Although enhancing resilience is a well-recognized adaptation to climate change, little research has been undertaken on the dynamics of resilience. This occurs because complex relationships exist between adaptive capacity and resilience, and some issues also create challenges related to the construction, operation, and application of resilience. This study identified the dynamics of temporal, spatial changes of resilience found in a sample of wheat–drought resilience in Australia’s wheat–sheep production zone during 1991–2010. I estimated resilience using principal component analysis, mapped resilience and its components, distinguished resilient and sensitive regions, and provided recommendations related to improving resilience. I frame that resilience is composed of social resilience including on- and off-site adaptive capacity as well as biophysical resilience including resistance and absorption. I found that resilience and its components have different temporal trends, spatial shifts and growth ratios in each region during different years, which results from complicated interactions, such as complementation and substitution among its components. In wheat-sheep zones, I recommend that identifying regional bottlenecks, science-policy engagement, and managing resilience components are the priorities for improving resilience. Resilience Alliance3 defined resilience as the ability of a SES to absorb shocks and regenerate after disturbances before exceeding the system’s threshold for stress tolerance. Resilience comprises resistance, absorption, and capacity for restoration that is sometimes called adaptive capacity (AC)4. Resistance, the capacity to withstand disturbance and recover from it, are both components of ecological resilience5. Capital theory links resilience to economics, sociology, and ecology6, and improving resilience is closely related to building human, social, and political capital7. In this sense, resilience theory provides a method to manage dynamics of the SES, which includes the adaptive management techniques related to sustainable development8. Consequently, enhancing resilience has been adopted as a systemic approach of embedding and integrating the multifaceted and articulated nature of vulnerability and resilience to climate disasters10.Ever since the theory of resilience was first proposed11, and increasing AC is a critical part of improving the resilience of SES12. Any dynamic SES has a combination of resilience, adaptation, and vulnerability13, and AC affects the cycles of resilience and vulnerability simultaneously14. However, different adaptive options may impede the development of resilience15. Local adaptability may unintentionally reduce regional resilience and increase regional vulnerability16. An increase in AC of a SES in one region may cause another region to lose resilience17. The synergistic effects of the resilience and uncertainty of AC can make ecosystems more vulnerable to changes; therefore, the combination of active adaptive management and governance of resilience will require managers to examine the dynamics of AC and resilience18. The reasons for the complexity of the relationship between AC and resilience involve complementation and substitution among their various components in the context of the dynamics of resilience. The complementation comes from a positive causal relationship between indices and substitution from a negative causal relationship between indices19. For example, substitution among sources of the effects of output and competition for input affects the regional distributions of the impacts of climate change on dairy productivity in Australia20.However, the complex relationship between resilience and AC has continued to be debated during the last decade. AC is the ability to reduce potential damage and take advantage of new opportunities21; the simple definition of “resilience of what to what” conflicts with problems related to vagueness and malleability when compared to other measurements of resilience22. At an operational level, although each aspect of resilience has been expressed as a set of empirical indicators, measures of the totality of resilience is still unclear23, quantifying resilience is notoriously difficult that impedes to built through developing AC24. At the application level, the complicated relationship between vulnerability, resilience, and AC causes a gap between science and policy25. As a central concept to the accurate definition of resilience, the idea of “bouncing back” or interaction can be interpreted differently under three different narratives that can inspire different policies26. Therefore, dynamics of resilience cannot be clearly defined, measured, or implemented at spatial and temporal scales.The dynamics of resilience refers to changes in resilience after shifts in temporal or spatial objectives, so it is difficult to define, measure, operate, and implement when the context changes. Additionally, resilience involves addressing issues at the conceptual, operational, and application levels. The conceptualization and applicability of resilience are still vague when used in the theory and practice of disaster risk managementThis paper aims to estimate resilience and assess the dynamics of resilience. I subsequently determine how to build resilience in different regions and at different times as constrained by local capital features. Specifically, the study has three main objectives. The first is to frame resilience, for which we used the case of resilience of Australian wheat to drought. The second objective is to examine the dynamics of resilience, that is, interactions such as substitution and complementation among resilience and its components at different times and in different regions. The third is to investigate the implications of such dynamics of resilience such as they may render different regions either resilient or sensitive and to assess the benefits of building resilience in a given region, so that I find an optimal resolution to developing regional resilience according to some regional capital constraints.My work contributes to resilience research at the conceptual, operational, and application levels. First, I offer new synthesized method of studying resilience, combining sustainable livelihood framework (SLF) with the Principal Component Analysis (PCA) method through the use of a spatial map and a radar map. Second, this study shows that resilience is composed of social resilience including on- and off-site AC as well as biophysical resilience including resistance and absorption. Third, I found dynamic resilience to have different temporal trends, spatial shifts, and growth ratios in wheat-sheep zones from 1991–2010, which results from complementation and substitution between its components in the process of climate change. Overall, it provides useful information for local policy makers as well as for individual households designed to help them improve the resilience of wheat crops to drought.My study areas are all located within Australia’s wheat–sheep production zone , provide data related to the resilience of Australian agriculture, which helped me to analyze the rural capital that supports rural livelihoods and the resilience of wheat to climate change in the wheat–sheep production zone (http://www.agriculture.gov.au/abares/surveys).Second, many studies have assessed the vulnerability of crops to drought in Australia’s wheat–sheep production zoneThe dynamics of resilience were assessed adopting the methodological work-flow illustrated in Fig. 35. Social resilience is defined as the ability of human communities to withstand external shocks23. In wheat-drought resilience, resistance refers to the ability of wheat to tolerate drought, as represented by the benefits from the humid climate; absorption denotes crop mitigation to drought as measured from actual wheat yield; restoration refers to the ability of the crop to recover its pre-stress status, as determined by farmer’s AC, which incorporates human, social, natural, physical, and financial capital.To capture the totality of resilience, I here framed resilience as a combination of social resilience including the on- and off-site AC and biophysical resilience that is composed of absorption and resistance. I used capital indicators from socioeconomic and ecological indicators from ecology. Biophysical resilience represents the magnitude of disturbance a system can handle before moving into a different state36. In arid and semi-arid regions, beneficial drought resistance indicators, such as canopy temperature, stomatal resistance, and rate of water loss, have a significant relationship to the yield reduction ratio37. In northern China, drought index is the most comprehensive drought resistance index, and it also includes the opposite yield (drought resistance coefficient) and absolute yield of the wheat variety38. Therefore, I predicted wheat yield under special climatic conditions to assess climate change, and actual yield in the past few decades to determine the reductions in yield due to the drought. I measured wheat–drought resistance using a wet index (WI) calculated using predicted wheat yield and wheat-drought absorption using wheat harvest index (WHI) measured by actual wheat yield. The predicted wheat yield is weighed by the area sown to wheat (produced) in the National Land Use Map of Australia in 2006, and were simulated at 50 kg N ha−1 from 1991–2010 using APSIM version 7.339.Most measurements of resistance and absorption of crop to drought have been found to be related to the crop yield and drought in previous works. For instance, the stress susceptibility percentage index (SSPI), relative drought index (RDI), abiotic tolerance index (ATI), stress non-stress production index (SNPI), and drought resistance index (DI) are considered the most suitable indicators for screening drought-tolerant cultivars41. As the stock of knowledge, talent, skills, and abilities of farmers, human capital includes labor productivity expressed by total labor used (TLU) on a farm, and management ability expressed by the age of a manager (AM). Social capital is an appreciable and convertible long-lived asset and collective good that has relationships with other actors that need maintained continuously. Its effects flow from the information, influence, and solidarity it makes available to the actor42. Social capital is mainly embedded in the social networks between individuals and organizations; annual telephone charges (TC) are an indicator of social connections and knowledge sharing. Natural capital refers to some natural resources that supply environmental services and goods, such as water and erosion control; here, its proxies are crop productivity (crop-revenue level: CRL) and the soil water-holding capacity (SWHC). Physical capital, the long-term existence form of production materials, here includes land value and improvements (LVI) and expenditure for electricity (EE). Like any kind of money, financial capital combines total closing capital (TCC), access to financing (AF) and total cash income levels (TCIL)  and biophysical resilience, respectively.In Table At the operational level, the dynamics of resilience can be expressed by temporal and spatial shifts of resilience and its components in the maps. Figure The trends of SR, AC, PC1, PC2, and PC3 have complicated change every five years in the longitudinal view of the Fig. 45.Each PC, SR, and AC increased absolutely from 1991 to 2010, with different growth ratios in different regions at different stages Fig. . The higIn the study, a new synthesized method of studying resilience was used to combine SLF with the PCA method and geographical information systems (GIS) and ARCmap. Specifically, I (1) provide a framework for assessing resilience that includes AC, resistance, and absorption, (2) use principal component analysis (PCA) to integrate resistance, absorption, and restoration (AC) into resilience, (3) map the spatial and temporal dynamical trends of resilience and its components, (4) classify the resilient and sensitive cases according to annual and five year indicators in each region, and (5) recommend building components to improve resilience based on regional constraints. The PCAs integrate each indicator into principal components (PCs) that are then decomposed into executable policies. The geographical maps of resilience, AC, and their PCs can provide useful information that will allow householders to understand the dynamics of resilience and the interactions between their components. More detailed radar maps of livelihood capital can improve the targeting and effectiveness of local policies of the government and livelihood strategies of households by showing the local constraints in each region. Comparisons of different spatial maps of PCs and radar mapping of the livelihood capital can help determine the rules controlling resilience as it relates to climate change. There are at least five advantages of this synthesized methodology. It (1) illustrates the rules governing spatial and temporal shifts in sharply visual ways, (2) matches the integration and typology of resilience and its components, (3) explains substitution and complements between different indexes by comparing lines and maps, and (4) provides useful information for decision-making at both the household and policy levels.17; for instance, rising ratios of PC3 in the Central and Southern Wheat Belt caused a decrease ratios of PC3 in the Northern and Eastern Wheat Belts of West Australia in 1996–2005 , the substitution between high PC1 and medium PC2 initiates the neutral AC during 1996–2005, while the complement between high PC1 and high PC2 aggregates into high AC during 2006–2010  can augment the resistance of wheat to drought. Selecting efficient technologies  can improve the tolerance of wheat to drought. Managing AC depends on developing human, physical, social, natural, and financial capital in socioeconomic contexts. For example, specific investments in education and health services can increase human capital, and programs that support community development and communication infrastructure, such as Australia’s land care movement, can enhance social capital. Policies that accelerate rural development and expand access to the markets can create better physical infrastructure and provide additional market opportunities48.Creating scientifically sound policies to manage the components of resilience  will help local stakeholders deal with climatic disasters. Biophysical resilience benefits from improving resistance and absorption in the environment49.The science-policy gap also should be resolved by managing the components of resilience. To make science more relevant to policy, resilience assessments need to inform action by and on behalf of stakeholders to increase resilience and build AC. The government, scientists, and non-government organizations should provide farmers with a decision-support system, seasonal weather, and agricultural forecasting as well as information related to the effects of climate change on farming systemsAlthough enhancing resilience is a well-recognized adaptation to climate change, little research has been undertaken on the dynamics of resilience. This occurs because complex relationships exist between AC and resilience, and some issues also create challenges related to the construction, operation, and application of resilience. This study identified the dynamics of temporal, spatial changes of resilience found in a sample of wheat–drought resilience in Australia’s wheat–sheep production zone during 1991–2010.Combining SLF with the PCA method through spatial resilience mapping, I provide a synthesized methodology of resilience, expand knowledge on the dynamics of resilience, and recommend effective strategies of improving resilience, which are useful and urgently needed for resilience conceptualization, operation, and application. I conclude that a synthesis of resilience is needed to create an interaction between social and biophysical resilience due to the substitutions and complementation events among their components, recommend that preferentially solving regional constraints, building components of resilience, and trading off the related components are the important steps required to improve resilience.However, the present analysis has some limitations. First, the measurements of the resilience of wheat yield to drought lost more information on the decision-making process about improving resilience. I will measure resilience of agricultural profit to climate changes. Second, it exemplifies here how complements and substitutes between each PC affect resilience; these complex interactions may reduce the effectiveness of the SLF in resilience assessments. The tradeoff among these interactions will be an interesting topic for future studies.


Social relationships, which are contingent on access to social networks, promote engagement in social activities and provide access to social support. These social factors have been shown to positively impact health outcomes. In the current systematic review, we offer a comprehensive overview of the impact of social activities, social networks and social support on the cognitive functioning of healthy older adults (50+) and examine the differential effects of aspects of social relationships on various cognitive domains.We followed PRISMA  guidelines, and collated data from randomised controlled trials (RCTs), genetic and observational studies. Independent variables of interest included subjective measures of social activities, social networks, and social support, and composite measures of social relationships (CMSR). The primary outcome of interest was cognitive function divided into domains of episodic memory, semantic memory, overall memory ability, working memory, verbal fluency, reasoning, attention, processing speed, visuospatial abilities, overall executive functioning and global cognition.Thirty-nine studies were included in the review; three RCTs, 34 observational studies, and two genetic studies. Evidence suggests a relationship between (1) social activity and global cognition and overall executive functioning, working memory, visuospatial abilities and processing speed but not episodic memory, verbal fluency, reasoning or attention; (2) social networks and global cognition but not episodic memory, attention or processing speed; (3) social support and global cognition and episodic memory but not attention or processing speed; and (4) CMSR and episodic memory and verbal fluency but not global cognition.The results support prior conclusions that there is an association between social relationships and cognitive function but the exact nature of this association remains unclear. Implications of the findings are discussed and suggestions for future research provided.CRD42012003248.PROSPERO 2012: The online version of this article (10.1186/s13643-017-0632-2) contains supplementary material, which is available to authorized users. Cognitive functioning plays an important role in determining functional abilities, quality of life and independence in older adults , 2. AlthOne difficulty when trying to determine the effect of social relationships on cognitive function is the use of discrepant and unclear definitions of different social factors . If reseResearch examining the effects of social relationships on older adults’ cognitive functioning most commonly assesses the frequency of engagement in social activities , followeConsideration should be given to possible effects that different aspects of social relationships may have on specific cognitive processes –38, as eFrom a theoretical perspective, there is clear reason to expect an association between social relationship factors and cognitive outcomes. Social activities may include a type of cognitive stimulation, thus contributing to cognitive outcomes via the building of cognitive reserve ; cognitiFew literature reviews provide a comprehensive overview of research on social relationships and cognitive function in older adults. Structural and functional aspects social relationships are not often differentiated or separately assessed , precludThe aim of the current review was to evaluate the association between different aspects of social relationships; specifically social activity, social networks, and social support, with the cognitive functioning of healthy older adults with no known cognitive impairment. This is the first review to include data from available RCTs and genetic (twin) studies alongside an updated summary of observational evidence. The review is also innovative in its attempt to account for the differential effects of various factors associated with social relationships on specific cognitive domains Fig. .Fig. 1ThPubMed, Medline and PsycInfo were searched to identify RCTs, observational, and twin studies written in English and published between January 2000 and January 2017. The original search was conducted in 2015, and was updated in 2017. Search terms included ‘social activity’, ‘social engagement’, ‘social intervention’, ‘leisure intervention’, combined with ‘cognition’, ‘cognitive performance’, ‘cognitive decline’, ‘cognitive function’ and ‘healthy elderly’, ‘older adults’  guidelines. The following inclusion criteria were used: (1) peer-reviewed and academically published observational, RCT or twin studies that 2) investigated the impact of engagement in social activities, social networks or social support on cognitive function and (3) included a sample of community dwelling older adults (> 50 years) with no known cognitive impairment. We excluded studies if participants had been diagnosed with any cognitive impairment, cardiovascular disease, or other significant medical, psychiatric or neurological problems; or studies that combined data from participants with cognitive function within the normal range with data from participants experiencing cognitive decline  measure of verbal fluency . CompareTwenty-two observational studies examined the impact of social activity on cognitive function. At baseline, there were significant associations between social activity and higher scores on five out of five measures of global cognition , 58–60; Nine observational studies examined the impact of social networks on cognitive function. Five studies examined network size and frequency of contact with members of the social network together , 74, 75 Nine observational studies examined the impact of aspects of social support on cognitive function. At baseline, there was a significant association between emotional support and improved outcomes on four out of five measures of global cognition , 58, 76,At follow-up, scores on measures of global cognition were positively correlated with social support . EmotionThree studies examined the impact of social relationships on cognitive function. At baseline, lower scores on CMSR were associated with poorer verbal fluency and two (out of two) measures of episodic memory . At follTwo twin studies examined the impact of social activity on cognitive function. One study reported significant positive correlations between social activity and initial scores on two measures of global cognition . DiscordAcross the four distinct aspects of social relationships, evidence suggests a relationship between (1) social activity and global cognition, overall executive functioning, working memory, visuospatial abilities and processing speed but not episodic memory, verbal fluency, reasoning or attention; (2) social networks and global cognition but not episodic memory, attention or processing speed; (3) social support and global cognition and episodic memory but not attention or processing speed; and (4) CMSR and episodic memory and verbal fluency but not global cognition.In RCTs, social activity improved global cognition and increased brain volume but did not impact domains of memory, attention, verbal fluency, processing speed or overall executive functioning. Longitudinal associations were reported between social activity and global memory measures, overall executive functioning, working memory, visuospatial abilities, processing speed and global cognition but not episodic memory, verbal fluency, reasoning or attention. Genetic studies showed associations between social activity and memory and global cognition but not overall executive functioning, verbal fluency or processing speed.social working memory (SWM) that describes working memory as essential for navigating the complexities of the social world [Social activity was most consistently associated with improvements on global cognition, as measured by global or composite measures of cognitive function, across all study-types. This replication of results is encouraging, particularly since multiple studies investigated the impact of social activity on global cognition, and suggests that social activity may be useful for promoting brain health in older adults. The included longitudinal and genetic studies also showed that social activity was associated with some (i.e. working memory) but not all  executive functioning domains. Although our results fail to support those of Brown et al.  who repoal world , and sugSimilar to the findings for social activity, the results show that larger social networks and greater levels of social support were associated with improved global cognition. There were also differential effects of the type of social relationships on specific cognitive domains. Social support was associated with benefits to episodic memory but social activity and social networks were not. One explanation for differing effects of social support versus social activity and networks may be the impact that social support has on stress. Social support has been shown to promote resilience against the negative consequences of stress  whereas Social networks and activity are related concepts and both are structural dimensions of social relationships , and indScores on the outcome of CMSR were associated with verbal fluency but not global cognition and the findings regarding episodic memory and CMSR were inconsistent. It is difficult to draw any conclusions regarding CMSR because this composite score does not allow the determination of the differential effects of each specific social relationship-type. Future studies would benefit from ensuring consistency and specificity in defining and measuring distinct aspects of social relationships.Overall, the results show that social relationships, as defined in this review, benefits older adults’ cognitive functioning. Changes in the characteristics of social relationships could be a consequence of cognitive decline as opposed to a cause however . The finContradictory research has reported that cognitive decline and decline in perceptual speed does not predict decline in social relationships or function , 60, andWe found it difficult to identify RCTs that included social relationships as either intervention or active control components. The search terms used may not have identified RCTs that focused on alternative lifestyle factors such as exercise that might have included social relationships as an active control condition, meaning that we may not have included all relevant RCTs. In addition, databases were only searched from the year 2000 to 2017, and Medical Subject Headings (MeSH) were not used meaning that some relevant studies may have been omitted. This was somewhat controlled for through supplemental searches of reference lists of included studies. The more pertinent issue is the fact that there are so few RCTs published that primarily focus on social interventions. This is most likely due to the difficulty in forming appropriate control conditions, although socially isolated older adults are not uncommon—however, they are, by their very nature, a difficult group to access for research. An RCT that recruited socially isolated older adults into four conditions: (1) social activity, (2) social networks; (3) social support; (4) wait-list control and examined outcomes on cognitive and social functioning measures would provide important insights.The heterogeneity in definitions and measures of social relationships and cognitive function resulted in difficulties collating research evidence in a meaningful way and precluded us from conducting a meta-analysis. To promote homogeneity, future research could use the categorisation and definitions of social relationships as outlined in this review. Studies would benefit from an agreed appropriate battery of cognitive tests to be used when examining each distinct aspect of social relationships; for example, measures of episodic memory might be more important when investigating social support than networks or activity, and studies would benefit from including measures of global cognition and working memory for all social relationship-types. Systematic reviews consistently call for standardisation of tests measures to improve replicability and test the reliability of individual study findings, and yet standardisation and replication remain largely absent from this literature. Future RCT and longitudinal studies need to replicate prior studies with a view to strengthening existing evidence and determining the exact nature of the association between social relationships and cognitive function.Exploring the impact of social relationships as distinct from cognitive, leisure or physical domains of activity is questionable, since all social behaviour includes aspects of these three domains of activity and it is not possible to isolate purely social factors. Many leisure activities have a physical  or cognitive (playing chess) element which impact on cognitive processes and may confound measurement of social behaviour. To design effective RCTs, researchers could design interventions that include social activities, networks and support, and ensure these are clearly defined and consistently used across studies to improve comparability of results. It would also be helpful to avoid incorporating clear physical exercise or cognitive stimulation in social interventions which may confound results. Future research might also consider the impact of technology, internet and social media on social relationships, particularly feelings of social support.Loneliness was not considered in the current review. While previous meta-analyses and reviews have investigated loneliness and social isolation together , 95, witResearchers suggest that the size of the association between social relationships and cognition is similar to that of age and cognition , 72. OurAdditional file 1:Search results. Table of search terms and results as used in the systematic literature search. (DOCX 19 kb)Additional file 2:Excluded studies. Table of studies excluded from the systematic review. (DOCX 28 kb)Additional file 3:Risk of bias in RCTs. Table including information regarding the risk of bias assessment conducted on RCTs. (DOCX 18 kb)Additional file 4:STROBE quality assessment. Table including information of the quality assessment conducted on all observational studies. (XLSX 16 kb)


Unconscious bias and explicit forms of discrimination continue to pervade academic institutions. Multicultural and diversity training activities have not been sufficient in making structural and social changes leading to equity, therefore, a new form of critical consciousness is needed to train diverse scientists with new research questions, methods, and perspectives. The purpose of this paper is to describe Building Infrastructure Leading to Diversity (BUILD); Promoting Opportunities for Diversity in Education and Research (PODER), which is an undergraduate biomedical research training program based on transformative framework rooted in Critical Race Theory (CRT).By employing a CRT-informed curriculum and training in BUILD PODER, students are empowered not only to gain access but also to thrive in graduate programs and beyond. Poder means “power” or “to be able to” in Spanish. Essentially, we are “building power” using students’ strengths and empowering them as learners. The new curriculum helps students understand institutional policies and practices that may prevent them from persisting in higher education, learn to become their own advocates, and successfully confront social barriers and instances of inequities and discrimination. To challenge these barriers and sustain campus changes in support of students, BUILD PODER works toward changing campus culture and research mentoring relationships. By joining with ongoing university structures such as the state university Graduation Initiative, we include CRT tenets into the campus dialogue and stimulate campus-wide discussions around institutional change. Strong ties with five community college partners also enrich BUILD PODER’s student body and strengthen mentor diversity. Preliminary evaluation data suggest that BUILD PODER’s program has enhanced the racial/ethnic consciousness of the campus community, is effective in encouraging more egalitarian and respectful faculty-student relationships, and is a rigorous program of biomedical research training that supports students as they achieve their goals.Biomedical research programs may benefit from a reanalysis of the fit between current training programs and student strengths. By incorporating the voices of talented youth, drawing upon their native strengths, we will generate a new science that links biomedical research to community health and social justice, generating progress toward health equity through a promising new generation of scholars. Poder means “power” or “to be able to” in Spanish. Essentially, we are “building power”—empowering students. The curriculum helps students understand institutional policies and practices that may prevent them from persisting in higher education, learn to become their own advocates, and successfully confront social barriers and instances of inequities and discrimination.California State University, Northridge’s BUILD PODER program , funded by the National Institutes of Health, is diversifying the biomedical workforce by reframing and redesigning institutional practices, undergraduate biomedical research training, and research mentoring approaches through the lens of Critical Race Theory (CRT) –3. In BUCritical Race Theory has its roots in the 1960s Civil Rights and 1970s Critical Legal Studies movements and “critically interrogate[s] how the law reproduces, reifies, and normalizes racism in society” . There aCritical Race Theory provides educators and researchers with a framework to challenge the racist historical and institutional roots of educational inequality that persist today –15. SociThrough the lens of CRT, BUILD PODER is working to interrupt the majoritarian narrative by building a community of biomedical scholars, students, faculty, and administrators equipped with the tools to develop more egalitarian, respectful structures and relationships in biomedical research and mentoring by addressing, for example, unconscious bias, White privilege, microaggressions, stereotype threat, structural racism, historical trauma, and the influence of racism on science. Through education and activities, students and mentors also better understand the intersectionality of race with gender, ability, sexual orientation, as marginalized groups –30. BUILhttp://www.cbecal.org/get-involved/toxic-tours/) [“CRT practice attends to the voice of the marginalized by placing it in social context, and translating personal pain into a social justice agenda at the direct practice level” . The pri-tours/) . The HeaOf particular concern are the many barriers, such as racism, to recruiting minorities into biomedical graduate programs  and optiDespite efforts to close the achievement gap, barriers for traditionally underrepresented groups (URGs) are reflected in: (1) the length of time to graduation ; (2) lacEven when they successfully negotiate graduate degrees, students of color frequently feel alienated , requireCalifornia State University, Northridge (CSUN) is one of 23 CSU campuses and, with 39,900 students, is a Minority Serving , a Hispanic Serving , and an Asian American Native American Pacific Islander Serving  Institution. CSUN has long been recognized by NSF’s Survey of Earned Doctorates as providing students with experiences and opportunities that put many of its STEM programs in the top 20 in the nation for matriculating undergraduates who go on to earn a doctorate in sciences, social sciences, and specifically in psychology (rated No. 1 among 529 comprehensive universities in recent years) . TherefoIn Table whole student, not just fill in gaps in their knowledge . While it was essential for students to acquire social and cultural capital needed to succeed in academia, it was equally important for students to recognize that they come from communities of cultural wealth [In order to increase the number of traditionally underserved students who pursue graduate degrees in the biomedical sciences, BUILD PODER was designed to focus on supporting and empowering the l wealth . ThroughSolórzano and Yosso  describeThroughout the year, discussions focus on issues of race, racism, sexism, and other forms of discrimination. Students are introduced to the research on gender and racial microaggressions , the infIn an invited talk at the Association for Psychological Sciences in 2015, psychologist Robert Sellers stressed the importance of diversity in science, but cautioned that scientists must not discount URGs’ unique viewpoints and experiences. He stated, “If we’re only training people to think like us, then we’ve lost our advantage.” Yosso’s cultural community wealth  builds oRecruitment efforts focus on the visibility of BUILD PODER through personal contact, digital, social, and traditional media  at CSUN, community college partner campuses, and in the community. Beginning early in the academic year, staff make classroom announcements and attend school-wide events. Partnerships with advisement offices, the Educational Opportunity Program (EOP), and CSUN’s public relations office are essential. BUILD PODER hosts information sessions in the Fall semester, followed by application workshops that help to increase the number and quality of complete applications. The online application system allows us to track students’ application progress, enabling us to contact students who haven’t completed their applications. Last, there is no better recruitment tool than the students. The first Wednesday of every month is BUILD PODER Wednesday, when all students and program staff proudly wear their program t-shirts.http://www.csun.edu/build-poder) to communicate with current and prospective students and faculty mentors and institutional partners. BUILD PODER has a “spotlight” section that highlights student accomplishments. The weekly e-Newsletter keeps the community up to date on upcoming events, and CSUN’s on-campus MIND screen (Matador Information Network Displays) televisions display current information about program events along with application information. BUILD PODER has also been featured twice in CSUN Today, a student operated e-magazine (http://csunshinetoday.csun.edu/education/22-million-awarded-to-csuns-build-poder-program/ and http://csunshinetoday.csun.edu/education/build-poder-welcomes-applicants-for-second-cohort-by-feb-5-deadline/).BUILD PODER uses its website  enhancing faculty research skills, (2) improving faculty mentoring competencies using the tenets of CRT, and (3) increasing campus-wide awareness and generating new practices around the tenets of CRT. When faculty research is stronger, students benefit from higher-quality research experiences, increased research infrastructure, and participation in publications and grant proposals , 80, 81.Incorporating the tenets of CRT into mentor training and competence, detailed below, opens up the consideration of structural racism as a barrier for students, faculty, universities, and science, and honors students’ experiential knowledge and motivation to generate social change, particularly in areas where health disparities exist , 82–85.BUILD PODER has initiated a gradual campus cultural transformation through a campaign of awareness, deconstruction, reconstruction, and praxis around racism . BUILD PFaculty members at comprehensive institutions, typically academically successful and holding greater privilege than their students, often have a view of academia that differs from that of their students –92. TraiUnderlying much of the chasm between faculty and students are implicit structural and interpersonal sources of bias. While we know that having experience with others who are culturally different can make one more predisposed to want to work further with culturally different people , 95–98, The application of CRT for faculty members starts with a 2-4 day, 16-h mentor training workshop that serves as a “soft” introduction to the theory and its application to biomedical research mentoring. In Year 1, faculty mentors learn to recognize their privilege and unconscious biases that lead them to fall prey to microaggressions and stereotype threat, to practice listening to students’ experiential knowledge and goals, and to engage in constructive dialogues about race, shown to increase mutual respect and understanding , 108. InWe commissioned a diversity and organizational change consulting firm who read our NIH BUILD proposal, read “Entering Mentoring” , and conColorblindness often translates into the superficial treatment of diversity through multiculturalism, a “race-neutral” approach to celebrating culture that ignores the structural and personal barriers that students of color face every day , 23, 110Traditional views of diversity and equality justify the status quo while the players take on roles of collusion: White faculty show trepidation in working with others who are different from themselves , 83, 93.Cultural and institutional change through a CRT lens in a historically Predominantly White Institution (PWI) requires long-term planning and problem-solving across units. With the goal of intentionally centering students, faculty, and research topics that are traditionally marginalized, BUILD PODER’s Health Equity Research and Education (HERE) center will provide a home base and resource center for health equity research and researchers. Our center, sustained by external funding from training and research grants, will coordinate with many campus offices and programs including workforce diversity, community welfare, ethnic studies departments, Education, EOP, the Civil Discourse and Social Justice group, Deaf Studies, Student and Faculty Affairs, Institutional Research, and existing research training programs. HERE will support and synthesize campus and community-based research in health equity and train newer researchers (students and faculty members) to conduct socially relevant, interdisciplinary research to ultimately move to R01 competencies among faculty members whose interest is in social justice and health equity. Figure The overarching goals of the HERE center are to (1) increase grant activity in the area of health equity, (2) increase interdisciplinary and collaborative research in health equity, (3) increase community engagement and collaboration around health equity using Community Based, Participatory Research (CBPR) and Participatory Action Research (PAR), (4) increase health equity in the San Fernando Valley region, and (5) provide a focal point for biomedical research by centralizing campus training and resources for students, faculty, and community members related to health equity research and training.Sharing the CRT framework of BUILD PODER, the leadership of HERE will be largely based on group consensus and will be built on recommendations from BUILD PODER’s Local Steering Committee, which includes two NIH support officials and two experts in CRT and program implementation as well as two CRT consultants who work on program sustainability , 115–117California State University, Northridge recently broke ground on “Research 1,” a new building, 10,000 square feet that will be occupied by two sets of cluster hires, one sponsored by BUILD PODER. In addition, Research 1 will serve as the physical home base for HERE students and researchers, BUILD PODER’s Health Equity Research and Education (HERE) center will house a student work space alongside a tutoring office, community college “transfer receptive” office, and resource center for undergraduate biomedical health equity research. HERE will also house three interdisciplinary cluster hires in health equity across the Colleges of Health and Human Development and Social and Behavioral Sciences. Several activities, highlighted in Fig. Three cluster faculty hires, followed by two additional faculty members within the next 3-5 years, will form a research group who will work on “Family Health and Disability Equity” (the cluster’s theme) by studying disparities in family-level resources, practices, and outcomes by racial/ethnic and social class status in the Los Angeles region. Engaging in this type of hiring will provide CSUN the opportunity to build upon existing strengths and spawn new areas of scholarship across campus by: enhancing the existing critical mass of faculty; promoting new and promising avenues of scholarship; meeting regional and national areas of need; growing interdisciplinary scholarship and collaboration; developing interdisciplinary curricula programs, and/or infrastructure to support student success; realizing institutional aspirations  and achieving campus priorities ; building community across the faculty and establishing collaboration as a value at CSUN; and serving as a mechanism for faculty retention and support for new faculty hires .www.csun.edu/faculty). The Scholarship tab on the App site is the home of this virtual network, which was created through partial funding from BUILD PODER. The overall goals of Scholarship are to create a stronger campus community, provide a platform for faculty to connect with fellow faculty, create more visibility for research projects, and encourage collaborative research. The key features include sections highlighting faculty research interests, projects, and resources, all searchable by other faculty, students, and the community.Building community among busy scholars is made easier through a newly created CSUN web platform, the “Faculty App” . To build community with students who are not on campus, community college students take part in bimonthly online meetings with PI Chavira and the Summer JumpStart Program, where high and consistent expectations are set for lab research with the goal of CSUN transfer. All Pipeline mentors participate in a four-hour CRT-based mentoring workshop. After struggling initially with student recruitment and building bridges between CSUN and campuses that are spread out over great geographic distances, we sought funds from a private foundation to recruit and support community college students. Trained at UCLA’s Center for Community College Partnerships, BUILD PODER’s new staff members are building relationships, starting newsletters, and participating in team-building activities across CSUN and Pipeline Partners.Research partnerships with local University of California campuses and Claremont Graduate University provide both practical  and emotional or psychosocial support  , 126. ReBUILD PODER is also building partnerships with local K-12 schools to support the early development of a research identity. McWilliam, Poronnik, & Taylor  have cleLocal site level evaluation for BUILD PODER is conducted in collaboration with the CSUN Center for Assessment, Research and Evaluation (CARE), the primary interface between CSUN activities and the Diversity Program Consortium (DPC) Coordination and Evaluation Center (CEC) at UCLA. CARE works to support BUILD PODER by coordinating evaluation activities at CSUN with those across the consortium, facilitating the collection of consortium-level data at CSUN, and conducting specific local site evaluation. Three core areas  are examined at the local site level, each with its own specific aims and detailed evaluation plan.The overarching goal of evaluation activities focusing on student training is to examine changes in diversity, research preparation, and career development among CSUN students in the biomedical sciences. As Community College Pipeline Partners are central to the BUILD PODER program, the integration of students from partner colleges is a key component of evaluation activities. Of particular interest for the evaluation are the ways that the BUILD PODER program improves student understanding and experience in biomedical research (e.g. through the JumpStart program), enhances knowledge of CRT and research ethics, and serves to build a community among participating students. Unique elements of the evaluation approach include examining student perceptions of their experience of microaggressions and stereotype threat, how these perceptions affect their relationships with mentors, their development of a research identity, and overall interest in science and scientific research.Student-focused evaluation activities are complemented by faculty development. The overall evaluation objective is to assess the implementation and success of BUILD PODER in the following areas: (1) increasing and expanding the number of faculty engaged in research; (2) expanding the number of available training opportunities for research development and culturally sensitive mentoring; (3) growing the number of collaborative research opportunities; and (4) enhancing the number and quality of research programs and grant proposals. Particular attention is given to evaluating how innovations developed by BUILD PODER  work to enhance faculty engagement in research and grantsmanship, and promote student professional development in the biomedical sciences.The focus of the evaluation emphasizes specific aims related to the oversight, institutional development, and sustainability of the BUILD PODER program. Evaluation activities also assess infrastructure development at CSUN, opportunities for virtual collaborations, and new curriculum advancements, as well as the augmentation of external research partnerships with Pipeline colleges. Of specific interest are the transformations in the CSUN institutional culture and concomitant policies that emerge as a result of the implementation of BUILD PODER. As a unique component of BUILD PODER, particular attention is given to assessing the impact of the incorporation of principles of CRT at the university level as a guiding framework for promoting an inclusive and culturally sensitive culture for student and faculty research and mentoring.Local site evaluation of the BUILD PODER program follows both ethnographic and quasi-experimental methods, and emphasizes both formative and summative evaluation. The specific evaluation methods vary depending on the aims of each core, and include: (1) pre- and post-test questionnaires; (2) analysis of existing data and documents; (3) individual and focus group interviews; and (4) ethnographic observations and virtual ethnographies. Formative evaluation activities utilize ethnographic observations and interviews to assess the quality and fidelity of implementation. Here, the CRT methodological framework is utilized to provide participants opportunities to express counter-stories that challenge dominant ideologies and to elicit multicultural affirmations. In order to assess summative outcomes, the evaluation of BUILD PODER employs pre- and post-test questionnaires as well as the analysis of existing data. Here, students and faculty are observed over time on domains related to research interest and engagement, professional research opportunities, mentor-mentee relationships, and experiences related to cultural bias and microaggressions.CSUN’s BUILD PODER is one of two BUILD sites that have a focus on issues of race and discrimination, and is the only site that integrates structural, personal, and cultural factors through CRT and understanding the value of students’ social capital including cultural, linguistic, familial, and resistive strengths. While it is a process, developing a campus culture of openness and understanding of racism and its consequences allows for the potential to move beyond practices that reify educational inequity by exchanging ideas and developing new practices that are less hierarchical, more respectful, and open to ideas generated by students who often come from communities that experience health disparities. Students, faculty members, and administrators have been exposed to and have interacted with CRT concepts including racial/ethnic microaggressions, power relationships, and implicit bias, and are working toward models of laboratory relationships that honor and implement ideas generated by students in conjunction with their faculty mentors.Awareness of factors contributing to low persistence among students from ethnic minority communities  has beenWe have built a community of support and help students secure supportive networks within and outside of the university. Students know that they have a “home base”  if they Whereas many undergraduate training programs take a deficit approach (focus on what students lack) in preparing students for graduate studies in the biomedical sciences, we acknowledge students’ strengths and we focus on strengthening both faculty mentors and students. Faculty mentors are trained to be culturally responsive, and students learn the skills to be successful in their fields through culturally competent training.There remain many challenges, including long-standing policies that reinforce inequities , well-established resistance to personal reflection about one’s potentially racist beliefs and actions, and the sheer complexity of activities and tracking a large number of students (more than 100 each year). Several institutional variables have been addressed through programmatic arrangements with advisement, financial aid, and other entities. We continue, through annual training and continuous reinforcement of CRT concepts, to develop a campus culture that is critical of racial/ethnic bias and works actively toward making a change in education as a whole and in biomedical research specifically. One of the biggest challenges is recruitment of students and faculty mentors. At CSUN and at the Pipeline Partner institutions, students from traditionally underserved communities are less likely to apply to undergraduate research training programs because of low self-efficacy and a lack of identification as “biomedical,” a “scientist,” or a “researcher.” At the Pipeline Partner institutions, we have encountered additional challenges such as fewer students meeting the eligibility criteria due to part-time enrollment status, low grades in core science and math courses, familial obligations, and full-time work outside of school. In contrast to CSUN, where we have more than 100 faculty research mentors, we have only 18 research mentors at the Pipeline Partner institutions, due to part-time adjunct status, high teaching load, or a lack of facilities at the institution to conduct research. To address this challenge, in 2016 we were awarded a grant from the Annenberg Foundation to hire two recruitment specialists who will be primarily at the Pipeline institutions working with student services staff, faculty, and students in order to increase the pool of applicants and help recruit more research faculty mentors at these institutions.The unique contributions of BUILD PODER lie in recognizing and working toward releasing structural constraints that influence personal goals by inculcating a sociological imagination , or the


Examining the role of modifiable barriers and facilitators is a necessary step toward developing effective implementation strategies. This study examines whether both general  and strategic (implementation climate and implementation leadership) organizational-level factors predict therapist-level determinants of implementation (knowledge of and attitudes toward evidence-based practices).Within the context of a system-wide effort to increase the use of evidence-based practices (EBPs) and recovery-oriented care, we conducted an observational, cross-sectional study of 19 child-serving agencies in the City of Philadelphia, including 23 sites, 130 therapists, 36 supervisors, and 22 executive administrators. Organizational variables included characteristics such as EBP initiative participation, program size, and proportion of independent contractor therapists; general factors such as organizational culture and climate  and transformational leadership (Multifactor Leadership Questionnaire); and strategic factors such as implementation climate  and implementation leadership . Therapist-level variables included demographics, attitudes toward EBPs , and knowledge of EBPs (Knowledge of Evidence-Based Services Questionnaire). We used linear mixed-effects regression models to estimate the associations between the predictor  and dependent (knowledge of and attitudes toward EBPs) variables.Several variables were associated with therapists’ knowledge of EBPs. Clinicians in organizations with more proficient cultures or higher levels of transformational leadership  had greater knowledge of EBPs; conversely, clinicians in organizations with more resistant cultures, more functional organizational climates, and implementation climates characterized by higher levels of financial reward for EBPs had less knowledge of EBPs. A number of organizational factors were associated with the therapists’ attitudes toward EBPs. For example, more engaged organizational cultures, implementation climates characterized by higher levels of educational support, and more proactive implementation leadership were all associated with more positive attitudes toward EBPs.This study provides evidence for the importance of both general and strategic organizational determinants as predictors of knowledge of and attitudes toward EBPs. The findings highlight the need for longitudinal and mixed-methods studies that examine the influence of organizational factors on implementation. There are a growing number of evidence-based practices (EBPs) for youth psychiatric disorders , 2, but While individual- and provider-level factors are widely acknowledged to be critical to effective implementation, the literature is still in a nascent state in two respects. First, many conceptual models and frameworks do not specify relationships among individual and organizational constructs. This limits our ability to understand how these factors coalesce to influence implementation success or failure and, hence, how implementation strategies , 21 shouSecond, while some of the more general organizational constructs  have a relatively long history and have been well studied in a variety of fields , 23, manOrganizational culture and climate have a relatively long history in organizational research . In the Implementation climate has been defined as employees’ shared perception that a specific innovation is expected, supported, and rewarded within their organization . Strong Effective leadership is essential for implementation success , 23 and Aarons and colleagues  have devKnowledge of EBPs is a precursor to implementation and is a key construct in some of the most commonly used implementation frameworks , 50. ForThe purpose of this study was to (1) assess the relationship between general and strategic organizational-level determinants and therapist-level determinants of implementation and (2) to determine whether strategic organizational-level determinants predict individual-level determinants after controlling for general organizational-level determinants that are more firmly established in the implementation literature. We hypothesized that more positive general organizational determinants  would be associated with increased therapist knowledge of and more positive attitudes toward EBPs, because they are characterized by (1) more proficient organizational cultures in which therapists are expected to have up-to-date knowledge of best practices and they are less resistant to change ; (2) orgThis study was conducted in partnership with Philadelphia’s Department of Behavioral Health and Intellectual disAbility Services (DBHIDS), a large, publicly funded urban system that pays for mental health and substance abuse services through a network of more than 250 providers. In partnership with Community Behavioral Health, a not-for-profit 501(c)(3) corporation contracted by the City of Philadelphia, they provide behavioral health coverage to more than 500,000 Medicaid-enrolled individuals . Since 2More than 100 community mental health agencies in Philadelphia provide outpatient services for children and youth . Purposive sampling  was usedThe institutional review boards in the City of Philadelphia and at the University of Pennsylvania approved all study procedures. The executive administrator at each of the 23 organizations was asked to participate in the study. They completed their questionnaires using REDCap, a secure Web-based application that supports online data collection . For supDemographics were assessed using the Therapist Background Questionnaire .Three organizational characteristics were measured: number of therapists, proportion of staff that were independent contractors, and the total number of years each organization participated in each of the city-sponsored EBP initiatives . Data regarding the number of therapists and proportion of staff that were independent contractors was collected from organizational leaders, and data regarding EBP initiative participation was obtained from Community Behavioral Health and DBHIDS leadership. All three of these characteristics can be considered proxies for the amount of financial and human capital that may be available for EBP efforts. Financial difficulties  have ledT-scores, in which a score of 50 represents the mean and the standard deviation is 10. These T-scores are based upon a normed sample of 100 community mental health clinics in the USA [Organizational culture and climate were measured from the perspectives of therapists, supervisors, and executive administrators using the Organizational Social Context Measurement System (OSC) . The OSC the USA . The OSC the USA , and the the USA , 69.Implementation climate was measured from the perspective of therapists, supervisors, and executive administrators with the Implementation Climate Scale (ICS) . The ICSTransformational leadership was measured from the perspective of therapists who rated their direct supervisor using the Multifactor Leadership Questionnaire (MLQ 5X Short) . The MLQImplementation leadership was measured from the perspective of therapists who rated their direct supervisor with the Implementation Leadership Scale (ILS) . The ILSTherapist knowledge of EBPs was measured using the Knowledge of Evidence-Based Services Questionnaire (KEBSQ) , a 40-itTherapist attitudes toward EBPs were assessed using the Evidence-Based Practice Attitudes Scale (EBPAS) , a 15-itOrganizational scores are constructed by aggregating individual responses within the organization; however, this is only meaningful if there is sufficient agreement within the organizational unit. We used mean within-group correlation statistics to determine agreement , 74. TheAnalyses were conducted using PROC MIXED in SAS statistical software, version 9.0 . We produced six linear mixed-effects regression models to determine the associations between the predictor variables  and dependent variables (knowledge of EBPs and attitudes toward EBPs). All models included random intercepts for organization to account for nesting of therapists within organizations and fixed effects for individual demographic and organizational factors. Demographic factors included age, sex, and years of clinical experience. Organizational characteristics included program size (number of therapists), ratio of independent contractor therapists, organizational culture , organizational climate , implementation climate , transformational leadership , and implementation leadership . The six dependent variables included knowledge of evidence-based services (KEBSQ) and attitudes toward EBPs .Demographic information for the participating therapists is detailed in Table Table Table Both strategic organizational factors (implementation climate and implementation leadership) were predictive of attitudes toward EBPs. Implementation climates characterized by higher levels of educational support were positively associated with higher ratings for requirements, appeal, and total attitudes toward EBPs, and negatively associated with divergence. Implementation climates that provided more monetary or tangible rewards for EBPs were associated with higher ratings for divergence. Selection for openness (implementation climate) was positively associated with appeal of EBPs. Proactive implementation leadership was associated with higher levels of appeal and total attitudes toward EBPs. Knowledgeable implementation leadership was associated with lower levels of perceived divergence. Finally, perseverant implementation leadership was associated with lower ratings of attitudes toward EBPs .This observational, cross-sectional study contributes to our understanding of how organizational factors are associated with clinician-level determinants of implementation in behavioral health , 56, 76.More proficient organizational cultures were associated with higher knowledge of EBPs, which is consistent with the literature that suggests proficient cultures are characterized by having up-to-date knowledge of best practices , 37. ConOrganizational climates that were more engaged were associated with higher overall attitudes toward EBPs. Engaged climates are characterized by therapists’ perceptions that they are able to personally accomplish worthwhile things, remain personally involved in their work, and maintain concern for their clients . Thus, oTransformational leadership  was associated with higher levels of knowledge of EBPs and attitudes toward EBPs as inspirational motivation was associated with less perceived divergence between EBPs and usual practice. Transformational leaders inspire others and provide them a vision for what can be accomplished through extra personal effort and also encourage development and changes in mission that may lead therapists to have greater willingness to expend extra effort to learn new EBPs and push themselves to achieve more professionally . TransfoImplementation climates that provided more educational support were associated with more positive attitudes toward EBPs, including higher ratings for being likely to adopt EBPs if they were required, higher ratings for appeal, lower levels of perceived divergence between EBPs and usual practice, and more positive overall attitudes toward EBPs. The educational support dimension of the ICS includes items about support for conferences, workshops, seminars, EBP trainings, training materials, and journals . EnablinFinally, more proactive implementation leadership was associated with greater appeal and more positive total EBPAS scores, and implementation leadership characterized as more knowledgeable was associated with less perceived divergence between EBPs and routine practice. Leaders that are proactive and have up-to-date knowledge of EBPs and are able to answer staff questions about them are likely to encourage therapists to view EBPs as a potentially feasible complement to their practice and dissuade them from thinking that EBPs are irrelevant or invalid treatment options. Perseverant implementation leadership was associated with lower willingness to adopt EBPs if required, less appeal of EBPs, and poorer overall attitudes toward EBPs. While it is difficult to interpret this finding, it may be that some leaders are more perseverant as an adaptive response to working in agencies comprised of therapists with poorer attitudes toward EBPs. It is also possible that the perseverance of leaders is being interpreted negatively by therapists, as they may perceive that leaders are being too dogmatic in attempting to implement EBPs in the face of all of the challenges associated with EBP implementation in large publicly funded behavioral health systems and that they may not be listening to or validating their concerns .These findings should be viewed in light of several limitations. First, while we obtained a relatively high response rate (~50% of therapists employed at the 23 agencies), we did not have 100% participation and it is possible that nonparticipants’ views of their practice context differed from participants’ views. Second, the cross-sectional data preclude our ability to make causal statements about how the organizational context influences attitudes toward and knowledge of EBPs over time. Third, the organizations and therapists participating in this study were implementing a range of treatments, not all of which would be considered evidence-based. Variation in exposure to EBPs may have impacted their attitudes toward and knowledge of EBPs; however, the number of years the organizations participated in EBP initiatives was not predictive of either attitudes toward or knowledge of EBPs. Fourth, given the observational nature of this study and the inherent variation in the types of treatments implemented in community settings, we were unable to obtain objective ratings of fidelity. The variation in treatments implemented also precluded our ability to use innovation-specific versions of the ICS or the EBPAS, which may have greater predictive validity , 44.This study suggests several important directions for the field. Improving our understanding of context will require continued efforts to develop and refine pragmatic measures of implementation determinants that would be relevant to behavioral health and health-care settings , 79. SomThis study provides further evidence that both general and strategic organizational factors are important determinants to consider. While both general and strategic factors predicted knowledge of and attitudes toward EBPs, it is possible that the strategic organizational factors could be more feasible targets for change, as it may be somewhat easier to promote the improvement in implementation climate and leadership as compared to changing more durable general organizational determinants such as organizational culture and climate, which are expensive and time-consuming to address . However


We identified Usutu virus (USUV) RNA in 6 pools of mosquitoes trapped in northern Israel during 2014–2015. These Israeli strains were most similar to strains identified in Senegal and Germany, which further elucidates common ancestry and evolutionary dynamics of USUV. Our findings suggest that human infection with USUV might occur in Israel. Culex spp. mosquitoes (Usutu virus (USUV) is a vectorborne flavivirus first isolated in South Africa in 1959  gene as described (During 2014–2015, a total of 53,890 mosquitoes were trapped and grouped into 1,471 pools of escribed  and beloescribed .Cx. neavei mosquitoes in 2007 in Senegal (We then performed amplification of an 845-nt sequence containing part of the envelope, membrane, and premembrane genes of USUV as described ( Senegal , panel AWe then performed phylogenetic analysis of part of the NS5 gene because a previous study showed that this sequence exhibits a phylogenetic signal similar to the complete genome , panel BDespite its identification in 1959, USUV was not considered a potential public health concern until the early 2000s, when the first large USUV outbreak in birds occurred in Austria (Cx. pipiens and Cx. perexigus mosquitoes in Spain (Cx. pipiens and Cx. torrentium mosquitoes in Germany (Ae. albopictus and Cx. pipiens mosquitoes in Italy (Cx. perexigus, Cx. pipiens, and Ae. albopictus mosquitoes also suggests that USUV is transmitted by these 3 mosquito species in Israel.USUV RNA has been detected primarily in Recently, reconstruction of the evolutionary history and dispersal of USUV has identified 6 distinct lineages of USUV. Nevertheless, Engel et al. concluded that limited numbers of USUV isolates from Africa and lack of data for countries located between Africa and Europe might obscure additional spatial movements (Our phylogenetic analysis of the NS5 gene  showed tBecause Israel is located on a bird migration path between Africa and Eurasia, USUV strains isolated in Germany, which are part of the Europe 5 and Africa 3 lineages, might have arrived from Africa through Israel, thus explaining the relative similarity of the strains in Israel to both lineages. Identification of more isolates from the Middle East and in-depth sequence analysis are needed to examine the geographic spread of the virus and further decipher its evolutionary history.Our results showed that all 6 USUV-positive pools were captured in 3 mosquito species in northern Israel . BecauseGiven the history of flaviviruses that were responsible for major outbreaks worldwide after decades of silent circulation, such as WNV and Zika virus, the accumulating evidence of increased activity of USUV in Europe is alarming. Therefore, investigation of USUV in mosquitoes in Israel is essential, not only because of public health concerns but also because of a need to understand the kinetics and penetration routes of USUV from Africa into Europe, Asia, and the Middle East.


A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network. However, there are major challenges that impact the development of novel therapies, including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response. A notable development is the creation of collaborative ecosystems that include patients, clinicians, basic and translational researchers, foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent, reverse or delay the progression of neurodegenerative proteinopathies. Many neurodegenerative diseases involve the misfolding and aggregation of specific proteins into abnormal, toxic species. Therapeutic targeting of protein misfolding has generated unique challenges for drug discovery and development for several reasons, including 1) the dynamic nature of the protein species involved, 2) uncertainty about which forms of a given disease protein  are primarily responsible for cellular toxicity, 3) our still limited understanding about which components of the cellular proteostatic machinery these disease proteins interact with and 4) lack of well-validated biomarkers for clinical trials. However, as we continue to gain knowledge of disease mechanisms, improve our abilities to model disease states in vitro and in vivo, and identify new biomarkers, there is increasing optimism that we will discover novel therapeutics that prevent, reverse, or delay the progression of neurodegenerative diseases. In concert with the scientific advances in the past several decades, the field of neurodegenerative disease research is undergoing significant change with respect to how various stakeholders engage each other and share information with the entire community. Increasing collaboration between scientists from the pharmaceutical industry disease foundations, academic researchers, contract research organizations, and patient advocacy group, and increasing communication between groups studying different diseases, has spurred promising initiatives in basic, translational, and clinical research in neurodegenerative disease.There are multiple steps in the production and processing of disease proteins that could be targeted therapeutically, from initial synthesis to degradation and extracellular clearance Fig. . This reMisfolded proteins exist in cells together with unfolded, intermediately folded, and correctly folded species . In healOnce formed, higher order amyloid aggregates are highly resistant to degradation. Proteasomes can degrade only single chain polypeptides, and also require the proteins to be partially or fully (in the case of proteasomes) unfolded . In addiUnder conditions of proteotoxic stress, cellular aging, or the presence of disease mutations, proteins can escape a cell’s quality control system and begin to aggregate into non-native structures, which range from oligomers and amorphous assemblies to highly ordered amyloid fibrils and plaques.Cells are normally faced with a continuous stream of misfolded proteins arising from mistakes in biogenesis, disease-causing mutations, and physiological stressors  involve large-scale rebalancing of the proteostatic network via transcriptional regulation of both chaperones  and non-chaperone proteins , it was originally thought that fibrils and plaques were the pathogenic species in Alzheimer’s disease, but more recent studies point to aggregation intermediates (oligomers and soluble protofibrils) as the primary culprits; similar findings have emerged with respect to different species of α-synuclein in Parkinson’s disease , 48. TheIdentifying key toxic species of misfolded proteins has been challenged the inability of conventional biochemical analytic methods to detect and characterize intermediate species. For example, denaturing gel electrophoresis (SDS-PAGE) has been shown to alter the oligomerization state of Aβ42 oligomers . RecentlIn cases where the relative pathogenicity of various misfolded protein species is unknown, one strategy would be to intervene therapeutically as far upstream as possible in the protein synthesis pathway: i.e., at the level of protein translation, cleavage, or post-translational modification. In theory, targeting early steps in the processing pathway would provide the highest degree of therapeutic specificity and eliminate toxic gains or losses of function caused by misfolded or aggregated forms of the protein, while preventing the propagation of abnormal folding and aggregation. Protein cleavage and post-translational modification targets are being actively explored for Aβ using Beta Amyloid Cleaving Enzyme (BACE) inhibitors  and for tau using inhibitors of tau phosphorylation  and acetylation –60.Chaperones are another possible target class for therapeutic intervention in protein misfolding disease states. As chaperones are involved in all aspects of proteostasis, they offer potential therapeutic entry points to each step in the processing of a pathogenic protein. There are over 200 different chaperone proteins expressed in the mammalian brain , and difOne approach to therapeutically targeting the chaperone system has been to develop small molecule inhibitors or activators of specific chaperones. Among chaperones relevant to neurodegeneration, Hsp70 and Hsp90 have been the most intensely studied. Hsp70 and Hsp90 have opposing effects on client protein stability: Hsp70 promotes their degradation via the UPS system, whereas Hsp90 stabilizes client proteins and inhibits their ubiquitination. The activities of Hsp90 and Hsp70 are tightly linked via HSF1. Hsp90 inhibitors typically activate HSF1, which in turn induces Hsp70 . A varieC. elegans model of PD [A second approach to developing chaperone-based therapeutics has been through protein engineering. For example, it was discovered that the yeast disaggregate Hsp104 has the ability to dissolve in vitro fibrils formed from a variety of neurodegenerative disease proteins, including tau, polyglutamine, Aβ42, α-synuclein and prion protein , 76. Howel of PD . Other cel of PD , and metel of PD .Defects in both the UPS and autophagy pathways of protein degradation are often seen in neurodegenerative diseases , 80. ForA number of small molecules have been identified that upregulate components of the UPS, promote the degradation of disease proteins and in vitro, and (in some cases) have neuroprotective effects on cultured cells –86, but Inhibition of the mammalian target of rapamycin (mTOR) pathway has proven to be an exceptionally effective approach for stimulating the degradation of neurodegenerative disease proteins. mTOR, a serine/threonine kinase, is a signaling nexus that collects information about ambient levels of resources necessary for cell growth  and up- or downregulates protein synthesis and degradation accordingly. When growth conditions are favorable, mTOR inhibits autophagy by inhibiting the ULK1 complex, which is required for the biogenesis of autophagosomes. Thus, mTOR inhibitors typically have the net effect of stimulating autophagy , 88.Rapamycin and other mTOR inhibitors increase the clearance of abnormal protein aggregates and slow neurodegeneration in both cell and animal models of a variety of neurodegenerative diseases, including AD, PD, spinocerebellar ataxia type 3, and frontotemporal dementia , 88. In Several mTOR-dependent activators of autophagy, including the natural compounds curcurmin and resveratrol, are currently in clinical trials for treating neurodegenerative diseases. However, mTOR is a multifarious protein that regulates many cellular processes in addition to protein degradation, and in clinical trials to date wmTOR inhibitors have caused unpredictable and undesirable side effects. Autophagy can be stimulated mTOR-independent mechanisms , 87, 88,One of the best-explored examples of targeting clearance of misfolded proteins has been the use of antibodies to promote clearance of Aβ. These antibodies are thought to operate by either or both of two mechanisms: 1) by penetrating the blood brain barrier (BBB) to bind Aβ in the extracellular space, and 2) through a”peripheral sink” effect . Almost Current challenges in the use of Aβ antibodies include low rates of BBB penetration , nonspecThe ability of the cell’s proteostatic machinery to counter proteotoxic stressors deteriorates with age, and is further compromised by mutations and other disease conditions that lead to the accumulation of misfolded proteins . Thus, aAgents targeting HSF1 or other master regulators of the proteostatic network have the advantages of being fast-acting and relatively agnostic to the identities of the misfolded proteins involved in a given neurodegenerative disease and to their mechanisms of aggregation and toxicity. The effects of such drugs are hard to predict, however. For example, the induction of the heat shock response actually exacerbates Htt IB formation in a cellular model of HD . In addiThe misfolded protein neuropathies have proven an exceptionally challenging arena for therapeutics development. Promising candidates for Alzheimer’s disease, Parkinson’s disease, ALS, and Huntington’s disease have been identified in preclinical studies, but very few have shown significant benefits in clinical trials  and the biochemical properties of misfolded disease protein aggregates . A potenFinally, there is a need for translatable biomarkers that robustly track the progression and severity of the disease for successful clinical trial. One approach has been to measure amounts of soluble disease protein in the cerebrospinal fluid (CSF). When analyzing soluble proteins, the stability and kinetics of protein turnover in the CSF must be established, along with inter- and intra-subject variability. A challenge with the use of soluble proteins as CSF biomarkers is their low concentrations in the CSF, which in turn produces a low signal-to-noise ratio. A new approach has been to study other components of the CSF, such as exosomes. Exosomes are released by most cell types, and carry cargoes of proteins that include misfolded disease proteins . For chaMolecular imaging approaches  are an alternate approach to assessing target distribution and engagement. Currently, direct imaging of neurodegenerative disease proteins in vivo is possible in humans only for amyloid and tau –125. MosA key issue that has arisen with respect to translatable biomarkers is lack of correlation between levels of disease proteins and functional outcomes in rodent models. For example, unlike humans, mouse AD models and some mouse HD models do not show neuronal cell death. However, even models that don’t show cell death do typically show neuronal dysfunction and synaptic loss. Imaging ligands that demonstrate synaptic loss are now being developed in humans, and could be reverse-translated for use in rodent studies . AlternaUntil recently, drug discovery was the almost exclusive domain of biotechnology and pharmaceutical companies. Today, a new model for drug discovery has evolved, spurred in large part by initiatives led by patient advocacy groups, philanthropic organizations, the National Institutes of Health and other international funding agencies. This new model involves coordinated collaborations between academia, industry, private foundations, and government funding agencies, and incorporates patients and caregivers as key collaborators, knowledge resources, and decision-makers. Private foundations are increasingly taking on leadership roles that used to be handled primarily by government agencies, including the facilitation and scientific management of focused research initiatives, large-scale research consortia, and partnerships between academia, industry, and CROs.Team approaches are particularly critical for the proteinopathies because of the heterogeneity and/or rarity of these conditions and the difficulty of recruiting sufficiently large patient cohorts for clinical trials for genetic disease. Patient advocacy groups and foundations are now playing critical roles in forcing some degree of standardization and scientific rigor, and providing critical natural history data for disease progression markers. Examples of such efforts include the Michael J. Fox Foundation Parkinson’s Progression Markers Initiative, the Target ALS drug discovery program, the Alzheimer’s disease Drug Discovery Foundation Access program, and the CHDI Foundation Preclinical Research program. Another key role for both governmental agencies and private foundations in supporting collaborations is through the development of public databases and “knowledge centers,” such as the National Alzheimer’s Coordinating Center and the Academic Drug Discovery Consortium. Recent national and international government initiatives supporting early drug discovery include the NIH Blueprint Neurotherapeutics Network and the European Innovative Medicines Initiative.There is active research ongoing to uncover the mechanisms by which disease-associated proteins misfold, aggregate, and cause cellular toxicity. Continued progress in our ability to interrogate amyloid-forming proteins and their interactions with other cellular proteins provide confidence that novel therapies will be identified for multiple disease states. Therapeutic options now being explored include targeting misfolded protein-chaperone interactions at various points in the proteostatic pathway, promoting protein clearance, and large-scale rebalancing of proteostatic network. However, the identification and in vivo validation of new therapeutic compounds is impeded by the shortage of known disease drivers and the lack of reliable biomarkers for monitoring therapeutic responses in relevant animal models. However, the increase in cooperative research and collaboration among the drug discovery community  is a positive shift that can help accelerate the identification of novel therapeutic modalities.


Persons affected by migration require health systems that are responsive and adaptable to the needs of both disadvantaged migrants and non-migrant populations. The objective of this study is to support health systems for populations affected by migration. Materials and Methods: An international Delphi consensus process was used to identify policy approaches to improve health systems for populations affected by migration. Participants were leading migrant health experts from Americas, Europe, Middle East, Asia, and Australasia. We calculated average ranking scores and qualitatively analyzed open-ended questions. Results: Participants identified the following key areas as priorities for policy development: health inequities, system discrimination, migrant related health data, disadvantaged migrant sub-groups, and considerations for disadvantaged non-migrant populations. Highly ranked items to improve health systems were: Health Equity Impact Assessment, evidence based guidelines, and the International Organization for Migration annual reports. Discussion: Policy makers need tools, data and resources to address health systems challenges. Policies need to avoid preventable deaths of migrants and barriers to basic health services. Modern populations are rarely homogenous, and the International Organization for Migration (IOM) reports global international migration is expected to double from 232 million to more than 400 million by 2050 [In 2015, more than 1.2 million asylum seekers and other migrants arrived in Europe in a short period of time and thousands more died in transit. The “European migrant crisis” led to a call for humanitarian action and a World Health Organization (WHO) call for responsive health systems around the world. The WHO responsiveness framework’s aims help populations equitably meet core social goals and international human rights. Populations also expect the health system to treat people with dignity. Within this framework, health system responsiveness was given the formal definition of “the ability of the health system to meet the population’s legitimate expectations regarding their interaction with the health system, apart from expectations for improvements in health or wealth”  may unintentionally cause unexpected stress to local health systems. Health systems may require interpreter services and additional service capacity, and migrants may need special health coverage ,3. MigraTraditionally, most political jurisdictions have not considered mass migration in their health system planning ,7. In soDecision makers are often faced with competing challenges, limited knowledge and limited financial resources. Efforts to prioritize policy challenges and the transfer of knowledge can improve health systems . The objA scoping literature review  and an iwww.surveymonkey.net). Each subsequent phase provided information to the participants regarding the stage of the Delphi consensus, emerging results and the priority setting criteria. This study received ethics approval from The Ottawa Health Science Network Research Ethics Board (OHSN-REB) and Bruyère Research Ethics Board (#M16-15-031). We conducted a Delphi consensus process to set priorities for building responsive health systems for refugees, other migrants and disadvantaged persons affected by migration. For the purposes of this paper, local disadvantaged populations are defined by low-socioeconomic status, disability and/or advanced age. This online consensus process involved a series of three phases conducted between 16 December 2015 and 24 May 2016. All three phases used Survey Monkey software  responded  belonging to a subgroup of migrants at risk for health inequities; (2) those subjected to political and system exclusions; (3) local members of the receiving communities facing competition due to mass migrations; and (4) Intersectionality ) e expert . Summaries of responses describing disadvantaged populations, awareness and use of practice-based tools and resources are provided in Out of the nine resources listed, the majority of experts were aware of (86%) and reported using (59%) the International Organization for Migration Annual Reports and other supporting publications see . Figure Phase 2: The results for the second phase identified key challenges to developing and implementing Responsive health system policies. The response rate for this phase was 83%. The top ranked priority challenges for developing responsive health system policies were: health inequities, the pressured policy process in migrant related initiatives, the reduced communication and participation due to limited language proficiency, and the challenges of engaging migrants as priorities to address for responsive health system policy development .Participants identified International Organization of Migration Health Equity Impact Assessment (HEIA) , WHO essPressured policy process was ranked as one of the most important health system issues to address. WHO and other organizations have used this point to push for responsive health systems before a crisis begins to mitigate population harms (WHO as above in intro). Rapid changes in the profile of migrants, politics, and limited resources challenge health system responsiveness. Without foresight, both low income migrants and non-migrants living in the receiving communities may suffer from inadequate systems. Integrating the HEIA tool within health system policy planning could support more equitable health service provision and strengthen the overall healthcare system ,17,18,19Health equity was identified as a policy priority for responsive health systems ,19. OfteEngaging migrant communities was identified as a key policy challenge. To ensure the engagement of migrants and other disadvantaged communities, countries need to support provision of culturally sensitive health systems to help empower migrants that in turn will increase their involvement. Further, governments need to prioritize data collection on disadvantaged communities, including migrants, to ensure a more holistic understanding of health.The international interdisciplinary stakeholder from 13 countries and showed a good response rate and completion rate (≥80%). This study has contributed to building shared vocabulary and processes that can be used at international migrant policy meetings and subsequent implementation of emerging recommendations. Overall, there was not a high number of participants. Notably, there was a limited number of experts from Africa, South East Asia, and South Asia. Participants did not include recent refugees, other migrants and people affected by migration. The Delphi required experts to communicate in English. A few experts found the wording/nomenclature of policy process questions complicated and difficult to understand. Studies from across the EU demonstrate considerable, but varied, health inequities between migrants and non-migrants . There iMigrant have overburdened the health systems of Europe, causing fundamental deficiencies in the infrastructure, guidelines, referral mechanisms, responsive funding and resources, preparedness and staff support . ConditiThe results of this Delphi consensus highlight some of the unique heath system needs that result from migration. Specifically, the processes identified aim to explicitly and systematically incorporate migrant needs into responsive health systems, to avoid crisis and ensure non-discrimination and equal entitlement to health services. Leading policy initiatives included the Health Equity Impact Assessment, WHO Essential Drug List, evidence based migrant health guidelines and the International Organization for Migration annual reports. All are equipped to help address inequities, racism and discrimination as well as addressing unique clinical needs. Responsive health systems need migrant engagement and migrant relevant program and policy development.