only provide its own space incubator and investor network but also invites researchers to apply for Commercial Applications enabled by Space Environments grants in collaboration with commercial spaceflight providers such as yuri GmbH, the space exploration company, and others.With the beginning of 2022, NASA have been prioritized funding opportunities for public-private partnerships with the goal of expanding capabilities and opportunities in space. ESA has responded with a similar effort by funding ESA Commercialization Gateway Which omic types and technologies have the highest potential for scientific return and clinical actionability ? - Genomic sequencing is likely to be the most immediately clinically actionable. Other omic types, including transcriptomics, microbiomics, and proteomics have potential clinical applications and may be useful for monitoring the effect of spaceflight throughout the mission.( 2)Which sample types are the most practical to collect ? - For frequent sampling, particularly in-flight, non-invasive measures including urine, saliva, skin swabs, and stool will be useful.(3)What metadata would be the most useful and practical to standardize alongside omics collection ? - Spacecraft environmental data will be essential as will regular performance data, such as those collected via NASA’s Spaceflight Standard Measures Program .(4)At which time points should omics be collected? - Pre-flight screening is recommended, and multiple pre-flight time points for dynamic omics are important for building a normalized baseline. Multiple in-flight omic time points are useful for monitoring change throughout the flight, including within the first few days where significant physiological changes already occur.(5)How can the artificial intelligence-readiness of the generated datasets beoptimzed? - Data and metadata should be standardized between human space omic studies and stored in machine-readable formats. Due to personal data challenges, it seems logical to ensure support for federated learning.In order to deploy a routine program, we must consider practicalities and logistics in detail, to design a cost-effective and standardized program. As such, in a recent manuscript from members of the ESA-funded Space Omics Topical Team, a number of considerations were introduced and a set of questions were suggested to motivate further discussion among experts and stakeholders.(1)What is the potential identifiably of different omic types, in the specific context of astronauts? - Astronauts are particularly easy to identify since they are a small cohort of public figures, with phenotypic information on individuals readily available online. This easily accessible phenotypic information could be combined with omic information through linkage attacks, to identify individuals and breach their privacy.(2)How should ESA go about obtaining meaningful informed consent for omics research? - Broad consent is often used for omics research , since analysis of omics data is not always hypothesis driven and future data uses are sometimes unknown. However, efforts should be taken to educate subjects as much as possible on the potential risks of having their omics data collected, and standard procedures such as oversight via ethical review boards should be followed.(3)How should ESA handle potential ethical issues, such as incidental findings and discrimination? - Similar to omic initiatives on Earth, clear policy which includes genetic counseling will be required for handling incidental findings, and regarding discrimination, focus should be given to using findings from omics to tailor countermeasures for individual crew members during spaceflight, especially if they are at a higher risk for a medical incident. An ESA Topical Team has recently discussed the opportunities for personalized medicine in space.(4)How should data storage and data sharing between ESA’s European and international network be handled? - Data sharing is desirable to enable open-science efforts, and NASA GeneLab is well established for data sharing of non-sensitive space omics data. However, most of the omics data are likely to be highly sensitive, so uploading sensitive data to a controlled access biobank, such as the UK Biobank and Federated European Genome-phenome Archive, to provide access only to approved researchers may make sense. Federated approaches, with the human omics data stored in local secure European biobanks, may also serve as an appropriate option for European-wide and even international data sharing.The second subset of questions pertains to the ethical, legal, and regulatory considerations of designing policy for European spaceflight omics studies in humans. Suggested questions for discussion and some initial recommendations are shown below.Several potential weaknesses and threads for European researcher’s participation in the space omics discipline development at a global level have been identified for which we provide recommendations to minimize these risks . Even ifThe ESA-funded Space Omics Topical Team aims to support the use of omics research among the ESA space biology community. The members of the Space Omics Topical Team are European affiliated scientists landing at the Space Biology research field as Principal Investigators from spaceflight biological experiments or as bioinformatics experts. The list of members contributing to this article are Daniela Bezdan, Joseph Borg, Thomas Cahill, Eugénie Carnero-Diaz, Henry Cope, Colleen S. Deane, Timothy Etheridge, Stefania Giacomello, Gary Hardiman, Raúl Herranz, Natalie Leys, Pedro Madrigal, Aránzazu Manzano, Felice Mastroleo, F. Javier Medina, Jakub Mieczkowski, Manuel A. Fernandez-Rojo, Keith Siew, Willian A. da Silveira, Nathaniel J. Szewczyk, Stephen B. Walsh, and Silvio Weging.


The Association of Maternal & Child Health Programs (AMCHP) and the Association of State and Territorial Health Officials (ASTHO) launched the PRISM  Learning Community, funded by the U.S. Department of Health and Human Services (HHS), Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB). The goal of PRISM was to build state and territorial health agency program and policy-making capacity to address substance use and mental health in the maternal and child health (MCH) population. Expanding access to care and treatment for perinatal substance use disorders (SUD) emerged as the issue of greatest need for state teams.The PRISM Learning Community consisted of three major components: (1) intensive capacity building for cross-agency state teams, which involved action planning, peer-to-peer learning, and technical assistance; (2) programming to inform the MCH field broadly about innovations in perinatal SUD policy and practice; and (3) a program evaluation involving pre-, mid-, and post-assessments and follow-up key informant interviews with state teams. This manuscript is not based on clinical study or patient data, therefore IRB approval was not required.States reported that their knowledge of perinatal SUDs increased and their cross-agency partnerships were strengthened as a result of their participation in PRISM. States identified four key priorities for their continued work: to improve multisector collaborations, to institute equitable SUD screening practices for pregnant people, to strengthen the perinatal behavioral health workforce, and to enhance Medicaid coverage for perinatal SUD prevention and treatment services. The need to respond to urgent demands of COVID-19 and the stigma associated with perinatal SUDs were the most significant barriers to advancing state action plan goals.Since 2018, the PRISM project has supported nine jurisdictions across two cohorts. Participation in PRISM advanced state policies and programs to improve perinatal SUD care through capacity building, technical assistance, and virtual programming. Findings and lessons learned from PRISM may inform the activities of other states seeking to address perinatal substance use disorders. What is Already Known About this Subject? The learning community model is known as an effective method of engagement for adult learning. Learning community models are currently being implemented for a variety of public health issues. Perinatal mental health and SUD care are widely studied from a clinical perspective and have gained national attention as a public health priority.What does this Study Contribute to the Existing Body of Knowledge? This report from the field describes state and territorial programmatic and policy efforts to improve the quality and accessibility of SUD care for perinatal populations through the PRISM Learning Community. Other jurisdictions may find the program and policy options helpful as they advance initiatives in their states to improve maternal and child health. Substance use, particularly the use of opioids, during the perinatal period is an ongoing and urgent public health concern. Women are at increased risk throughout their reproductive years (18 to 44) for developing a SUD; the highest risk occurs between ages 18 to 29 years old  to four organizations, including AMCHP and ASTHO. With their closely aligned constituencies, AMCHP and ASTHO formed a partnership, called PRISM - “Promoting Innovation in State and Territorial MCH Policymaking.”AMCHP’s mission is to lead and support programs nationally to protect and promote the optimal health of women, children, youth, families, and communities. AMCHP’s core membership is composed of senior leadership from each state and territorial Title V/MCH program. Since its founding in 1950, AMCHP has served as a national resource, partner, and advocate for state public health leaders and others working to improve maternal and child health public health systems. AMCHP builds the capacity of diverse state and territorial MCH leadership teams to use tools to advance innovative solutions to improve women’s access to care for mental health and substance use disorders.ASTHO’s mission is to support, equip, and advocate for state and territorial health officials in their work of advancing the public’s health and well-being. As a nonprofit organization, ASTHO is committed to supporting the work of state and territorial public health officials and their agencies and furthering the development and excellence of public health policy nationwide. ASTHO’s Maternal and Child Health team engages state and territorial health officials, and their agencies, to modify or enhance existing state-level policy initiatives that improve quality health care, including treatment for mental health and substance use disorders, for MCH populations.The PRISM Learning Community model was comprised of five components: (1) establishing cross-agency teams, (2) developing action plans, (3) participating in virtual and in-person learning opportunities, (4) facilitating peer-to-peer sharing, and (5) providing technical assistance. Participating states and jurisdictions were selected through a request for applications process. The learning community included two consecutive cohorts, and state teams are actively engaged in the learning community for a minimum of 12 months.As part of their application, jurisdictions were required to assemble a team of multiagency stakeholders, which included the state/territorial health official or designee, Title V/MCH director, substance use/behavioral health director and a Medicaid official. States were also encouraged to include representatives from the provider community, perinatal quality collaboratives, local health departments and community-based organizations. Connecting stakeholders across multiple agencies, reducing barriers to communication, and developing shared goals was instrumental to the success of participating jurisdictions.When they first began actively participating in the learning community, state teams engaged in facilitated discussions with PRISM staff to develop action plans. Using a root cause analysis or similar tool, teams identified challenges and barriers to implementing policy or programmatic approaches to addressing the needs of perinatal people with SUDs. Teams were also encouraged to identify topical areas in which they may have the highest collective impact and in which they may have existing programs or policies. Once barriers and challenges had been identified, teams developed one or two SMARTThe learning community model is structured to facilitate peer-to-peer sharing across jurisdictions. During in-person and virtual meetings, teams shared successes, lessons learned, and resources. Additionally, teams engaged in affinity group sessions during which they shared barriers to implementation and emerging issues with individuals who performed the same role. The PRISM team facilitated connections between jurisdictions and provided them a dedicated space to learn from one another.Learning community teams participated in virtual and in-person programming, which included policy academies, webinars, state share calls, and closeout meetings. During the policy academy, teams gathered to learn from federal and national partners and peers as well as engage in breakout learning sessions, action planning sessions, and panel presentations. Through webinars, the learning community teams had an opportunity to showcase promising, evidence-based, or evidence-informed best practices; learn from subject matter experts in the field; and share relevant resources. Topics included, but were not limited to, maternal mental health; SUD payment models; behavioral health integration and service co-location; universal screening and testing; nontraditional providers, including doulas and peer-recovery coaches; clinical guidelines ; health equity; and impacts of COVID-19. The PRISM webinars were open to the public, allowing them to serve as an important tool for educating the cohort teams and the MCH field at large about innovations in addressing perinatal SUD.ASTHO and AMCHP provided a continuum of technical assistance to support jurisdictional teams in developing and implementing action plan goals. The PRISM project’s technical assistance framework offered on-demand technical assistance, trends analysis and research, and technical assistance or expert consultation. Examples of technical assistance include connections to other jurisdictions and/or subject matter experts, policy scans and compilation of existing resources and tools. Additionally, AMCHP and ASTHO convened a stakeholder committee comprised of clinicians, public health professionals, and academics with expertise in perinatal SUD. Throughout the learning community, the stakeholder committee provided technical assistance resources, which included serving as webinar speakers, providing feedback on PRISM documents, and supporting state needs.To assess the impact of the learning community model on programmatic and policy success, the PRISM team utilized a comprehensive evaluation framework, informed by the project’s logic model Fig. . The evaCohort 1 included Arkansas, Iowa, New Mexico, South Carolina, Washington state, and the Commonwealth of the Northern Mariana Islands. Cohort 1 was actively engaged from February 2019 through January 2021 (24 months). The Cohort 1 evaluation concluded in mid-2021. All jurisdictions responded to the pre-survey, four responded to the post-survey, and four participated in interviews. All Cohort 1 jurisdictions are represented in the technical assistance analysis. Cohort 2 jurisdictions included Indiana, Missouri, and Nevada. Cohort 2 was actively engaged from May 2021 through September 2022 (16 months). The Cohort 2 evaluation is ongoing; therefore, only results from the thematic analysis of technical assistance requests include Cohort 2 results. All other results presented are from Cohort 1 only.Participation in the PRISM Learning Community provided access to space and guidance to create partnerships within teams and jurisdictions. The intent of the learning community was to support teams in developing and sustaining collaborative relationships with stakeholders. In the pre-, post-surveys, and interviews, responding teams indicated that partnerships across agency teams were strong and showed sustainability throughout the duration of the 15-month long cohort.“Our [PRISM] task force has been sustained over three years and has built strong partnerships among the members.” (Cohort 1 participant).While the learning community intended to shift indicators within health agencies related to “establishing roles and responsibilities that cross organizational boundaries” and “having regular effective communication,” the pre- and post-surveys revealed decreases in most teams’ self-reported effectiveness in these areas . Teams reported that the challenges of the COVID-19 pandemic was a key reason they became less effective than at the start of the learning community.“Unfortunately, communication has nearly stopped because of COVID.” (Cohort 1 participant).Among the four participating jurisdiction teams that responded to the post-survey, all agreed the PRISM Learning Community was valuable to their work, increased their jurisdiction or agency’s capacity, increased their knowledge related to their area of public health practice, increased the number of connections with peers from other health agencies, and helped improve cross-sector collaborations. Teams reported that in-person and virtual programming, along with technical assistance, supported them in accomplishing goals, bringing together national partners, creating networking opportunities, increasing connections, and helping centralize the conversation around state priorities and data. The programming and technical assistance also allowed states to reflect on what other states were able to accomplish with Medicaid funds.“I think [the PRISM Learning Community] helped with collaborative learning, learning from what other states have done and seen, what they were doing.” (Cohort 1 participant).AMCHP and ASTHO staff analyzed key themes across state team action plans and technical assistance requests to inform sustainability planning and future learning opportunities. Four key themes in jurisdictions’ response to perinatal SUD emerged. They included the importance of (1) leveraging multisector collaborations, (2) supporting equitable screening practices, (3) developing the perinatal behavioral health workforce, and (4) exploring opportunities to enhance Medicaid coverage for perinatal SUD.A foundational activity of the PRISM Learning Community was to establish multisector collaborations across various agencies and systems. Perinatal people with SUD interact with a range of stakeholders, including state and local health agencies, child welfare agencies, law enforcement, social service providers, Medicaid agencies, and hospital and medical systems. Multisector collaboration is increasingly necessary to provide comprehensive, coordinated, and equitable approaches to addressing SUD in perinatal people. One example of cross-sector collaboration is the Washington state PRISM team’s project, which brought together state agencies, housing advocacy organizations, and nonprofits to address the housing needs of families affected by the opioid epidemic and ensure low-barrier access to safe and affordable housing. PRISM team development and action plan strategies were largely rooted in and supported by this type of multisector collaboration.Cohort teams expressed interest in best practices and policy opportunities to implement and incentivize universal verbal screening for substance use during perinatal health care visits. Although people of color are no more likely than white people to use illicit substances during pregnancy, they are far more likely to be screened for substance use and reported to criminal justice and child welfare systems for substance use than their white counterparts (Harp & Bunting, Screening alone is not enough to ensure that individuals with perinatal SUD receive an accurate diagnosis, referral to a specialist, and family-based treatment (Byatt et al., Throughout the PRISM project, teams explored a variety of mechanisms to enhance Medicaid benefits and expand coverage for individuals with perinatal SUD. Jurisdictions expressed interest in adopting SBIRT into Medicaid programs as a cost-effective approach to early identification and intervention. If SBIRT billing codes are allowable within a state’s Medicaid system, providers can be compensated for their time; however, often restrictions are placed on provider types allowed to bill for SBIRT. Examples of Medicaid coverage for SBIRT were curated and shared with the learning community in an issue brief (AMCHP et al., Given the growing need for perinatal behavioral health care, the learning community also explored opportunities to expand the behavioral health workforce through Medicaid coverage for nontraditional health care providers, including peer support specialists, doulas, and community health workers. Nationally, these nontraditional health care providers are not yet widely available as a covered Medicaid benefit; however, several states have successfully launched their own Medicaid coverage of some or all of these providers (Medicaid, Overall, PRISM teams expressed a need to develop a more comprehensive understanding of the existing landscape of state and local perinatal SUD services, gaps, and opportunities to strengthen systems. Many teams requested technical assistance to explore strategies and policies from other jurisdictions related to their goals. These exploratory activities underscore the importance of learning communities in supporting policy development through state-to-state information sharing, access to subject matter expertise, and tailored resource development.Barriers to advancing perinatal SUD policies and programs were identified through the learning community’s assessments. The most prominent barrier faced by jurisdictions was the competing demands placed on health agency staff and partners due to COVID-19. As early as January 2020, state and territorial health agency staff were reassigned to COVID-19 response activities, which limited staff time and resources to devote to PRISM projects. PRISM teams also reported a lack of sustainable funding for perinatal substance use disorder activities as a challenge to their overall efforts.Notably, the stigma surrounding perinatal substance use was commonly cited as a challenge to providing high-quality, continuous care to pregnant and parenting people. It is well documented that people with SUD are at risk of stigmatizing and punitive interactions with health and social service providers, which frequently prevents people from seeking care or continuing their treatment Trainor, . At a stFrom 2018 to 2023, the PRISM Learning Community supported nine jurisdictions in advancing programs and policies supporting perinatal people with SUD. Through peer-to-peer learning and virtual programming, participants reported increased knowledge of perinatal SUD, strengthened interagency and cross-sector collaboration, and progress on action plan activities and goals. The four key priorities that emerged from the team’s action plans and technical assistance requests represent critical areas for future programming and technical assistance activities. As noted previously, these priorities are as follows:Leveraging multisector collaborations.Supporting equitable screening practices.Developing the perinatal behavioral health workforce.Exploring opportunities to enhance Medicaid coverage for perinatal SUD.The demands of the COVID-19 pandemic placed unprecedented strains on state and local health departments staffing and resources. This situation created a significant barrier to team engagement and resulted in delays in completing the learning community action plans. The AMCHP and ASTHO teams shifted from in-person convenings to virtual platforms, which potentially compromised full engagement and participation. When facilitating action planning sessions with Cohort 2, AMCHP and ASTHO ensured that the goals were impactful and attainable, considering the ongoing need to respond to the COVID-19 pandemic. Despite the pandemic, teams expressed a need to sustain momentum related to their goals and activities.To advance care and treatment for perinatal people with SUD, teams identified several programmatic and policy opportunities. First, they identified the importance of flexible funding to sustain activities related to perinatal SUD, especially when resources are diverted to emerging and urgent public health issues. In addition, they found that providing culturally competent, person-centered preventive care, treatment, and harm reduction services is key to reducing stigma associated with perinatal SUD. Furthermore, programs and policies should focus on ensuring health and racial equity. Finally, a cross-agency, cross-sector approach is critical to the uptake and advancement of care and treatment for perinatal people with SUD. Coordinated interventions at the local, state, and federal levels across disciplines could significantly improve perinatal mental health and SUD outcomes for MCH populations.The PRISM team acknowledges two limitations of the analysis. The data collected from participants were self-reported. However, during interviews, respondents were asked to provide additional context and examples related to reported changes in survey metrics. In addition, ASTHO staff conducted the key informant interviews and interpreted the data; therefore, staff potentially influenced the participants’ responses or interpreted the information with some bias.Findings from the PRISM Learning Community emphasize the need for improved quality care and treatment for perinatal people with SUD. A strengthened, coordinated public health response is necessary to address barriers to access, including stigma, financing and reimbursement, workforce capacity, and competing public health issues. PRISM Learning Community successes can serve as a model for states and territories seeking to improve the health and well-being of families in their own jurisdictions.


This special issue focuses on healthy aging and neuroprotection, particularly in the context of brain and physiological health during normal aging and Alzheimer's disease. It highlights the importance of physical activity, nutrition, and stress management in promoting healthy aging and preventing neurodegenerative diseases. The issue explores molecular pathways, genetic factors, and lifestyle interventions that support brain and physiological health in aging populations. Overall, the findings presented in this special issue underscore the importance of healthy lifestyles in promoting brain and physiological health during the aging process. The aim of this special issue is to provide insights on healthy aging. Research has shown that lots of factors affect healthy aging, from molecular to brain and physiology and to behavior and lifestyle. Among these factors, regular physical activity supports healthy aging including brain and physiological health and prevents aging-related disorders such as Alzheimer Disease (AD) , 2. For Moreover, during aging, many physiological processes occur such as cadiovascular system and respiratory system. Ribeiro et al provided an overview of the cardiac aging process with a focus on the following topics: cardiac structural and functional modifications, cellular mechanisms of cardiac dysfunction, genetics and epigenetics in the development of cardiac diseases and aging heart and response to the exercise . These rNutrition is essential for maintaining overall health, especially for the elderly. Citicoline is a natural metabolite present in all living cells and breaks down to choline and cytidine when ingested. Choline is pivotal for learning and memory and one of the important constituents of neuronal membranes and myelin sheaths. Choline deficiency is correlated with memory dysfunction . StudiesChronic stress is another impaortant factor that sensitizes aging processes and AD. Growing evidence points to chronic stress as one of the major risk factors for aging and AD, as it can promote the onset and development of AD-related pathologies. Liu et al provided a window of opportunity for more effective preventive and identifying therapeutic strategies for stress-induced AD .Amyloid beta (Aβ) and tau pathology have been shown in pathogenesis of AD, but the exact molecular mechanisms of AD remain elusive. Using caenorhabditis elegans model, an interesting report showed that the overexpression of activating transcription factor 7 (ATF7) significantly suppressed aging biomarkers and extended lifespan, suggesting that ATF7 is a longevity-promoting factor that lowers cellular senescence and inflammation in long-lived individuals . SimialrMany risk factors such as gene mutations associate with the onset of AD. Apolipoprotein E (APOE) is a well-established genetic risk factor for late onset AD and involved in regulating Aβ and tau pathology, inflammation, vascular integrity, glucose metabolism and vascular endothelial growth factor signaling. Importantly, growing evidence also indicates the role of APOE in retinal neurodegenerative diseases such as macular degeneration and glaucoma . These fTaking the prevalence of neurodegenerative Parkinson's disease (PD) as an example, a recent review targets the prodromal period of neurodegenerative diseases and proposes early lifestyle modifications to reduce risk facotrs and alter disease progression . For insIn conclusion, this special issue mainly focuses on the brain and physiology  health during normal aging and AD stage. Healty lifestyles such as physical exercise, nutrition, reduced stress and substance use support healthy aging and prevention and treatment of neurodegenerative diseases. Future research should consider using biomarkers to personalize prevention and intervention in aging.


To support the successful integration of community pharmacies into value-based care models, research on the feasibility and effectiveness of novel pharmacist-provided patient care services is needed. The UNC Eshelman School of Pharmacy, supported by the National Association of Chain Drug Stores (NACDS) Foundation, designed the Community-based Valued-driven Care Initiative (CVCI) to (1) identify effective value-based patient care interventions that could be provided by community pharmacists, (2) implement and evaluate the feasibility of the selected patient care interventions, and (3) develop resources and create collaborative sustainability opportunities. The purpose of this manuscript is to describe recruitment strategies for CVCI and share lessons learned. The project team identified pharmacies for recruitment through a mixed data analysis followed by a “fit” evaluation. A total of 42 pharmacy organizations were identified for recruitment, 24 were successfully contacted, and 9 signed on to the project. During recruitment, pharmacies cited concerns regarding the financial sustainability of implementing and delivering the patient care services, challenges with staffing and infrastructure, and pharmacists’ comfort level. To foster participation, it was vital to have leadership buy-in, clear benefits from implementation, and assured sustainability beyond the research period. The United States healthcare system lags behind its peers in terms of care quality, efficiency and patient outcomes. The U.S. consistently ranks last in health outcomes but spends the most at 16.8% of the gross domestic product, far exceeding peer countries . PharmacCommunity pharmacies are one of the most accessible healthcare access points with almost 90% of people in the United States living within 5 miles of a community pharmacy . FurtherTo support the successful integration of community pharmacies into value-based care models, research on the feasibility and effectiveness of novel pharmacist-provided patient care services is needed. In support of this goal, the UNC Eshelman School of Pharmacy, supported by the National Association of Chain Drug Stores (NACDS) Foundation, designed the Community-based Valued-driven Care Initiative (CVCI). This initiative had three aims. The first was to identify effective patient care interventions that could be provided by community pharmacists to improve care access, quality, and efficiency. The second aim was to implement and evaluate the feasibility of the selected patient care interventions in community pharmacies. The third aim was to develop and disseminate resources to educate other healthcare providers around the United States, as well as create collaborative sustainability opportunities by connecting community-pharmacy-based care intervention programs with other community healthcare partners as a foundational component of a sustainability strategy.The selected patient care interventions included a comprehensive diabetes program, a comprehensive cardiovascular disease program, and a behavioral health support program for depression and anxiety. After developing the interventions, including the creation of educational toolkits, the team set out to recruit community pharmacies for participation in the study. National and regional chain pharmacies, grocery store pharmacies, as well as independent pharmacies across the country were contacted for recruitment. Recruited pharmacies participated in the study for a period of 15 months consisting of a pre-implementation period (3 months) and implementation period (12 months). The purpose of this manuscript is to describe recruitment strategies and share lessons learned.Recruitment occurred from October 2020 through to June 2022. Throughout this time, the project team, which was composed of implementation science researchers and a community pharmacist consultant, met weekly to review potential pharmacy participants and discuss challenges to recruitment and implications to the initiative timeline.A list of potential pharmacy organizations was developed using a two-step approach. Possible research partners were first identified through the use of mixed data including an environmental scan and informal literature review, a review of applicable state prescriptive and collaborate practice agreement regulations, and stakeholder interviews and expert committee input. This list was then refined using a number of criteria to evaluate the potential fit based on the information gathered, including pharmacy type , state(s) where the organization operated, current patient care programs offered, culture of the organization, leadership, current capacity, and relationships. Following the selection of the three patient care services to be implemented, the initial recruitment list was revisited. Based on discussions of the initial fit information collected above and of the three available patient care services, the project team prioritized pharmacy organizations identified as being innovative, with a culture and leadership that promoted advancing patient care services and pharmacy practice. A recruitment target of three to five pharmacy organizations per patient care intervention was set.An initial email containing information about the research initiative and an invitation to participate was sent to each pharmacy organization using the contact information obtained during the pharmacy identification process. If no response was received within 7 days, a second email was sent. If no response was received after the second email, pharmacies were contacted via phone.Initial meetings were scheduled with each pharmacy organization’s point of contact and research team members to describe the research initiative and assess key considerations for “fit” using a checklist . The purUsing the combined results from the initial pharmacy identification process and the fit assessment, the project team considered the following variables in determining eligibility for participation: sufficient patient population for the targeted interventions, synergy with other patient care services, capability of staff and software, alignment with pharmacy organization priorities, support of leadership, and allowance through state legislation for the intervention. Pharmacies identified as meeting all necessary criteria were provided with a letter of commitment which outlined research initiative expectations. Upon receipt of the signed commitment letter, the pharmacy organization was established as a research initiative participant.The landscape analysis identified 42 potential community pharmacy organizations to contact. These included 20 chains, 21 independents, and 1 health system outpatient community-based pharmacy .Of the 42 pharmacy organizations identified in the landscape analysis, 24 were successfully contacted. Meetings were held with 22 of the organizations and 9 signed the commitment letter .Most of the pharmacy organizations that joined the research initiative were independents with single or multiple locations. Two regional pharmacy chains agreed to participate .Successfully recruiting community pharmacy organizations for participation in the research initiative proved challenging. During the recruitment process, the project team noted pharmacy concerns regarding the financial sustainability of implementing and delivering the patient care services, challenges with staffing and infrastructure, and pharmacists’ comfort level in providing care specifically for the behavioral health intervention. To foster pharmacy participation, the project team also found that it was vital to have leadership buy-in, clear benefits from implementation, and assured sustainability beyond the research period.Throughout the recruitment period, pharmacy organizations questioned the sustainability of patient care services following the completion of the research initiative. Many pharmacy organizations stated that there was not a viable path to sustainability for the patient care services without a financial model. This is a commonly described barrier to implementation of novel patient care services in community pharmacies ,13. WhilThe project team built in a planning (or readiness) phase for participating pharmacy research sites to prepare for implementation through pharmacy education, trainings and adequate staffing, identification of patient populations who may benefit from these services, development of the missing infrastructure necessary for implementation , integration of these services into existing patient care workflows, and working with leadership to ensure that these services were a priority for the pharmacy organization. This phase was guided by an evidence-informed readiness assessment and building process described elsewhere ,19. DuriThe behavioral health intervention proved to be the most challenging for recruitment. Community pharmacists can make a significant impact in behavioral health care around areas like screening and linkage to care, in addition to addressing adverse drug reactions, medication and disease state monitoring, and medication counseling ,29,30. HRegardless of individual pharmacist interest, without the support of organizational leadership, it was challenging to recruit pharmacy organizations. Leadership buy-in is a commonly cited facilitator for the implementation of new patient care services, as support from the top can either make or break organizational change efforts ,37. It iBecause recruitment started during the pandemic, the increased burden placed on community pharmacies at that time affected recruitment efforts. The Public Readiness and Emergency Preparedness (PREP) Act expanded the role of community pharmacists nationwide by authorizing and relying on them to provide COVID-19 vaccines, testing, and treatments, including for children and adolescents . This abDuring the CVCI recruitment period, the project team overcame hurdles to successfully recruit 21 community pharmacy sites from 9 pharmacy organizations. The challenges identified include concerns regarding sustainability, infrastructure, staff level of comfort with behavioral health services, organizational support, and the impacts of the COVID-19 pandemic. To address these challenges, we found that it was key to focus on pharmacy organizations that are patient care “innovators” with organizational priorities expressly aligned with the target interventions and mission of the research effort. Innovators, as defined by Rogers’ Diffusion of Innovations Theory, are those who are willing to take risks and act as change agents in their field . These iSuccessfully recruiting community pharmacies to adopt value-based patient care services hinges on meeting the needs of the pharmacies and reducing barriers prior to implementation. Community pharmacists have already demonstrated that they are valuable public health professionals ,47,48. BCommunity pharmacy participation in research is vital to inform the advancement of accessible, community-pharmacy-based patient care interventions that improve healthcare access, efficiency and outcomes. Researchers should consider how to overcome potential barriers to participation prior to the start of recruitment efforts. By ensuring that community pharmacies’ concerns are addressed up front, researchers may have greater success in recruiting community pharmacies for research participation.


This is of use for empirical analysis smallholder's sustainability trajectories given the pro-poor development policy support.The research and development needed to achieve sustainability of African smallholder agricultural and natural systems has led to a wide array of theoretical frameworks for conceptualising socioecological processes and functions. However, there are few analytical tools for spatio-temporal empirical approaches to implement use cases, which is a prerequisite to understand the performance of smallholder farms in the real world. This study builds a multi-agent system (MAS) to operationalise the Sustainable Agricultural Intensification (SAI) theoretical framework (MASSAI). This is an essential tool for spatio-temporal simulation of farm productivity to evaluate sustainability trends into the future at fine scale of a managed plot. MASSAI evaluates dynamic nutrient transfer using smallholder nutrient monitoring functions which have been calibrated with parameters from Malawi and the region. It integrates two modules: the Environmental (EM) and Behavioural (BM) ones.  Specification tableThe concept of sustainable agricultural intensification (SAI) is traced back to the mainstreaming of sustainability in development programs in 1980s  and a deAchieving SAI is a broad goal aimed at ensuring efficient use of resources for improved productivity, with equal attention to equity and environmental services . StrikinOf the five SAI components including breeding, nutrient input and recycling, pest and disease management, labour and mechanisation, and markets, it is purported that nutrient and fertility decline is the primary biophysical limitation to sustainability attainment . In smalIn the absence of established long-term trials, detailed typical farm analysis (TFAs) of nutrient balances for a few archetypical (cluster centroid) farms have been widely conducted to analyse (non-) performance using bio-economic models such as NUTMON and FarmDESIGN . These Tex ante assessment of impacts of policy interventions on land use and cover [Therefore, this study uses empirical sub-models to addresses gaps in bio-economic research on decision with geolocated and integrated datasets from plot level, soil, agronomic inputs and practices to policy drivers. In addition to plot level, a comprehensive review of scientific work in southern Africa and used to update the ecological modules for nutrient balance estimation. By integrating behavioural and ecological modules, we build the multi-agent system (MAS) which is well-suited for analysing social-ecological system's (SES) sustainable development  and is und cover . We analThe study applies the overview, design concepts and details + decision (ODD + D) MAS protocol by Railsback and Grimm . The ODDfarmtype1), medium input (farmtype2) and high input (farmtype3) farms. In the ecological system, the plot and landscape features also vary, which, coupled with household attributes, frame the differentiated decisions on soil nutrient distributions, yields, nutrient balances and economic benefits among human and ecological agents.Both the human and ecological farm entities are inherently variable . The houagents to apply, retain, reduce and enhance nutrient input-output flows such as fertilizer, manure and erosion  after a growing calendar year (t+1) is expressed as:X includes the nutrients NPK and the SOC, whilst ρ, C and D are soil density, coarse fragments factor and profile depth, respectively. The depth is set at 10 cm considering that the ridge spacing is 60, 75 and 90 cm and corresponding heights are 20, 25 and 30 cm [Nutrient balance results from integration of human induced flows and ecological flows have several sustainability implications. Of major concern is that low nutrient input leads to low food production and soil degradation. On the other hand, excessive application of major nutrients especially N and P can lead to nutrient draining into the environment causing pollution and low profitability. The total soil nutrient  framework  that hasagent, which is the farmland, hosts dynamic natural nutrient inputs like sedimentation and atmospheric deposition, and outputs like leaching, erosion and gaseous loses, that occur dependent on bioclimatic drivers and land use activities. The core EM assesses farm sustainability by evaluating natural material stocks and flows for the 10 m spatial resolution pixels across the landscape. The CROP-YIELD sub-module is estimated using generalized linear model (GLM) and analyses bounded maize and legume yields of the plot given the household livelihood profile, land productivity, soil fertility management (SFM) technologies and policies.The environmental The secondary module is the Behavioural Module (BM), which assesses nutrient flows arising when farmers as the active agents manage their farms to maximise productivity, through nutrient inputs: fertilizer, organic manure and legumes and outputs: yield and residue, which is contingent on available resources, farm conditions and policy interventions. For each input strategy, in a cropping season which is a calendar year in Malawi with uni-modal rainfall, farmers face two hurdles: first, whether to allocate available SFM to a plot/crop or not. Secondly, they decide to increase, maintain or reduce the amounts of inputs/outputs and land area to be covered. A double hurdle model is, thus, used, with the first using bi-logit model and the second using GLM. Both decisions are bounded by policies (input subsidy), natural capital , farmer livelihood profile , social capital (group membership) and linkages among complementary SFM practices.Legume- influences IN1Fertilizer-. Feedback-loop integration . The stet al. . Nested et al.  for a saPrimary data was obtained through farm surveys of soil, biomass and crop yields, nutrient inputs and outputs, and households. Secondary data included spatial data of soil types , soil nuIn determining the dynamic changes in usage of nutrient input technologies and the nutrient output processes, we examined the changes in exogenous policy actions but also controlled for the main internal factors. Among the various policies that most African governments provide, and communities appreciate as viable policy options to enable them to replenish lost nutrients and increase crop yields, the farm input subsidy program (FISP) is noticeably featured . EffortsAlthough the subsidy program is a pro-poor strategy aimed at reducing the nutrient gap, the sharing of coupon price and inputs makes it difficult to discern recipients from non-recipients, challenging an impact assessment. From our survey, we captured the total cost farmers paid for the fertilizer applied on a plot and divided with the market price to find the share of the subsidized input.The share of subsidized fertilizer applied to maize plots for the 2016/2017 growing season averaged 28 %. This was used as a baseline, and all policy and static variables were held constant but progressively changing variables such as age of household head and the cultivation period for the plot were updated. By bringing other factors to the baseline levels and project their progressive natural changes, the effect of policy interventions is therefore additional and conditioned on existing conditions. Four scenario spectrums were constructed based on the projected trend incrementally increasing or decreasing over the 20-year simulation period as: (a) current subsidy contributing an average of 25 %, vs. political aspirations and alternative policies that aim at (b) reducing subsidy to around 15 %, (c) reducing to zero, and (d) providing universal subsidy which is the vision of the current government.free” fertilizer might not be as committed to manage the crops as those who purchase the fertilizer, thereby having differentiated nutrient output flows.Fertilizer subsidy programs in Malawi have increased fertilizer access to many smallholders , with asAlthough there is no clear evidence on effect on subsidy on manuring, available evidence shows a high complementarity between fertilization and manure, with subsidy recipients apply comparatively less manure . Hence, Using the ODD+D framework, the attributes of farmers and farms, their states, actions and processes and responses to changes in subsidy regimes were calibrated and implemented in the NetLogo MAS language . We adopThe modelling steps and main procedures are presented in SET-UP’ button on the NetLogo user interface  is adequate, even if the rule of thumb of 10 SPV is followed. For instance, observation (451) to variable (21) ratio for maize yield estimation and prediction was 21:1 which gives reliable estimates. With yield model's SPV of 4, 8 and 6 for farmtypes 1, 2 and 3 respectively, the type-specific results may not reliably predict outside the dataset. However, for Monte Carlo simulations, recent studies have shown that the minimum SPV of two is adequate for estimation of regression coefficients, standard errors and confidence intervals . Hence, In addition to observation to variable ratios, the inclusion of variables in models from a whole set of 64 variables was done by differing specifications. Potential multi-collinearities among continuous variables were screened and only variables that were less correlated were included in the alternative model specifications (see Appendix S4). The Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) were used to select the model forms and functions that best modelled farmer SFM decisions and crop productivity . SeveralThe variability leads to yet another analytical challenge, stochasticity in estimated parameters. Stochasticity existed in the models for estimating nutrient distributions, and for predicting probabilities and intensity of input use, and crop production for the ABM. To ensure that the models are a representation of the real-world phenomena, several combinations of variables and parameters (replications) were used through machine learning algorithms. Uncertainty or stochasticity in soil estimation using the machine learning randomForest model was essentially managed by running tens to hundreds of replications for random subsets based on the knee bend method that indicates stability and validity . The simcurrent” scenario has been constructed based on the 2016/2017 subsidy regime averaging 28 % of fertilizer purchased to mimic real-farm conditions and shows predicted fertilizer and manure input and maize yield output (−1) increases for the whole population and high input farms (farmtype3) but slightly decreases for low and medium input farms (farmtypes 1& 2). The manure input is projected to have a stabilising trend while maize yields are projected to decrease. The maize yield gradient is expected as plots that were opened up recently in hillslopes are considered more fertile [The baseline “d output . Given s fertile . But wit fertile , product fertile . Factor Given the autonomy that farmers have to decide on nutrient replenishments on their farms , they tefarmmtype3) yielded more maize than those that only received higher fertilizer and moderate manuring (farmtype2). This has long-term implications on productivity, nutrient balances and profitability. Yet, manure input is still lower than the levels needed to supply nutrients [Juxtaposing the trend graphs, maize is much more responsive to manuring than fertilization. Maize yields for the farms that received both higher fertilizer and higher manure  [Five decades ago, the soils were naturally productive with 86 % of the farms realising economical yields without fertilizer input because soils had sufficient P and K . But as −1 UREA) . In the −1 UREA) . These r−1 UREA) .−1 and <5 ton ha−1 are below the 8 to 10 ton ha−1 annual organic inputs required to bring the soils to levels essential for fertilization response and structural stability [−1 of manure and could be self-reliant in terms of P and K, and potentially supply the SOC needed for structural stability and long-term productivity of the farms [The current manure and residue inputs of <1 ton hatability . These ehe farms .MASSAI is built as a multi-agent system (MAS) that operationalise the Sustainable Agricultural Intensification (SAI) theoretical framework for spatio-temporal simulation of farm productivity as a coupled human-environmental system. It is built by integrating the core ecological module with human behavioural module to capture, analyse and present nutrient stocks, flows and balances arising from farmer decisions and environmental processes. Considering the major policy intervention, subsidy, and the alternative regimes of universal subsidy or removing it alter the household input budget and behaviour, which impact sustainability outcomes including nutrient input levels, crop productivity and soil nutrient balance. It addresses problems of heterogeneity, interaction, stochasticity, and feedbacks among farming landscapes and land managers.The study found that within the fragile landscapes of Malawi, farmers strive to utilise the commonly available soil fertility management options as evidenced by wide but low usage. Nine in every ten households used inorganic fertilizers, a third planted legumes and almost half applied manures of various forms. From the empirical and simulated results, it is indicative that the maize mixed smallholder farming system in Malawi has become inelastic to changes in input policies. Despite the changes in subsidy, the total amount of fertilizer applied has levelled off.The evaluation of proximate and underlying drivers of choice and intensification of inorganic fertilizers, organic manures and legumes has shed light on the diffusion pathways and limitations. Though soil management in smallholder farming systems aims at addressing the most critical nutrient(s), the results from this study show that the soils in some areas are deficient in all three major nutrients  and SOC. Bearing in mind the inter-dependence as expressed by stoichiometry, continuous monitoring and adjustments need to be made to create optimal conditions for plant uptake. Considering the limited capacity on both demand for knowledge of soils by smallholder farmers and the supply of information by agricultural extension services, there is need to raise awareness, capitalise on digital tools to disseminate pixel-based soil information and input these into site-specific nutrient balance and crop yield models.Subsidy as a major soil nutrient management strategy was viewed by many as a panacea for productivity improvement, a replica of Asia's Green Revolution . The ini1.The parameterisation and the empirical models required for establishing the nutrient stocks and input and output flows are voluminous. Much as efforts were made to extensively review the literature for parameters, and a detailed survey data from representative farms have been used to customize the estimates for the study site, there are still cases where parameters established in other regions and generalised transfer functions have been used. As research in the region progresses, there is need to update the parameters and functions.2.To evaluate the impact of subsidy, most of the household attributes including labour, women empowerment, household resource endowments as well as plot attributes such as sizes, were not altered or updated. The stochasticity in these variables is captured by random assignment of their coefficient and confidence interval estimates in the SFM choice and production models. Further research should, therefore, build rules for updating these and test their effects by having different scenarios. In the current version of the model, rules for updating labour and gender have been provided and are being incorporated in the model.3.The modelling environment used, Netlogo, although widely used by ecological and social scientists to model human induced emergent phenomena, its computing capabilities for these small-sized heterogenous farms is limited to extend the model for application to larger landscapes and for other integrated socioecological processes.This study explored alternative soil management regimes, but the feedback mechanisms to inform policy making are yet to be fully established as indicated below.


The National Committee for Quality Assurance (NCQA) is an independent not-for-profit organization based in Washington, DC, whose vision is to transform health care quality through measurement, transparency and accountability. 1 Using the Health Plan Employer Data and Information Set (HEDIS), NCQA has determined how more than 90 percent of the nation's managed care organizations will collect, audit, and report their performance on a range of standardized quality measures. Many of the HEDIS measures are undisputedly useful in promoting population health, such as rate of beta-blocker use after myocardial infarctions or rate of cervical cancer screening. Other measures, such as antidepressant medication management (AMM), have less evidence supporting the goals promoted by NCQA. Although the latest report on the State of Health Care Quality 2005 from NCQA appropriately describes and cites support for the need to treat depression, it does not cite supporting trials that validate the definitions chosen for their AMM measures.


Individual geospatial data layers include roads, landings, ferries, churches, shops, mills, schools, hotels, towns with post offices, and towns with court houses. These data were digitized using Simon J. Martenet's (1866) Map of Maryland: Atlas Edition and contemporary geospatial road network data from the Maryland Department of Transportation.The geospatial dataset presented here represents historical middle 19 Specifications Table•th century road networks and settlement points of interest for key features of the Chesapeake Bay Eastern Shore region of Maryland, USA. The digitization of these data from a historical atlas in paper form allows for spatial analysis of the historical distribution of settlement features in the region within geographic information system (GIS) software.These geospatial data capture the distribution of historical 19•These geospatial data may be useful for geographers, historians, economists, planners, and other researchers interested in historical patterns of transportation, development, and culture.•These geospatial road network and settlement data were developed for the analysis of human-environment interaction in the function of the Underground Railroad in the Eastern Shore region of Maryland. However, these data can be integrated with other historical or contemporary geospatial data on changes to the natural, built, or social environments within GIS software to facilitate spatial analyses across various topical domains in the social sciences and humanities.•These geospatial data and the methodology for generating such data from historical sources provide an example for future related research in the spatial and digital humanities.1th century roads and other built environment features for the Chesapeake Bay Eastern Shore region of Maryland, USA, as derived from Simon J. Martenet's Map of Maryland: Atlas Edition, published in 1866 Digital geospatial data derived from historical maps provides a key resource for historical geographic and digital humanities research 2th century Chesapeake Bay Eastern Shore region of Maryland, including present-day Cecil, Caroline, Dorchester, Kent, Queen Anne's, Somerset, Talbot, Wicomico, and Worcester counties  shapefile format 33.1Martenet's Map of Maryland: Atlas of Marylandhttps://www.davidrumsey.com/): Cecil, Caroline, Dorchester, Kent, Queen Anne , Somerset, Talbot, and Worcester counties .A digital geospatial vector line data layer in shapefile format of road centerlines for the entirety of Maryland was downloaded from the Maryland Department of Transportation through Maryland's GIS Data Catalog  software package ArcGIS Pro , the current road centerlines shapefile was visually superimposed over the historical atlas map images. The individual lines in the modern road centerlines shapefile that comprised the analogous roads on the historical map were manually selected. The selected road centerlines representing the historical roads were then exported to a separate shapefile. The new historical roads shapefile was then manually edited while carefully reviewing the maps of the historical atlas to ensure accuracy, edit the shape or extent of the road linework for consistency with the historical map, manually digitize any additional historical roads not included in the contemporary road centerlines shapefile, and maintain topological integrity regarding road network connectivity .As with prior work generating geospatial data of historical mill locations and similar point features from paper maps The historical GIS data layers are made available in the North American Datum (NAD) 1983 Maryland State Plane coordinate reference system.3.4For validation, we collected historical data from alternative sources on the county-level counts of post offices, churches, and schools in order to compare these counts to those contained in the geospatial dataset generated from Martenet's (1866) atlas. Counts of churches and public schools for 1850 were collected from the 1850 US Census via the National Historical Geographic Information System With the exception of Somerset county, each of the counties in the geospatial dataset contain a greater number of post offices as compared to the validation dataset, with an average difference of three post offices per county. We speculate that some of the more remote or rural post offices may have served informally or were not tracked in official national US post office records of postmasters. The geospatial dataset tended to undercount schools and churches as compared to US Census Bureau records, particularly in Kent county. There are many more schools and churches than post offices and the MAE for schools and churches is higher as compared to post offices. Potential reasons for the disparity between the counts for the historical geospatial and validation datasets are that Martenet's survey simply did not identify all the schools and churches in the region or may also be due to changes which occurred between the survey and 1850 census data collection.This research did not employ human or animal studies. All data used in this research was publicly available and did not require special permission for use.Jeremy Mennis: Conceptualization, Methodology, Writing – original draft, Data curation. Kai Yuen: Data curation, Writing – review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Although there are several situations that can potentially lead to lower androgen levels, until now is not defined a syndrome or biochemical criteria to diagnose androgen deficiency in women. Benefits of androgen therapy in these situations are controversial.Girls with delayed puberty manifesting primarily as a lack of development of secondary sex characters and primary amenorrhea may be deficient in sex hormone production, including androgen production deficiency.Due to surgical menopause and premature ovarian failure, androgen levels may be reduced compared to age-matched normal controls.Young women with hypopituitarism, anorexia nervosa, and adrenal insufficiency may have lower serum androgen levels.The use of androgens and anabolic steroids for aesthetic purposes has increased considerably due to issues related to the cult of the body and beauty. However, this is associated with undesirable and potentially irreversible aesthetic manifestations, in addition to an increase in morbidity.There is no evidence for the use of androgen therapy in adolescent women, even in cases of hypogonadism due to ovarian (premature ovarian failure) or central causes.There is no evidence for routine androgen therapy in adult women with hypopituitarism, hypogonadotropic hypogonadism, adrenal insufficiency and anorexia nervosa.Androgen therapy, preferably by the transdermal route, may be considered for women with premature ovarian insufficiency (POI) or surgical menopause complaining of female sexual dysfunction (FSD), in addition to estrogen therapy.The use of androgens and anabolic steroids for aesthetic purposes is not recommended.The measurement of total testosterone or the calculation of the free androgen index can be used to control androgen replacement in women, but the available laboratory techniques do not present adequate sensitivity. Although the mass spectrometry technique has greater sensitivity, it is costly, which limits the use in clinical practice.In the female sex, androgen is produced by the ovaries and adrenals and by peripheral conversion. Circulating testosterone levels play an important role in musculoskeletal and cardiovascular health and sexual function (SF).This document will be divided into two parts, in which we will review current evidence of indications and contraindications for the use of androgens in different situations in a woman's life – during the reproductive period (part I) and during the climacteric period (part II).The most commonly dosed androgen in women is testosterone. In premenopausal women, testosterone levels do not vary significantly with cycle phase and there is a modest increase during the peak of luteinizing hormone (LH) in ovulatory cycles.The most widely used tests for measuring testosterone such as immunometric assays and radioimmunoassay, had limitations, with low accuracy for detecting physiologically low levels in women. Currently, the liquid chromatography-mass spectrometry assay has greater sensitivity for testosterone measurement, so it is considered the gold standard test.Although there is an association between serum androgen levels with sexual desire, its low level in women does not reliably predict clinical symptoms. Furthermore, testosterone levels are not independent predictors of SF in women. Thus, there is no biochemical diagnostic criterion to diagnose androgen deficiency in women.In adolescence, the activation of the hypothalamus-pituitary-ovarian axis stimulates the production of ovarian hormones, especially estrogens, responsible for the thelarche, pubarche and menarche in girls. In parallel, this activation also increases circulating testosterone levels, which, during adolescence and reproductive years, are produced in an equivalent way by theca cells and the adrenal cortex at a concentration of approximately 300 mcg per day.In adolescence, skeletal growth and bone mass gain are influenced by estrogens and androgens, with an important interaction between androgens, growth hormone (GH) and insulin-like growth factor (IGF-1).Although previous studies with different androgen therapy regimens in this age group in women with Turner syndrome and pan-hypopituitarism have shown some positive results such as bone and muscle mass gain and improved quality of life, they do not present enough evidence to recommend its use in female adolescents.Therefore, there is no recommendation for the use of androgenic therapy in adolescent girls in any formulation or route of administration due to the lack of evidence to confirm its efficacy and safety in this age group.Premature ovarian insufficiency and surgical menopause are two situations in which there is a reduction in androgen levels compared to women with preserved gonadal function of the same age, as well as in comparison to women with natural menopause.Hypopituitarism often includes hypogonadotropic hypogonadism and centrally-caused adrenal insufficiency, with a deficient production of androgens by the two major sources – ovaries and adrenals. A study that evaluated the use of 300 mcg testosterone patches for one year in 51 women with hypopituitarism showed an increase in bone mass in the hip and radius and in muscle mass, as well as improvement in mood and SF in this group of women.Women with adrenal insufficiency have lower levels of dehydroepiandrosterone (DHEA) and its sulfated form (SDHEA). Many women with primary and secondary adrenal insufficiency present deterioration in their general health status despite glucocorticoid and mineralocorticoid replacement.Women with anorexia nervosa have lower total and free testosterone levels than women without this condition.The current exaggerated cult of the body and aesthetic beauty has made many people seek quick results through substance abuse with the promise of better body image and physical performance. Among these substances are androgenic anabolic steroids (AAS),Empirical evidence suggested that AAS were used primarily by top-level competitive athletes and especially weightlifters, bodybuilders, and track athletes. Currently, AAS are widely used not only by athletes involved in recreational and minor league sports, but also by non-athletes.In Brazil, gestrinone, previously used for the treatment of endometriosis and discontinued because of its androgenic side effects, is now being marketed again in the form of an implant and called “beauty chip”, given a possible aesthetic effect )#x0028;reduction of body fat and promotion of lean mass gain). There are no studies evaluating gestrinone for improved libido or lean mass gain, as well as its long-term effects, such as possible carcinogenic risk or secondary infertility. This product is not approved for use by the National Health Surveillance Agency (Anvisa), and the Federal Council of Medicine only recommends the use of hormonal implants for medical purposes, given the lack of any evidence of the promised aesthetic benefits.Users may associate different AAS, as well as with other potentially anabolic products such as GH and insulin for better results, although with an increase in androgenic and metabolic effects.In women, the most frequent alterations attributed to AAS abuse are menstrual irregularities , dysmenorrhea, anovulation, acne, alopecia, clitoris hypertrophy, libido alterations, breast tissue atrophy and uterine atrophy, many of which are permanent.Therefore, we do not recommend the use of AAS for aesthetic purposes. This use is illegal, can cause addiction, and numerous harmful side effects.The effects of COCs on SF remain controversial. In order to improve SF, some authors have proposed the concomitant use of androgens, especially DHEA. The exchange of ethinylestradiol for 17β-estradiol is also suggested, with a lower elevation of SHBG and a higher index of free androgens. However, there is lack of evidence on the impact of COCs on SF, and on the fact that this dysfunction is caused by a reduction in androgenic activity.There is limited evidence on the use of androgens in women during the age compatible with the reproductive period, indicating their use in situations of bilateral oophorectomy and premature ovarian insufficiency. There is a lack of evidence to support other indications. The use of androgens for aesthetic purposes should not be recommended.National Specialty Commission on Gynecology Endocrinology of the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO)President:Cristina Laguna Benetti PintoVice-President:Ana Carolina Japur de Sá Rosa e SilvaSecretary:José Maria Soares JúniorMembers:Andrea Prestes NáculDaniela Angerame YelaFernando Marcos dos ReisGabriela Pravatta RezendeGustavo Arantes Rosa MacielGustavo Mafaldo SoaresLaura Olinda Rezende Bregieiro CostaLia Cruz Vaz da Costa DamásioMaria Candida Pinheiro Baracat RezendeSebastião Freitas de MedeirosTecia Maria de Oliveira MaranhãoVinicius Medina Lopes