Borrelia burgdorferi sensu lato-infected ticks has increased in a NRW nature reserve. The literature suggests increasing age and male sex as risk factors for seropositivity, whereas the influence of socioeconomic status is controversial. Thus, we aimed to determine regional seropositivity for Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) and its risk factors in the Rhineland Study population in Bonn, NRW, and to compare it with previous surveys to evaluate potential effects of climate change.Lyme borreliosis is the most prevalent vector-borne disease in Europe, and numbers might increase due to climate change. However, borreliosis is not notifiable in North Rhine-Westphalia (NRW), Germany. Hence, little is known about the current human seroprevalence in NRW. However, the proportion of B. burgdorferi s.l. using a two-step algorithm combining enzyme-linked immunosorbent assay tests and line immunoblots. We calculated the odds of being classified as IgG or IgM positive as a function of age, sex, and educational level using binomial logistic regression models. We applied varying seropositivity classifications and weights considering age, sex and education to compensate for differences between the sample and regional population characteristics.We assessed seropositivity in 2865 Rhineland Study participants by determining immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies for B. burgdorferi s.l. were present in 2.4% and IgM antibodies in 0.6% of the participants . The likelihood of IgG seropositivity increased by 3.0%  per 1 year increase in age. Men had 1.65 times the odds for IgG seropositivity as women (95% CI 1.01–2.73), and highly educated participants had 1.83 times the odds (95% CI 1.10–3.14) as participants with an intermediate level of education. We found no statistically significant link between age, sex, or education and IgM seropositivity. Our weighted and age-standardized IgG seroprevalence was comparable to the preceding serosurvey German Health Interview and Examination Survey for Adults (DEGS) for NRW.IgG antibodies for B. burgdorferi s.l. seropositivity remained constant over the past decade in this regional German population.We confirmed that increasing age and male sex are associated with increased odds for IgG seropositivity and provide evidence for increased seropositivity in the highly educated group.  Lyme borreliosis is the most prevalent tick-borne disease in Europe . From 20Borrelia burgdorferi sensu lato (B. burgdorferi s.l.), the causal agent of Lyme borreliosis . The antigens used in the ELISA are a mixture of the B. afzelii strain Pko, the B. garinii strain PBr and the B. burgdorferi strain ZS7. The ELISA testing procedure was fully automated . Secondly, the presence of detected antibodies in positive and borderline samples was verified  by line immunoblots with a test sensitivity of > 99.9% and specificity of 98% . The line immunoblots considered the antigens OpsC (p23) from B. afzelii, VlsE recombinant from B. burgdorferi B31, p39 (BmpA) recombinant from B. afzelii PKo, DbpA (Pko) and DbpA  from B. bavariensis PBi and B. garinii PBr, p58 (OppA-2) recombinant from B. bavariensis PBi, p83/100 recombinant from B. afzelii PKo, and EBV VCA-gp125 (affinity-purified) for exclusion diagnostics. The classification of IgG and IgM antibodies considered Virotech units (VU), an arbitrary antibody quantification scale for ELISA, as follows: negative: VU < 9, borderline: VU >  = 9 and VU <  = 11, positive: VU > 11. Finally, all generated data were imported to LabImage® LA Software [Kapelan Bio-Imaging Solutions] to detect, combine and interpret the immunoblots. A medical-technical assistant conducted the technical verification, and a medical doctor for microbiology, virology and infectious disease epidemiology validated the results. In our primary analysis, we classified all subjects with either positive or borderline ELISA and subsequent positive line immunoblot as seropositive and all other combinations as non-seropositive. We performed two binomial logistic regression models to calculate the odds of being classified as IgG-positive or IgM-positive as a function of age, sex and educational level.A DIN EN ISO [German Institute for Standardization/European standard/International Organization for Standardization] 15189-accredited medical laboratory conducted the antibody analysis on the sera with a two-step algorithm according to MIQ 12  . The comWe classified educational level according to the International Standard Classification of Education (ISCED) 2011 as low (completed lower secondary education or below), middle  and high  as a proxy for SES.In sensitivity analyses, we investigated whether age, sex and educational level were associated with IgG and IgM VU, the original ELISA quantification scales without modification and regardless of serostatus, running two linear regression models with age, sex and education as predictors. For this analysis, we present unstandardized regression coefficients. Furthermore, we ran two ordinal logistic regression models with negative, borderline and positive IgG and IgM serostatus as ordinal outcome and age, sex and education as predictors.www.destatis.de [Finally, to compare our seroprevalence results with previous studies from approximately the same region, such as the DEGS serosurvey , we appltatis.de ). To comtatis.de , we weigtatis.de , 42.We carried out all analyses in RStudio . We used the glm function of the stats package with a logit-link for the logistic regression models and the lm function of the stats package for the linear regression models . For theOf the 2888 participants, serostatus could be determined for all but one participant, and information on educational level was available for all but 22 participants, resulting in 2865 participants for analysis Table . The parFigure n = 69) were classified as IgG-positive, 0.6% (n = 18) as IgM-positive and 0.1% (n = 3) as both IgG- and IgM-positive. Thus, we detected antibodies for B. burgdorferi s.l. in 2.9% of the participants. The relative frequencies for IgG seropositivity were higher in men than in women (3.2% of men versus 1.8% of women) and frequencies were comparable between the sexes for IgM seropositivity (0.7% of women and 0.6% of men). When considering the relative frequencies of ELISA-seropositive samples without immunoblot confirmation, seropositivity was higher for both IgG (6.8% in ELISA-only classification versus 2.4%) and IgM (1.0% versus 0.6%). When we applied the algorithm used in DEGS and BGS98 [Table nd BGS98 , 4.8% weThe median of the VU for the entire sample was 4.3 (interquartile range (IQR): 4.1) for IgG and 1.6 (IQR:1.9) for IgM. For the seropositive participants, the median was 29.1 (IQR: 14.56) for IgG and 13.85 for IgM (IQR: 6.6).The odds of being classified as IgG-positive increased by 3% 95% CI 1.5–5.2%) per 1 year increase in age  Table , we founB. burgdorferi s.l., applying a stringent classification scheme, were 2.4% for IgG, 0.6% for IgM, and 0.1% for both IgG and IgM antibodies. We demonstrated that varying classification algorithms found in the literature for seropositivity led to differences in seroprevalence. However, using identical classification as BGS98 and DEGS, our weighted and additionally age-standardized seroprevalence values were within the confidence intervals of the seroprevalence values previously reported for NRW [B. burgdorferi s.l. in light of climate change, despite reported changes in tick distribution and proportion of infection with Borrelia in one region in NRW [The weighted seroprevalence values for antibodies for  for NRW . Hence, n in NRW , 27.For IgG seropositivity, we found a statistically significant impact of age, sex and educational level, while for IgM, we found no statistical link between age, sex or education and seropositivity, the latter possibly due to the small proportion of IgM-positive individuals.As a use case, this study provides, therefore, valuable and detailed information for a region for which data on ticks are worrying from a public health perspective and data on Lyme borreliosis are largely missing. Further, our results highlight the essential requirement for comparable classifications, as they evidently influence seropositivity results and, therefore, must be identical if seropositivity results are to be compared across studies. Large differences between different ELISA systems have already been demonstrated  and emphIn our main analysis, we confirmed the general effect of age for IgG seropositivity that has been reported in previous studies , 48. IgGB. burgdorferi s.l. The negative association between age and IgM units could suggest that the IgM-related immune response decreases with age [From the IgG unit data, we find that IgG units were on average higher in older participants, which fits to the above-discussed explanation of cumulative lifetime exposure to with age . Howeverwith age .Borrelia seropositivity [N = 1213), the lower number of participants per category may have limited the statistical power to detect an existing association. We found participants with a higher level of education to have higher odds for IgG seropositivity than individuals with an intermediate level of education. A potential explanation for our finding is differing life circumstances, including the living environment, leisure activities and access to green spaces and nature, resulting in differences in tick exposure [Previous studies discussed a potential interplay between SES, time spent outside  and sitivity –39; in tsitivity . We are sitivity . This stexposure , 38. In B. burgdorferi s.l., meaning that we did not examine study subjects for clinical disease. Despite high specificity in both the screening and confirmatory tests, we cannot fully exclude the very small chance that cross-reactions may have led to false-positive results among samples, for example, caused by present immune reactions to syphilis [Our study has limitations. First, we conducted a serosurvey for IgG and IgM antibodies for syphilis , relapsisyphilis  or herpesyphilis , 57). Fusyphilis , renderisyphilis . In our syphilis , 37, 48.B. burgdorferi s.l. in Bonn and additionally provides seropositivity estimates for IgM antibodies. Although we hypothesized an increase in seroprevalence due to reports of increased tick density and tick infection proportions in this region over the past few decades [In conclusion, this study provides an important update of IgG antibody seropositivity estimates for  decades , 27, we


The catalysts were systematically characterized by state‐of‐the‐art techniques. With increasing Sr content, the concentration of surface oxygen vacancy defects increases, which is beneficial for cyclohexene oxidation, but the surface concentration of less active Co2+ was also increased. However, Co2+ cations have a superior activity towards peroxide decomposition, which also plays an important role in cyclohexene oxidation. A Sr doping of 20 at. % was found to be the optimum in terms of activity and product selectivity. The catalyst also showed excellent reusability over three catalytic runs; this can be attributed to its highly stable particle size and morphology. Kinetic investigations revealed first‐order reaction kinetics for temperatures between 60 and 100 °C and an apparent activation energy of 68 kJ mol−1 for cyclohexene oxidation. Moreover, the reaction was not affected by the applied O2 pressure in the range from 10 to 20 bar. In situ attenuated total reflection infrared spectroscopy was used to monitor the conversion of cyclohexene and the formation of reaction products including the key intermediate cyclohex‐2‐ene‐1‐hydroperoxide; spin trap electron paramagnetic resonance spectroscopy provided strong evidence for a radical reaction pathway by identifying the cyclohexenyl alkoxyl radical.La A complex for a complex reaction: Lax1−SrxCoO3 nanoparticles were prepared by spray‐flame synthesis and applied in the liquid‐phase oxidation of cyclohexene with molecular O2. An optimum Sr doping of 20 at. % – with balanced amounts of oxygen vacancies and Co2+ cations – was found to be beneficial for cyclohexene conversion. In situ ATR‐IR and EPR spectroscopy verified the complex radical reaction network. The stable and low selectivity of 4 % to the epoxidation product cyclohexene oxide indicates a direct consecutive reaction to the diol. cyclohex‐2‐ene‐1‐ol selectivity decreases over time, indicating its consecutive oxidation to the corresponding ketone . Moreover, XRD patterns recorded after cyclohexene oxidation do not indicate any changes in phase purity or crystallinity .Comparing the catalytic properties of herein synthesized perovskites with a commercial analogue shows the superior catalytic activity and selectivity of the spray‐flame‐made nanoparticles with high surface areas . A commercial La3 nanoparticles results in increased cyclohexene conversion and ketone yield. This result can be attributed to the increasing concentration of oxygen vacancies with increasing Sr amount, as indicated by HAADF‐STEM . Unchanged XRD patterns  of the spent catalysts indicate the high stability of the Sr20 nanoparticles towards high pressure. These results confirm that cyclohexene oxidation is not limited by the applied O2 pressure revealing a zero‐order dependence on O2 pressure. A control experiment in the absence of O2 showed no cyclohexene conversion after 6 h of reaction, indicating that O2 is indispensable for cyclohexene oxidation and that surface or lattice oxygen from the perovskite oxide is not involved.Cyclohexene conversion and product selectivity as a function of applied OThe continuous increase in cyclohexene conversion as a function of temperature is presented in Figures R2>0.94), indicating again that cyclohexene oxidation over Sr20 follows first‐order reaction kinetics . The Arrhenius analysis results in a plot with high accuracy (R2=0.997) revealing an apparent activation energy of 67.8 kJ mol−1 , are molecules that form paramagnetic spin adducts upon reaction with reactive oxygen species and/or carbon‐centered radicals.aN and aH) of the unpaired electron spin and nuclei on the DMPO moiety. Cyclohexene oxidation over Sr40 was carried out to investigate the present radicals. Whereas control samples without DMPO added to the solution showed no EPR signal, samples prepared with DMPO exhibited the characteristic EPR of DMPO trapped radicals. Figure tert‐butyl‐nitroxide derivative..OC6H9) formed upon oxidation of .C6H9 during cyclohexene oxidation. This cyclohexenyl alkoxyl radical has been found in literature for manganese porphyrin‐catalyzed oxidation of diphenylmethane in presence of cyclohexene using PBN as a spin trap.tert‐butyl‐nitroxide derivative is probably due to decomposition of DMPO and is therefore not further considered. In summary, EPR spin trap experiments identified cyclohexene oxidation to proceed according to a radical pathway including the cyclohexenyl alkoxyl radical.EPR spin trap experiments were performed to identify possible radical pathways during cyclohexene oxidation. Spin traps, like the herein used 5,5‐dimethyl‐1‐pyrroline Cyclohexene oxidation follows a complex reaction network Scheme , enablinPrior to the in situ measurement, ATR‐IR spectra of reference samples in acetonitrile were recorded  to assign the characteristic bands to the reactant and the oxidation products, which are summarized in Table S3.2 atmosphere before pressurizing with molecular O2 and initiating the actual cyclohexene oxidation reaction (0 h). The recorded spectrum at 0 h is used for background subtraction. Similar to the spectral change over time in Figure −1 gradually decreases, representing the consumption of cyclohexene. Cyclohexene conversion and product selectivity were simultaneously determined by offline GC analysis . After 4 h, roughly 50 % of cyclohexene has been converted into its reaction products. All reaction products quantified by GC analysis can also be observed spectroscopically. The strong increase in the intensity of the C=O stretching vibration at 1690 cm−1 is due to the formation of cyclohex‐2‐ene‐1‐one, which is the main oxidation product (11.7 % yield) besides the hydroperoxide intermediate (10.2 %), the formation of which is represented by the vibration at 949 cm−1. Note that the characteristic vibration of the hydroperoxide is very weak so that peak intensities do not represent quantitative yields. In addition, the intensity of the stretching vibration at 1002 cm−1 is significantly increasing, demonstrating the formation of cyclohex‐2‐ene‐1‐ol with a yield of 3.4 % determined by offline GC analysis. Also, the formation of 7‐oxabicyclo[4.1.0]heptan‐2‐one (3.3 % yield) can be monitored by the increase in band intensity at 1713 cm−1 so that the formation of all reaction products assigned to the allylic pathway of the cyclohexene oxidation can be traced by in situ ATR‐IR spectroscopy. The selectivity to cyclohexene oxide as an epoxidation product is low, resulting in a yield of only 1.8 %, which is underlined by the low intensities of the assigned band for the alkoxy C−O stretching vibration at 1005 cm−1. The C−O stretching band at 1066 cm−1 assigned to cyclohexane‐1,2‐diol shows a significantly stronger increase in intensity. Also, GC analysis reveals a higher yield of cyclohexane‐1,2‐diol of 3.0 % as a consecutive product of cyclohexene oxide. Thus, it can be concluded that the hydrolysis of cyclohexene oxide to the diol occurs rapidly  formed upon oxidation of .C6H9. In situ ATR‐IR spectroscopy was employed to monitor reaction progress; this confirmed the complex reaction network with cyclohex‐2‐ene‐1‐hydroperoxide as key intermediate.For cyclohexene oxidation, Sr20 led to the highest conversion and selectivity, whereas higher or lower Sr amounts exhibited less pronounced catalytic activity. This can be attributed to the balanced amount of oxygen vacancies and CoThe authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.Supporting InformationClick here for additional data file.


Results: At program completion, and as indicated with an asterisk at the six month follow-up, participants had statistically significantly improved diet and exercise measures , improved mental health indicators  and improved social and cultural connection . Discussion: This is one of the first quantitative studies to demonstrate the profound effects that cultural learning and connection have on the health and well-being of Indigenous people and practices. It also demonstrates the specificity and effectiveness of a program created by and for tribal citizens. Future programs with Indigenous populations should work to center cultural connection and ensure that programs are created and directed by tribal community members.Introduction: Indigenous youth and young adults endure some of the highest rates of physical and mental health problems in the United States compared to their non-Indigenous counterparts. Colonization, oppression, and discrimination play a substantial role in these inequitable disease rates. However, culture  relates to the prevention of and recovery from illness in Indigenous populations. The Remember the Removal program aims to teach Indigenous youth and young adults tribally specific culture, history, and language to put them on a trajectory to become informed and culturally connected community leaders. We examined the program’s effects on health. Method: Thirty Remember the Removal program participants, mainly young adults, completed surveys four times: before the program’s start, at the end of the training period, at the program’s end, and at a six-month follow-up. Various indicators of physical, mental, spiritual, and cultural health and well-being were measured at each time period. Paired  Indigenous youth and adults face some of the worst health conditions in the United States including higher rates of depression, anxiety, post-traumatic stress disorder, obesity, diabetes, and cardiovascular disease compared to their non-Indigenous counterparts ,3,4,5,6.Health inequity arises from the multiple social and economic inequities that Indigenous people experience , includiTo counter the negative and pervasive effects of colonization and regain balance, tribes and communities have led efforts to revitalize their cultural and spiritual ways of life . These eOne program, the Remember the Removal program, began in 1984  by a graWe set out to assess the effect of the program on participants starting in 2015 given the legacy of community leaders that have been created through this program. While we are not administrators of the program, we collaborated with program staff to accomplish this goal of program assessment. Focus group results from the 1984 and the 2015 cohorts of the RTR program indicate that after this program, Cherokee youth feel more confident, knowledgeable, and connected to their Cherokee identity, have improved health behaviors, and are more involved in their tribal community . These rThe Cherokee Nation (CN) and Eastern Band of Cherokee Indians (EBCI) participate in the Remember the Removal (RTR) program yearly with slight differences between them. For instance, CN requires participants to be between the ages of 16–24 while there is no age requirement for EBCI participants; CN houses this program in the education department while the RTR program is within a diabetes prevention program at EBCI. Each tribe has unique selection criteria but generally, participants who share an interest in learning about Cherokee history and culture, as well as are committed to completing program requirements are ranked highest for program selection. A complete description of this program is detailed in a previous manuscript . For thiThe research project  was a collaborative effort between the researcher who is an enrolled citizen of the Cherokee Nation, and the RTR program staff at Cherokee Nation and at the Eastern Band of Cherokee Indians. Consistent with Indigenous and community-based participatory research methods ,37, thisThe purpose of this project was to assess the health effects of a Cherokee Nation-sponsored program, Remember the Removal. Inclusion criteria included that participants were selected by their respective tribes for the program. All participants completed an informed consent document and assent documents were completed by individuals and parents under the age of 18. The PI collaborated with program staff at each site to contact RTR participants to notify them about the research opportunity. Participants completed the survey online and a computer lab was available for those who did not have access to a computer. Participants received $30 and a small gift at each survey interval (×4). Gifts included Cherokee baskets, mugs, scarves, and a backpack with the RTR logo.t-test (n = 30). Therefore, there were 19 participants each year. The participant sample size at each time interval is presented in There are a limited number of RTR participants selected each year from each tribe given the safety concerns that present when there are too many bicyclists on the road at the same time. Therefore, we collected data for two years aiming to satisfy the minimum needs to complete a Health, illness, and well-being are concepts that are embedded in a cultural context . MeasureFor instance, within the physical domain, while some participants in the 1984 group no longer exercised at the same rate as they did at that time, during focus group discussions, many recounted skills around learning to exercise that are still utilized . Similarly, 2015 participants shared that they gained skills around shopping and consuming healthier foods during the program or reducing sugar-sweetened beverages so we ensured those measures were included .Concepts around mental health that were discussed in focus groups were related to experiences of historical trauma and myriad emotional responses to it  . FurtherBody Mass Index (BMI) and Diet: Participants’ height and weight, along with age were used to calculate BMI at each wave of the study.Food Intake: We assessed the intake of fruit, salty, sweet, and high-fat content foods, and sugary beverages by frequency based on nutritional guidelines,  .Physical Activity: The International Physical Activity Questionnaire-Short Form (IPAQ-SF) has 6 questions about different physical activities grouped into low , moderate, and vigorous. The frequency of activity is gathered by week and minutes per day if applicable. For example, “During the past 7 days, did you walk for at least ten minutes for any of these reasons?”Self-efficacy for Activity: The self-efficacy for activity scale was developed for youth to measure their perceived ability to successfully be physically active . ThirteePositive Mental Health: The mental health continuum—short form is a 14-item instrument used to assess positive mental health in terms of emotional (EWB), social (SWB), and psychological well-being (PWB) ,46. The Post-traumatic Stress Disorder. The Primary Care PTSD Screen (PC-PTSD-5) is a 5-item construct designed to measure PTSD symptoms and provide a preliminary diagnosis. A sample question from this tool is, “Have you been constantly on guard, watchful, or easily startled?” When administered by trained interviewers, this construct demonstrated perfect inter-rater reliability for diagnoses and κ > 0.95 at the item level .Stress: The global stress assessment is a one-item questionnaire used to assess participants’ overall stress using a 1-point scale, ranging from 1 (no stress) to 7 (extremely high stress).Depression: The Patient Health Questionnaire-9 (PHQ-9) is a nine-item measure of the diagnostic criteria for depression ,49,50. EAnxiety: The Generalized Anxiety Disorder 7-item Scale (GAD-7) is a seven-item questionnaire used to identify those with GAD and to determine the severity of their anxiety . The queAnger: Anger was measured using the tri-ethnic anger scale . QuestioMicroaggressions: The microaggressions measure has 11 items that examine experiences of bias and discrimination that relate to the participant’s cultural group membership. We deployed the adapted version by Sittner et al.  that wasHistorical Trauma. The Historical Loss and Associated Symptoms scales were developed and revised based on elders’ and tribal advisory boards’ comments and suggestions . The purSocial Support: The social support survey is a 19-item measure of functional support that comprises five subscales: emotional, informational, tangible, affectionate, and positive . The surCherokee Identity: The Multigroup Ethnic Identity Measure (MEIM) is a 20-item measure used to assess one’s subjective association with their ethnic group . The nonCherokee Language: One item was used to measure the frequency of use of the Cherokee language: “My ability to speak Cherokee now can be described as…” Responses were recorded on a five-point scale with zero representing ‘I cannot understand or speak’ and four representing ‘I am fluent’.Cherokee Traditional Ways: Participants were asked “How much do you live by or follow traditional Cherokee ways?” with a 5-level Likert scale ranging from 1  to 5 .Community Values: Cherokee Nation community values were measured using a 20-item instrument that was adapted for this project from a document created by Cherokee Nation regarding Cherokee-specific principles and directions around community relationships . The conDescriptive statistics were examined for all participant characteristics. All outcome data were examined for potential outliers. Distributions were found to be within normal symmetric boundaries and determined to be suitable for further analysis. The primary purpose of this program assessment was to analyze the change in participants from before they entered the program throughout each stage of the project to learn about patterns related to each stage of the program. Therefore, to evaluate change in participants’ physical, mental, and social/cultural health over time, paired t-tests were used to calculate mean differences in participants’ baseline scores compared to scores from each time interval . The general ‘rule of thumb’ for a paired t-test is 30 pairs, and despite a low sample size, we were able to meet this standard in all but one analysis that had 29 matched pairs (baseline-follow-up). All analyses were performed in SAS for Windows version 9.4 .Demographics: Two years of cohorts of RTR program participants were asked to participate in this research project. There were 38 participants overall (19 per year) with the majority being from the Cherokee Nation (63%). Women made up 58%; 36% reported having a college or advanced degree, and 89% reported living within their reservation or boundary see . The avep = 0.001; see Physical Health: Participants reported higher levels of physical activity (METs) from baseline through the training period (p = 0.01) and at intervention completion (p = 0.001); lower levels of salty/fatty foods from baseline to intervention (p = 0.02); and less sugary beverages were consumed from baseline to the completion of the training period (p = 0.03) and at completion of the intervention (p = 0.04). Participants reported improved eating habits during the program but not at the six month follow-up period: higher levels of fruit consumption were noted from baseline to the training period (p < 0.05), but higher levels of historical trauma (p = 0.02). At the completion of the intervention, participants reported lower levels of stress, anger, anxiety, PTSD, microaggression, and depression, and increased positive mental health and historical loss thoughts compared to baseline. At the six-month follow-up period, participants continued to report significantly improved positive mental health including less depression, reduced anger, and fewer reports of micro-aggressions . At the completion of the intervention, participants reported significantly higher levels of Cherokee identity (p < 0.01), traditional Cherokee ways (p = 0.001), social support (p < 0.005), and Cherokee community values (p < 0.01). At follow-up, only Cherokee identity remained significantly increased (p = 0.01) from baseline  and is comparable to other studies in which community-based participatory research principles, as well as Indigenous methods, are used . DespitePhysical health indicators , positive health behaviors , and self-efficacy for health behaviors approached or reached significance during or after the intervention but did not remain significant at the six-month post-test. However, diet improved during the program and including increased fruit consumption and reduced sugary beverage consumption. This is quite notable given the persistent and high rates of adolescent and adult obesity and Type II Diabetes in tribal communities . While tculture as prevention/treatment, which asserts that connection to or immersion in Indigenous culture has health-promoting impacts for Indigenous people and communities. In short, “culture is a social determinant of mental health/well-being for Indigenous/Native peoples” [Many mental health indicators improved during and after this program. This is particularly impressive given the lack of any Western mental health component to this intervention. This finding is congruent with the philosophy of peoples” . Connectpeoples” . These rpeoples” , suicidapeoples” , educatipeoples” , and carpeoples” ,66. For peoples” .In this study, participants reported increased historical loss thoughts. However, it is not surprising that thoughts of historical loss increase when there is an increase in teaching about historically traumatic events. Researchers have argued that…Implicit in the concept of historical trauma is that memories and consciousness of atrocities, such as the Trail of Tears, have multigenerational negative effects on group members, and becoming cognizant of atrocities even if this is a new awareness of the past can initiate one’s experiences of historical trauma”.“What is surprising and hopeful in this study is that historical loss was insignificant at the post-test. We hypothesize that this can be explained through the Indigenous-specific stress-disease process theory that calculates health outcomes in relation to Indigenous-specific stress and trauma, as well as protective social and cultural factors . For exaOur previous qualitative  and currThe National Indian Education Association promotes the use of Culturally and Linguistically Responsive Education as best practice for Indigenous students  and IndiLimitations: We recognize that this study has limitations, primarily the fact that the study population is small in nature, lacks a comparison group, and is specific and generalizable to only those who participated in the Remember the Removal program. The small participant size also limited the type of analysis we were able to use which we hope to improve in the future. Modeling, for example, would give us more information about the relationship between the variables.We employed a pre-post study design which limits our ability to draw meaningful conclusions from our study results given that participants self-selected and that we did not have a comparison group. However, this was one of the first studies to evaluate the health effects of a community-created cultural intervention in this population, therefore, it was an appropriate method to use. Future studies assessing cultural interventions should utilize culturally appropriate comparison methods to better isolate the effects of cultural intervention. For example, as described in Kaholokula et al.; “A waitlist control rather than a concurrent control group was a mandate of our community partners and stakeholders to ensure all participants were eventually offered the hula-based intervention.” .Additionally, we acknowledge that the CN and EBCI Remember the Removal programs include slight differences between them, particularly participant age eligibility, as well as some departmental differences. Such differences could play a role in determining whether the results from the two programs are truly comparable or should be combined. Furthermore, the project was carried out over two years of cohorts of the RTR program, and some participants were lost to follow-up between baseline and subsequent data collection periods.Strengths: Despite these limitations, quantitative health analysis of Indigenous community projects is novel and has demonstrated profound health effects without Western methods of health promotion. While countless Indigenous communities engage in their culture daily, this may be one of the first projects to evaluate a cultural program that was created completely within an Indigenous community absent of any academic or medical intervention . FurtherThis study adds to the body of research that supports culture as a critical component of positive health and well-being in Indigenous communities . TherefoWhile cultural connectivity is a key aspect of health and well-being for Indigenous people, the suppression of Indigenous knowledge and practices remains a problem in most sectors of our society and is an international violation of sovereignty ,82. Unti


The Kumamoto earthquake which occurred in April 2016 measured twice the maximum seismic intensity of 7, causing serious damage to the Kumamoto Prefecture. This study mainly focuses on the demand side of expenditures, estimating the monthly expenditures for 1 year before and after the earthquake. Then, using the multi-regional input–output table for Kumamoto Prefecture, we analyzes the ripple effects by region of the changes in monthly expenditures due to the earthquake. Expenditures in the prefecture in fiscal year 2016 by month decreased by a cumulative total of 592 billion yen because of the earthquake, which generated a value-added loss of 348 billion yen. On the other hand, expenditures increased by a cumulative total of 648 billion yen caused by reconstruction demand, inducing 375 billion yen in value-added gains. Thus, net increase of the value-added of 27 billion yen occupied 10.9% of net increase of the gross prefectural domestic product between fiscal years 2015–2016. The fluctuation of expenditures, induced production, and induced value-added caused by the earthquake is huge. Although the damage to the prefectural economy was severe, reconstruction demand exceeded it, resulting in a quick recovery. However, at the same time, there was a confirmed delay in restoration in industries that were almost unrelated to reconstruction and in regions with a heavy concentration of damage. The destructive earthquake that occurred in April 2016 with twice the maximum seismic intensity of 7 in the Kumamoto region caused enormous damage to the entire prefecture. In addition to human casualties and housing damage, the damaging of products and capital equipment in primary and secondary industries caused outrage and a stagnation of production activities. The subsequent destruction of the supply chain spread the negative impact across the country.The stagnation of production activities decreased corporate surplus and workers’ income and resulted in the reduction of consumer demand and capital formation. Furthermore, anxiety for the future and the reputational damage of the local people due to the earthquakes caused a decline in consumerism and tourism. On the other hand, the active support by the central and local government for the restoration of the infrastructure and the reconstruction of business and personal activities for the local people had an impact on raising consumer demand and capital formation. Thus, the serious damages from the earthquake may have been compensated for by the public expenditure and the people’s efforts to overcome the difficulties they faced. The physical and economic impacts of the earthquake may differ by region.The purpose of this study is to use the multi-regional input–output (MRIO) table to investigate the economic impacts of the earthquake in the regions of the Kumamoto Prefecture and the degree of recovery made by the restoration and reconstruction program. While an input–output analysis on the supply constraint model reflects an estimation of loss due to disasters, such as the Kumamoto earthquake, this study focuses on the demand side, which involves the change of expenditures in the prefecture by “damage” and “reconstruction.” We elucidate these effects on each region in the prefecture. Two databases, “Regional Domestic Expenditure Index” (RDEI) and “Prefectural Accounts,” enable this study to estimate the expenses of “damage” and “reconstruction” by month and the measure change of spending that annually based data does not grasp. We also estimate their positive and negative economic ripple effects using the MRIO table, which consists of three regions in the Kumamoto Prefecture  as well as other parts of Japan. Figure 1The structure of this paper is as follows: the next section explains the damage and reconstruction of the earthquake for background and reviews previous literature. The third section describes the methodology for the estimation and analysis of changes in expenditures and those ripple effects. The fourth section discusses the estimation result. The last section is the conclusion.On April 14th, 2016, a magnitude 6.5 earthquake that measured a seismic intensity of 7 struck the Kumamoto region. Furthermore, 2 days after, a magnitude 7.3 earthquake that measured an intensity of 7 struck the region again. 4484 aftershocks over an intensity of 1 were recorded through March 2018.3In addition, production facilities, equipment, and stores related to agriculture, forestry, fisheries, commerce and industry, and social infrastructure such as water, sewage, electricity, gas facilities and roads, as well as cultural assets were also severely damaged. The prefectural office and the Cabinet office estimated the capital stock damage at 3.8 trillion yen, which accounted for 11% of the prefecture’s total capital stock of 34 trillion yen. The Cabinet office evaluated approximately 81–113 billion yen as the amount of flow damage during the month after the earthquake.5Whereas torrential rain, typhoons, and COVID-19 struck the region after the earthquake, reconstruction is progressing steadily. The maximum number of evacuees recorded was 184,000 just after the earthquake. 90% of evacuees were able to leave the shelters 1 month later, and all shelters were eliminated by November 2016.7First, the damage in the regions targeted for analysis is reviewed. The earthquake, with its epicenter in Kamimashiki County in the northern area of the prefecture just southeast of Kumamoto City in Fig. Second, review the changes on the demand side after the earthquake based on some economic statistics. Figure Regarding private residential investment, while the level was slightly below the FY2015 average in May 2016, it has been over the average since then, with rapid growth since November 2016. According to the Building Starts Statistics (BSS), the construction floor area is beginning to expand since October 2016. In addition, the number of housings starts above the FY2015 level has cumulatively totaled 9587 through 2018, more than the number of housing units completely destroyed by the earthquake.9In May 2016, private non-residential investment recovered and exceeded the previous fiscal year’s average from June through September 2017. After being below the average in November, its level immediately recovered and has been high ever since. After the fluctuation between April and July 2016, public investment gradually increased, and since December 2016, it has remained well above the average of the previous fiscal year.Emergency restoration demand rose immediately after the earthquake. Thereafter, although the reaction to the emergency spending and the shortage of construction-related manpower and equipment made demand decrease or slow down, full-fledged demand for reconstruction rose as production activities were revitalized by facility restoration projects, subsidies, and special loans.Looking at the number of tourists in Fig. Appendix Table There are two approaches to discuss the economic impacts of the earthquake: supply side and demand side.The former approach focuses on the impacts of the disruption of the supply chain to evaluate production loss caused by the earthquake. Hasebe  proposesOn the other hand, the latter approach focuses on amount of damage, economic ripple effects by restoration activities, and the process of reconstruction. Ashiya and Jinushi  estimateIn recent years, the trend in input–output analysis of disasters has tended to emphasize the evaluation of production losses . In the case of the Kumamoto earthquake, demand-side analysis is limited to tourism and some manufacturing industries, while analysis of household consumption, investment, and government spending is insufficient. The supply constraint model measures the impact of supply chain disruptions and tends to focus on effects outside the affected areas, with little reference to spillover effects within Kumamoto Prefecture.Based on the previous studies, this study focuses on demand side and analyze impacts of change in expenditure by region and month due to damage and reconstruction demand caused the Kumamoto earthquake using multi-regional input-out table for Kumamoto Prefecture, which we estimate independently. This study follows these demand side approach and estimates backward linkage effects by multi-regional Leontief model.This study uses the MRIO table for Kumamoto Prefecture in 2015, which consists of 105 industrial sectors and 4 regions: Kumamoto Prefecture , and the other parts of Japan. Using a non-survey method, the intra-regional input–output tables each region are compiled based on the input–output (IO) tables for the prefecture and Japan, and other statistics. Inter-regional transactions were estimated by referring Maekawa 's method12Monthly base expenditure is used to examine the impacts of damages from the earthquake and the reconstruction process. The Prefectural Accounts only publishes the yearly base final demand. We need to estimate monthly base final demand by industry and region. Katayama and Yagi  allocateFollowing their method, we calculate expenditures for each month by allocating nominal GPDP as in the Appendix Table Eligible expenditure items of final demand are (1) consumption of households, private Investment, (2) residential, (3) non-residential], (4) public Investment, and (5) tourism consumption. The target regions are Kumamoto City, Northern and Southern prefectures, and number of industries spans 105 sectors. The target period is 1 year before and after the earthquake (from April 2015 to May 2017).151) Consumption of householdsMultiplying the itemized expenditure according to purpose from the GPDP using the indexed spending by item of the FIES2) Private residential investmentThe monthly expenses are allocated to each region based on regional ratios of the construction floor area obtained from the BSS. Then, the gross regional domestic fixed capital formation (GRDFCF) (private sector) in 2016 and 2017 is calculated by multiplying the gross regional domestic fixed capital formation of the MRIO table by the growth rate of same item of the updated IO table for Japan in 2016 and 2017. These data are divided into residential and non-residential in accordance with the ratio obtained from the BSS and the Building Remodeling and Renewal Survey. Finally, the expenditure by industry is estimated by multiplying the composition ratio of residential parts by the spending by month and region.3) Private non-residential investmentThe private non-residential investment by month is distributed to each region using regional ratios taken from the acquisition amount of property, plant, and equipment in the Census of Manufacture.4) Public investmentThe public investment by month is allocated to each region in accordance with regional ratios that obtained the investment expenses in the Settlement Cards. In addition, the GRDFCF (public sector) of the MRIO table is updated to 2016 and 2017 in a similar way as 2). Afterward, the expenditure by industry is valued by multiplying the composition ratio of them and the spending by month and region.5) Tourism consumptionThe monthly tourism consumption by region (MTCR) is estimated by multiplying the number of tourists  by per capita consumption taken from the Kumamoto Tourism Statistics.There are various interpretation of reconstruction and its effects. For example, return of certain economic indicators restore to before earthquake levels, or government spending to cope with the disaster. This study analyzes change in expenditure before and after the earthquake regardless of public or private, considering surplus above levels before the earthquake to reconstruction demand. The difference between the same months in FY2015 and FY2016 by item, region, and industry is obtained from the monthly expenditures estimated by the above procedure. If the amount of the expense in each month of FY 2016 is less than the previous fiscal year, the impact is treated as “decrease” due to earthquake damage. If the amount in FY2016 exceeds that of the previous fiscal year, the impact is treated as “increase” due to reconstruction demand.To estimate economic ripple effects of the change in the final demand, the open Kumamoto MRIO table in 2015Supply–demand balance on the MRIO table with endogenous import isSolving  for \docIf reginal final demand changes by Multiply the value-added ratio by Assume a case where consumption is declining due to future uncertainty caused by the damage from the earthquake and the resulting stagnation of production activities. In this case, The monthly change vector of final demand by item, which is difference between same month FY2015-2016, is denoted bySuperscript The superscript  in Eqs.  and 4)  \documenThe superscript rom Eqs.  and 8)  \documenThe annual cumulative increase and decrease in expenditure and its ripple effects, which are estimated by methods of above section, by region in 1 year are shown in Table According to Table Expenditure in the prefecture dropped down in from May to August 2016, then as the figure indicates, gradually recovered. From November 2016, it rose. Regarding household consumption, after a decrease for 6 months beginning in May, it recovered. The change in private residential investment was always positive except in June 2016 compared to FY2015. Private non-residential investment fell throughout 2016 except in September, with recovery in January and February of 2017. Public investment was positive throughout the fiscal year. In contrast, tourism consumption remained negative throughout FY2016.Appendix Table The impacts on each region are as follows. In Kumamoto City, where earthquake damage was moderate, annual cumulative drop and rise was recorded at 185 billion yen and 230 billion yen, respectively. The monthly expenditure exceeded the previous year's level immediately after the earthquake due to a temporary increase in household consumption, but then plunged and stagnated for several months. It almost recovered in November 2016 and subsequently experienced a significant increase due to the growth of private residential investment and public investment. It is thought that the increase in household consumption immediately after the disaster was an emergency response to the numerous injuries and damage to housing, with a sharp drop due to the backlash and uncertainty about the future, followed by an increase in full-fledged reconstruction demand.In the northern part of the prefecture, where main infrastructures were severely damaged, the annual cumulative decrease and increase were 297 billion yen and 246 billion yen, respectively. Both amounts were the largest among the three regions. Although public investment was expanded to overcome the damage, total spending did not recover in 2016 because of difficulty in restoring private non-residential investment and household and tourism consumption. Consequently, noticeable decreases appeared in accommodations and food service activities, and general machinery. The notable weakness in non-residential investment and tourism consumption indicates the extent of the damage to people and buildings and its harmful rumors. In line with the scale of the damage, public investment also expanded, with the largest net increase, but it did not cover even half of the decline in other expenditures.In the southern part of the prefecture, where the amount of damage suffered was small, the recorded annual cumulative decline was 110 billion yen and the annual cumulative increase was 171 billion yen. Both amounts were the smallest among the regions, but the net change of expenditure was the biggest. Although this area experienced slightly decreased expenditures in July and August 2016 due to a decline in household consumption, increased spending on non-residential and public investment pushed the other months spending above the previous fiscal year’s level. However, the annual cumulative total of residential investment was the only net decrease in the prefecture, due in part to the extremely low number of housing collapses. Looking at industry, as a result of the increased spending, the region conspicuously gained in the activities of construction and professional service.It is estimated that the annual cumulative decrease in prefecture spending pushed down final demand by 425 billion yen and production by 553 billion yen in the prefecture as a whole. On the other hand, the annual cumulative increase in expenditure boosted final demand by 487 billion yen and induced 648 billion yen gain in production in the prefecture as a whole. As a result, prefectural production is estimated to have grown by 94 billion yen in 2016. This amount accounts for 19.9% of the increase in output of the prefectural accounts in FY2015-2016.In addition, annual cumulative value-added loss was 348 billion yen, and annual cumulative gain was 375 billion yen; that resulted in a net gain of 27 billion yen. This net gain was equivalent to 10.9% of the increase in GPDP of 246 billion yen over the same period. The change of final demand are calculated based on GPDP (expenditure). Therefore, the Induced value-added caused by those fitAccording to Table 25While expenditure in the northern prefecture experienced the most decrease among the regions, drop in imports due to the decline in the non-residential investment demand. Consequently, net change in production became positive in this area. Comparing Figs. By region and industry (Appendix Table This study investigated the increase and decrease in expenditure due to the damage and reconstruction demand caused by the Kumamoto earthquake, and analyzed the impact of the earthquake on production and added value in and outside of the prefecture using the MRIO table.Our findings indicate that earthquake damage caused an annual cumulative decrease in expenditures of 592 billion yen and value-added losses of 348 billion yen in the prefecture as a whole. Reconstruction demand led to an annual cumulative increase in spending of 648 billion yen and a value-added gain of 375 billion yen in the prefecture. The net increase in value-added of 27 billion yen, which difference of increase and decrease in value-added inducement, accounted for 10.9% of the total GPDP gain during the same period. Looking at monthly transitional changes, the expenditure level was less than the previous fiscal year’s level during several months due to the reduction of household consumption, tourism consumption, and private non-residential investment. A few months after the earthquake, the level recovered more than that of the previous fiscal year because of the rapid expansion of private residential and public investment. In the northern prefecture, where damage was particularly bad, spending fell sharply due to a drop in consumption and non-residential investment, while an expansion of production through residential and public investment compensated for these losses to some extent. In Kumamoto City, where the damage was moderate, though an increase in expenditures was significantly higher than the decrease, net gain in value-added was significantly small due to leakage of these demand to outside the city. In the southern prefecture, where damage was relatively mild, both expenditure and value-added loss exceeded the previous fiscal year’s levels for many months due to the expansion of non-residential investment, and the excess of the increase was the largest among the three regions. Outside the prefecture experienced increase and decrease in demand about the same as that of southern prefecture through trade, and the net rise in value-added greater than that of the prefecture.In this way, the monthly increase and decrease in expenditures and its induced production and value-added owing to the Kumamoto earthquake was very large, and the damage to the prefecture’s economy was enormous. Recovery was achieved in a short period of time by virtue of reconstruction-related demand that exceeded the economic damage. However, this is only true for the prefecture's economy as a whole, a delay in restoration was observed in areas, where damage was concentrated and in industries with weak links to reconstruction-related demand. Our results also show that the change in expenditure within the prefecture had significant impact on the other parts of Japan. To our best knowledge this is the first time to use the monthly data by region, item, and industry for the investigation of the economic impacts of the Kumamoto earthquake.However, there are several issues to be considered. As a final demand, government consumption and imports/exports which are not included in the scope of this study, have a considerable weight in the gross prefectural domestic product. Thus, the impact of changes in these items is expected to be larger than our estimation. In addition, a comparison of the estimation results with the prefectural and municipal accounts suggests a bias in the allocation of expenditure to industries and regions.


A full understanding of the pathways from efficacious interventions to population impact requires rigorous effectiveness evaluations conducted under realistic scale-up conditions at country level. In this paper, we introduce a deductive framework that underpins effectiveness evaluations. This framework forms the theoretical and conceptual basis for the ‘Real Accountability: Data Analysis for Results’ (RADAR) project, intended to address gaps in guidance and tools for the evaluation of projects being implemented at scale to reduce mortality among women and children. These gaps include needs for a framework to guide decisions about evaluations and practical measurement tools, as well as increased capacity in evaluation practice among donors and program planners at global, national and project levels. RADAR aimed to improve the evidence base for program and policy decisions in reproductive, maternal, newborn and child health and nutrition (RMNCH&N). We focus on five linked methodological steps – presented as core evaluation questions – for designing and implementing effectiveness evaluation of large-scale programs that support both the needs of program managers to improve their programs and the needs of donors to meet their accountability responsibilities. RADAR has operationalized each step with a tool to facilitate its application. We also describe cross-cutting methodological issues and broader contextual factors that affect the planning and implementation of such evaluations. We conclude with proposals for how the global RMNCH&N community can support rigorous program evaluations and make better use of the resulting evidence. Evaluations of the effectiveness of programs being implemented at scale under real-world, non-trial conditions are essential to continue and expand recent gains in the health and nutrition of women and children, especially those living in low-resource or conflict settings. Such evaluations go beyond global public health metrics and produce information relevant to program improvement at the local and national levels . ExampleFew large-scale effectiveness evaluations are conducted . Too oftFurthermore, large-scale RMNCH&N evaluations frequently fall short of the minimum technical standards needed to produce accurate and actionable conclusions, either at the level of the individual program or when data from multiple programs are concatenated to support higher-level estimates of impact . A recenGiven the challenges and cost of conducting full RMNCH&N effectiveness evaluations, there is also an important and too-often-missed opportunity for learning from the many less ambitious assessment activities conducted or commissioned by individual donors, projects and programs. At present, there is no registry for RMNCH&N evaluations, and no systematic effort to compile results and use them to inform policies and programs. Work over the last decade by the multi-partner ‘Countdown to 2030 for Women’s, Children’s, and Adolescents’ Health’  and otheIn this paper, we aim to encourage further commitment to and investment in high-quality effectiveness evaluations of RMNCH&N programs by providing a clear conceptual approach and summarizing the availability of new tools and methods to support its application. Many of these resources have been developed, tested and refined as part of the ‘Real Accountability: Data Analysis for Results’ (RADAR) project , a five-Program managers, governments and donors have overlapping information needs relative to RMNCH&N programs. In 2010, MNCH&N partner organizations agreed on a common framework to guide program evaluation  [10]. InRADAR provides specific guidance and tools to help program managers in LMICs and their donors respond to the five core evaluation questions efficiently, with reporting broken out by key equity variables . RADAR focused first on helping country programs collect, analyze and use data relative to these questions so that they could improve their programs while promoting the use of indicators and methodologies amenable to rolling-up results to meet Canada’s commitments relative to the broader RMNCH&N accountability agenda .LiST) is purposively designed to support this type of analysis and the design of programs that will save women’s and children’s lives. LiST provides users with up-to-date estimates of the effectiveness of RMNCH&N interventions on specific causes of and risk factors for maternal and child deaths, as well as epidemiological profiles and estimates of intervention coverage at national and – where available – subnational levels in LMICs [RMNCH&N programs must use their limited resources to deliver interventions that match the specific health and nutrition needs of women and children in their context. Although this may seem obvious, it is often not the case. Examples include programs in low child-mortality settings that focus on improved breastfeeding as a way to reduce deaths among under children under five , or progin LMICs .Evaluation Planning Tool allows users to create, edit and share impact models [LiST Visualizers allow users to explore examples of previously developed impact models, overlaid with relevant annotations [RMNCH&N programs being delivered at scale in low-resource countries often fail to produce measurable impact. One reason for this failure is that neither the program nor the evaluation team have committed to a fully specified program impact pathway, describing the range of activities and steps that must be completed successfully for the potential impact of the focus interventions to realize their expected effects on health and nutrition. We cited two examples of incomplete impact models resulting in impact failure above ,3. The Rt models , and theotations . Fully sSeveral large-scale effectiveness evaluations conducted over the past decade have demonstrated the importance of assessing each of the separate elements of the program impact model – implementation strength, service quality and service utilization – and combining the results to produce an estimate of expected impact ,3,19–21.Coverage, defined as the proportion of the population in need of a health intervention who receives it, is an essential requirement for impact and must be included in the plan for any evaluation of RMNCH&N program impact. By definition, coverage must be measured at the population level, and therefore requires population-based data most often obtained from household surveys. Recent advances in the methodological issues surrounding coverage measurement have led to a better understanding of the limitations of available measurement methods, and the refinement of globally recommended standard indicators for RMNCH&N intervention coverage . Existinhttps://www.radar-project.org/coverage-survey).Piloting of the RADAR coverage tool by partners highlighted the many technical and logistical challenges confronting program implementers who decide to conduct a survey. The tool therefore includes a set of resources to facilitate survey planning, implementation, and analysis  or both performance and impact (2%) .LiST tool was originally designed to meet this need [LiST tool with greatly expanded accessibility and user support [For programs within which the previous four core evaluation questions have been answered affirmatively, impact can be expected – if sufficient time has elapsed to allow the program to result in measurable changes at the population level. But can this impact be measured reasonably well and at reasonable cost by individual programs and their partners? Many of the health events that are of greatest importance for women and children – deaths, early births, and changes in nutritional status – are relatively rare events, requiring enormous sample sizes and resource-intensive measurement strategies that extend over long periods and are not feasible for use in most program evaluations. In settings where MICS, DHS, or other ambitious measurement efforts have been carried out, program evaluators can often access the data to conduct follow-up analyses that produce measured impact results relevant to their specific program. In most evaluations, however, this is not possible, and the expected impact can only be confirmed through modeling. The his need , and has support .Although LiST OnLine may not be the sole solution, a clear focus on health and nutrition impact is essential for all RMNCH&N evaluations. Even if time or resources preclude impact measurement, alternatives now exist. LiST and other modeling tools, and firm adherence to the use of an impact model that can support plausible inferences about program impact using available data , can proDespite their public health importance, rigorous evaluations of RMNCH&N programs being implemented at scale in low-resource settings are rare, and little attention has been directed at defining and addressing the special methodological challenges they present over and above evaluations conducted under more controlled conditions. Design challenges in conducting large-scale RMNCH&N evaluations reflect those in the broader sphere of causal inference in public health [e.g. well, and interpreting their findings in the context of a clearly specified impact model. Investing in less-than-rigorous measurement activities does not contribute and should be avoided.lth e.g. , includilth e.g. . If timeTiming is a critical challenge in large-scale evaluations for many reasons. For example, evaluators do not always control the launch or speed of intervention roll-out. Regardless of evaluator control over implementation calendars, unforeseen changes in program implementation may require quick changes in evaluation design, and interventions within a program can vary widely in the time required to result in measurable impact . Evaluating a program before the component interventions have a reasonable probability of achieving population impact is one of the most common mistakes in the effectiveness evaluations [luations .Sample size is often a limiting factor in determining which of the core evaluation questions can be addressed, with what level of confidence, and whether changes in health outcomes or impact can be attributed to a specific intervention or strategy. Decisions about design – whether the feasibility of geographic or historical comparison areas, acceptable levels of precision and power, or measuring the impact of individual interventions vs. packages of interventions vs. delivery strategies for multiple interventions – all depend on the feasibility and affordability of obtaining adequate sample sizes for analysis. Sample size considerations often include the need to capture measurable changes in several interventions simultaneously, some of which may reflect relatively rare events or smaller target populations . Too often overlooked is the fact that stratification to support equity analyses or examine the effects of contextual factors requires enlarged sample sizes because each categorical subgroup requires adequate numbers to support meaningful conclusions.Documentation of program implementation, as well as contextual factors affecting intervention roll-out and potential effectiveness  is needed to support attribution of positive outcomes to a program, and to rule out alternative explanations , as well as to assess the extent to which the evaluation results might be generalizable to other settings  [alidity) . Documenalidity) . EvaluatAn additional crucial technical issue is recognizing that even the best-designed evaluations, based on rigorous data related to the five core evaluation questions, is unlikely to provide a full explanation of why a specific strategy, program or intervention results in a particular level of population health impact. Additional complementary studies, using qualitative methods and political-historical-structural analysis, can enhance the understanding of ‘what works’ in RMNCH&N programs and provide important guidance for those seeking to improve program impact .Despite these design challenges and costs, investments in rigorous evaluations of RMNCH&N programs being implemented in real-world contexts are essential, and provide good value in terms of informing future programs that will save maternal and child lives.Large-scale evaluations are affected not only by technical concerns such as those described above but also by characteristics of the broader context that affect which of the many potential evaluation questions are given priority, whether evaluations are adequately funded and by whom, and the ways in which large-scale evaluations are currently tracked. We highlight a selection of these contextual factors in this section.Funding: One fundamental determinant of whether and how large-scale evaluations are conducted is the availability of sufficient funding. Rigorous, large-scale effectiveness evaluations of RMNCH&N programs in situ require multiple data collection activities over several years. They are expensive, challenging to design and implement, and require resource-intensive quality control. The resulting data sets can be fully utilized to generate learning only through advanced analytical techniques, and often produce mixed results – pointing to some successes, but in most cases also highlighting deficiencies in program design or implementation. For agencies or organizations that need fast and positive results to maintain their political or financial support, there are disincentives associated with this type of evaluation. They are risky, because they may produce results pointing to weaknesses in the program and its impact, jeopardizing continued funding [ funding . These e funding .The mirage of global public health metrics: Inadequate funding for large-scale effectiveness evaluations is exacerbated by the incentive structures guiding such investments. BMJ Global Health has fostered a recent and welcome discussion of the tensions between the needs of aid agencies and governments to demonstrate success and the scientific standards that should guide the design and conduct of objective global health evaluations [luations ,40. Poteluations . The valLack of a systematic tracking mechanism: Current practices surrounding large-scale RMNCH&N evaluations are not organized in ways that promote the use of results to improve programs. There is no systematic registry for planned RMNCH&N evaluations, no systematic archive for results generated from these evaluations, and no systematic mechanism for synthesizing these results and making them available to those who can use them to improve policies and programs. Largely as a result, few current evaluations address the sustainability of programs [programs  – somethRegistration of evaluation protocols. A systematic tracking mechanism or registry for RMNCH&N evaluations, similar to that for clinical trials [l trials , is needResults repository for program evaluations. The results of most program evaluations, and particularly internal evaluations conducted by implementing organizations, do not result in published, peer-reviewed publications, and are therefore not available to those who most need to learn from them. A repository, or archive, based on quality standards and perhaps even anonymized data sets, is needed as a foundation for learning.Periodic, subject-specific knowledge syntheses gained from the evaluations. Ensuring data sets from large-scale evaluations are publically available would lay a foundation for syntheses of what is being learned. Cochrane provides this essential service for randomized controlled trials [d trials . The Camd trials , includiWe need a new, systematic approach to tracking large-scale effectiveness evaluations, driven by the need to strengthen the evidence base on how to deliver and sustain effective programs for women and children. Rather than relying on individual donors and their immediate priorities, RMNCH&N program effectiveness evaluations should be recognized as a global common good – adequately funded and based on an evolving, theory-driven framework that supports meta-analyses – with results communicated proactively to those making decisions about RMNCH&N policies, programs and investment strategies. This new approach should include three distinct and complementary components:Trusted evidence. Informed decisions. Better health.’ would be an excellent starting point, as would the principles established by the Campbell Collaboration in 2017 [A set of targeted, multi-country, prospective, large-scale effectiveness evaluations could serve as the backbone of this initiative, with systematic incorporation of findings from more-targeted evaluations. The initiative would need to be led by an organization with deep, wide and multidisciplinary technical expertise, capable of maintaining independence from those who fund, implement and advocate for specific interventions, delivery strategies or programs. It would differ from past initiatives on behalf of women and children that combined political and technical roles, such as the Partnership for Maternal, Newborn and Child Health  or the m in 2017 .Rigorous impact evaluations of programs intended to improve the health and nutrition of women and children under real-world, non-trial conditions, produce essential information that is not available from other sources that is needed to inform program and policy decisions. The learning generated by these evaluations should be viewed as a ‘global common good’ to promote the health and nutrition of women and children. Ensuring accountability among aid agencies is also important, and we can do a better job of assisting these agencies in planning more focused, time-limited evaluation activities that are part of a common evaluation framework for RMNCH&N. RADAR has contributed by providing practical guidelines and tools to support these evaluations. Good evaluation data can serve as an important counterbalance to the growing dominance of global public health metrics with limited local and national relevance.We need re-invigorated efforts to ensure agreement on a common evaluation framework for RMNCH&N, including evidence-based impact models and standard indicators that can be measured accurately using rigorous methods. Modeling tools that use the best available evidence on intervention effectiveness and local epidemiology, and can translate program gains in coverage and quality into estimates of impact need continued support. We also need a mechanism to ensure that the results from all RMNCH&N evaluations – both large and small – are registered and assessed for quality, made publicly available, and synthesized regularly to increase the knowledge base on how best to improve the health and nutrition of women and children.


While the combined approach was associated with a significantly higher DY for lung cancer diagnosis  and sarcoidosis , no significant differences in DY were calculated for subgroups with smaller sample sizes such as lymphoma. No major adverse events were observed. Using a 1.5 mm mini-forceps is a safe and feasible technique for biopsy of mediastinal or hilar LAD or masses with superior overall DY compared to EBUS-TBNA as a standalone technique.When evaluating mediastinal/hilar lymphadenopathy (LAD) or masses, guidelines recommend endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) as an initial technique for tissue analysis and diagnosis. However, owing to the small sample size obtained by needle aspiration, its diagnostic yield (DY) is limited. EBUS transbronchial forceps biopsy (TBFB) used as a complimentary technique to EBUS-TBNA might allow for better histopathological evaluation, thus improving DY. In this retrospective bicentric study, we assessed the DY and safety of an EBUS-guided 1.5 mm mini-forceps biopsy combined with EBUS-TBNA for the diagnosis of mediastinal/hilar LAD or masses compared to EBUS-TBNA alone. In total, 105 patients were enrolled. The overall DY was 61.9% and 85.7% for TBNA alone and EBUS-TBNA combined with EBUS-TBFB, respectively ( Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is established as a safe and minimally invasive technique for cytological examination of mediastinal and hilar lymphadenopathy (LAD) with a high diagnostic yield (DY) ,2,3. AccTo overcome the abovementioned limitations, the use of an EBUS-guided transbronchial forceps biopsy (TBFB) has been proposed and evaluated in several studies yielding improved diagnostic accuracy ,16,17,18For the present retrospective study, we enrolled all patients with mediastinal/hilar LAD or masses detected by chest computed tomography (CT) who underwent EBUS-TBNA and subsequent EBUS-TBFB performed by three experienced interventional pulmonologists  at the University Hospital Zurich or at the Clinic St. Anna, Lucerne from 1 January 2020 to 31 December 2020 when sarcoidosis, lymphoma, or infection including tuberculosis was suspected, or when sufficient tissue was required for cancer staging or diagnosis. Patients were included if they were 18 years or older and written informed consent was obtained.The primary outcome was the overall DY of EBUS-TBFB in addition to EBUS-TBNA compared to EBUS-TBNA alone. The secondary outcome was safety  and technical feasibility. The study was approved by the Competent Ethics Committee of the Cantons of Zurich (BASEC-ID 2019-02479) and Lucerne (BASEC-ID 2020-00136-L).All bronchoscopies were performed under either moderate sedation or general anesthesia according to the examiner’s decision in in- or outpatient setting. Following airway inspection using a flexible Olympus bronchoscope (190 series), the lymph node stations 2, 4, 7, 10, and 11 from both sides, in addition to a possible mediastinal/hilar mass, were systematically assessed using an Olympus EBUS bronchoscope . Lymph nodes with a diameter equal or greater than 10 mm were sampled with three passes with a minimum of 10 advances per site using a 19-gauge needle  or a 22-gauge needle  according to the discretion of the bronchoscopist.After identification of the target lymph node or mass by EBUS for subsequent TBFB according to size and appearance of malignancy, another pass with the EBUS needle was added. In order to augment the puncture hole, the needle sheath was advanced through the bronchial wall into the lymph node/lesion and moved forward and backward several times. After extraction of the EBUS needle and sheath, respectively, a closed mini-forceps  was advanced through the working channel of the EBUS bronchoscope to re-enter the lymph node or mass through the pre-existing puncture hole while avoiding any movement of the bronchoscope. After penetration of the capsule of the lymph node, the forceps was opened and advanced until reaching the distal end of the lymph node. At the distal end, the forceps was closed and pulled for each specimen. This procedure was repeated four to five times under real-time imaging using EBUS. Finally, the closed mini-forceps was withdrawn through the working channel.Cytological specimens obtained using EBUS-TBNA were processed per institutional protocol and examined on a per node basis. The specimens were preserved in normal saline and immediately transferred to the respective Institutes of Pathology.EBUS-TBFB specimens were processed as histology specimens and placed into formalin solution for permanent fixation. All specimens were analyzed by pathologists at the pathology departments of the University Hospital Zurich and at the Lucerne Cantonal Hospital, respectively.All patients were routinely screened for pneumothorax with immediate lung ultrasound (LUS) and a chest radiograph (CXR) within 2 h post procedure. In addition, patients were asked to measure their body temperature daily during 7 days after the intervention and report temperatures above 38.5 °C lasting for more than 24 h to screen for a possible pneumonia or mediastinitis.The primary endpoint was the DY of EBUS-TBNA and EBUS-TBNA combined with EBUS-TBFB overall and among the subgroups. Secondary endpoints were its technical feasibility and safety. The DY was defined as the percentage of patients for whom at least one of the respective samples  was diagnostic. At least one of the samples of TBNA or TBFB had to be diagnostic to define the procedure as diagnostic. The detection of atypical or highly suspicious cells was not deemed diagnostic and, therefore, considered as negative cases. If EBUS-TBNA or EBUS-TBFB samples correctly excluded an alternative diagnosis, e.g., the exclusion of sarcoidosis, the procedure was also considered diagnostic.If EBUS-TBNA or EBUS-TBFB specimens were not diagnostic or suitable for analysis, the final diagnosis was made either by surgical biopsy (mediastinoscopy or through sampling at another site), by re-bronchoscopy or by follow-up.p-value < 0.05.Descriptive statistics were used to illustrate demographics and patient characteristics. Groups were compared with McNemar’s test using the SPSS version 26.0.0.0. . Statistical significance was defined as a In 1 year, 179 patients were enrolled in the study. A total of 36 patients were excluded because EBUS-TBFB was technically not possible, mostly due to the inability to penetrate the bronchial wall. Among these 36 patients, the 19-gauge needle was used in 28 patients (77.8%). Both TBNA and TBFB were successfully conducted in the remaining 143 patients, of which 105 ) were totally included . Most prn = 2, thymus carcinoma n = 1, melanoma n = 1, breast cancer n = 1, sarcoma n = 1, and ovarian carcinosarcoma n = 1), and other diagnosis in 18 (17.1%) patients. Other diagnoses included infectious diseases, inflammatory diseases, pneumoconiosis, and interstitial lung diseases.Indications for EBUS-TBNA and EBUS-TBFB, separated by the final diagnoses, are presented in p < 0.001). Thus, the combination of EBUS-TBFB and EBUS-TBNA provided additional or superior diagnostic information in 25 patients (23.8%) as compared to EBUS-TBNA alone . Conversely, in 10 patients (9.5%), the diagnosis was exclusively established by TBNA . Overall, no significant difference in DY between 19-gauge TBNA biopsies and 22-gauge TBNA biopsies was calculated .Overall, EBUS-TBNA as a standalone procedure yielded the final diagnosis in 61.9% of the patients compared to 85.7% when combining EBUS-TBNA and EBUS-TBFB, resulting in a significant difference in DY between the two techniques  cases. A total of 15 patients with a nondiagnostic bronchoscopy after TBNA and TBFB sampling underwent further diagnostics or follow-up to provide a classifying diagnosis in all patients .p = 0.016) and sarcoidosis . Among the other subgroups, the DY between the two procedures was similar , of which 18 were treated with topical use of vasoconstrictors. In two patients, there was respiratory failure requiring noninvasive ventilation in one case and hospitalization for observation in the other case.In this retrospective bicentric study, we tested for the DY and safety of EBUS-TBFB in addition to EBUS-TBNA as a complementary sampling technique using a 1.5 mm forceps for diagnostic tissue acquisition from mediastinal/hilar LAD or masses compared to standard EBUS-TBNA alone. We were able to demonstrate a significantly higher overall DY of the combined technique as compared to EBUS-TBNA alone in a large cohort of 105 patients. In the subgroup analysis, we found a significantly superior DY for the diagnosis of lung cancer and sarcoidosis. However, EBUS-TBFB was technically not feasible in a significant number of patients.Basically, it is not surprising that histological specimens yield higher diagnostic accuracy as compared to cytology. For this reason, video-assisted mediastinoscopy (VAM) is recommended according to the guidelines by the European Society of Thoracic Surgery (ESTS) when EBUS/EUS-TBNA remains nondiagnostic . HoweverIn a recent meta-analysis by Agrawal et al., the reported pooled DY of EBUS-TBNA was 67% and 92% when EBUS-TBNA was combined with EBUS-TBFB . CompareRegarding sarcoidosis, both techniques demonstrated a marginally lower DY for the diagnosis than reported in former studies ,17,18. TThe superior value of histological specimens compared to EBUS-TBNA cytology samples for the diagnosis of lymphoma has been reported recently . Yet, thAnother approach to provide tissue samples with greater volume in mediastinal lesions was proposed by Zhang et al. using transbronchial cryobiopsy performed under EBUS guidance . They reRegarding our secondary endpoint, EBUS-guided TBFB permits a safe lymph node or tumor biopsy through the bronchial wall with a favorable complication rate. EBUS-TBFB was generally safe, and no major complications occurred. This finding matches previous reported complication rates . Owing tIn addition to the retrospective study design, there were several limitations that need to be considered. Selection bias introduced by the exclusion of patients in which EBUS-TBFB was technically not possible to perform failed to ensure that our study sample is representative of the wider patient population with unknown hilar LAD or masses. Approximately 20% of the initially enrolled patients were excluded, mostly because of the inability of the forceps to pass the bronchial wall. Given that the 19-gauge needle was used for TBNA in approximately 80% of these cases, the results might imply a correlation between needle size and technical feasibility. However, the outer diameter of both needles is identical, and this supposition will require further study. Mehta et al. used a flexible electrocautery knife to create a tract for the forceps with a successful penetration of the bronchial wall [Compared to needle aspiration with an average sampling of three different lymph nodes per patient, only one was sampled by TBFB. Moreover, the fact that forceps biopsies were always conducted at the same location of the mass or lymph node resulted in the diagnostic accuracy of TBFB only being evaluated within one region of the lesion. Either way, TBFB may have missed diseased tissue, which we assume limits the diagnostic power of forceps biopsy.Although the results are in favor of better quality of EBUS-TBFB specimens compared to EBUS-TBNA specimens, we did not directly assess and compare specimen quality. This study did not clarify whether any advantage of EBUS-TBFB biopsies over EBUS-TBNA specimens exists regarding the amount and quality of tissue.In conclusion, our study demonstrated a safe and feasible technique for biopsy of enlarged mediastinal LAD or masses using a 1.5 mm mini-forceps in a large cohort with superior overall DY compared to EBUS-TBNA as a standalone technique. Among the subgroups, we found a significantly superior DY for the diagnosis of lung cancer and sarcoidosis. However, regarding the lower DY of EBUS-TBNA in lung cancer diagnosis in our own study compared to the current literature, the benefit of EBUS-TBFB might have been overestimated. Using an individualized patient approach based on preprocedural examination and imaging, we recommend the use of complementary EBUS-TBFB in mediastinal/hilar LAD or masses suggestive of sarcoidosis. However, technical issues are a major obstacle. A randomized study would be needed to investigate EBUS-TBFB in comparison to EBUS-TBNA and to upcoming techniques, such as transbronchial cryobiopsy.


About 11% of U.S. older adults are at risk for or have subjective cognitive decline. Although some factors that affect brain health cannot be changed, research indicates lifestyle changes  can delay or reduce cognitive decline. Drawing from existing research, UI Extension developed Wits Wellness, a 12-week program designed to enhance brain health among people ages 50 and older. Wits Wellness addresses multiple factors that affect cognitive health . Using a two-arm randomized control trial, 285 participants  were randomly assigned to the Wits Wellness intervention  or a waitlist control group. Summative program evaluation surveys indicated adherence to the intervention was high, with 68% of participants attending 9 or more of the 12 sessions. Program acceptability was high, with 82.7% evaluating the program as great to excellent, and 90.8% reporting great to excellent interaction with program leaders. Approximately 63.6% of participant write-in comments included positive statements about the program challenging their brains, and 59.1% indicated the program positively affected participants’ socialization. For program feasibility, 90.4% rated the 60-minute weekly sessions ‘just right’ for program length, while 66.3% rated the 12-week program duration ‘just right’ and 27.7% rated it ‘too long’. Thus, preliminary results suggest that Wits Wellness delivered both in-person and virtually was well attended and highly acceptable in the community setting. Future studies will examine the program’s efficacy in improving physical and mental health related outcomes.