In response to global interest in the development of a universal influenza vaccine, the Bill & Melinda Gates Foundation, PATH, and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of experts  to assess the role of a standardized controlled human influenza virus infection model (CHIVIM) towards the development of novel influenza vaccine candidates. This report (in two parts) summarizes those discussions and offers consensus recommendations. This article (Part 1) covers challenge virus selection, regulatory and ethical considerations, and issues concerning standardization, access, and capacity. Part 2 covers specific methodologic considerations.Current methods for influenza vaccine development and licensure require large costly field trials. The CHIVIM requires fewer subjects and the controlled setting allows for better understanding of influenza transmission and host immunogenicity. The CHIVIM can be used to identify immune predictors of disease for at-risk populations and to measure efficacy of potential vaccines for further development.Limitations to the CHIVIM include lack of standardization, limited access to challenge viruses and assays, lack of consensus regarding role of the CHIVIM in vaccine development pathway, and concerns regarding risk to study participants and community. To address these issues, the panel of experts recommended that WHO and other key stakeholders provide guidance on standardization, challenge virus selection, and risk management. A common repository of well-characterized challenge viruses, harmonized protocols, and standardized assays should be made available to researchers. A network of research institutions performing CHIVIM trials should be created, and more study sites are needed to increase capacity.Experts agreed that a research network of institutions working with a standardized CHIVIM could contribute important data to support more rapid development and licensure of novel vaccines capable of providing long-lasting protection against seasonal and pandemic influenza strains. Influenza is an ongoing public health challenge, causing significant worldwide morbidity and mortality. There is increasing global interest in the development of a universal vaccine that would provide broad long-lasting protection against both seasonal and pandemic influenza.Current seasonal influenza vaccines target specific virus strains by inducing antibodies to the head region of the viral hemagglutinin protein (HA). This region undergoes gradual antigenic changes over time - antigenic drift - which can reduce the efficacy of seasonal vaccines and requires updating vaccines semiannually to match evolving circulating strains. Due to their strain-specific design, current seasonal vaccines are less effective against novel or pandemic strains. A broadly protective “universal” vaccine would be capable of inducing immunity to multiple influenza type A and B viruses and would provide longer lasting protection against both seasonal and pandemic influenza.Research and technologic advances have resulted in the development of innovative vaccine strategies based on better understanding of the pathogenesis of influenza and host immunologic responses Human challenge trials (HCTs) may be a useful additional tool for development and evaluation of novel universal vaccines. HCTs require fewer participants and can be used to assess efficacy for more rapid selection of promising vaccine candidates. Due to their controlled nature, challenge trials can contribute to a detailed understanding of how immune responses to a vaccine candidate modify the outcomes of an exposure to a viral inoculum in terms of virus replication and symptoms of illness; this could define new CoPs. Current human influenza challenge models have some limitations, however. Certain artificial characteristics of current models  prevent them from adequately representing community-acquired infections (CAIs). (See “Route of Administration and Dose” in the companion article about CHIVIM methodology) The Bill & Melinda Gates Foundation (BMGF), PATH and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of approximately 60 experts  in LondoThis article (Part 1) summarizes the discussion and recommendations from four of the five topics covered at the convening, including realizing the full value of CHIVIM, selection of challenge virus strains, industry and regulatory perspectives, ethical considerations, standardization, and increasing capacity and access. The authors would like to thank the following panelists who shared their expertise: Bruce Innis, MD, PATH; Sean Tucker, PhD, Vaxart, Inc.; Kathleen Neuzil, MD, MPH, FIDSA, University of Maryland Center for Vaccine Development and Global Health; Jerry Weir, PhD, US Food & Drug Administration Division of Viral Products; Marco Cavaleri, PhD, European Medicine Agency Anti-Infectives and Vaccines Division; Diane Post, PhD, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Punnee Pitisuttithum, MD, DTMH, Mahidol University, Vaccine Trial Centre, Faculty of Tropical Medicine; Claudia Emerson, PhD, McMaster University, Institute on Ethics & Policy for Innovation; John Treanor, Tunnell Government Services; Florian Krammer, PhD, Icahn School of Medicine at Mount Sinai; David Wentworth, PhD, US Centers for Disease Control & Prevention; John McCauley, PhD, Francis Crick Institute, WHO Collaborating Centre for Reference and Research on Influenza; Othmar Engelhardt, Dr nat techn, National Institute for Biological Standards and Control; Emily Erbelding, MD, MPH, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Francesco Berlanda Scorza, PhD, PATH; Zoe Seager, PhD, Wellcome Trust; Marie Van Der Wielen, MD, GSK Vaccines; Saranya Sridhar, MD, PhD, MPH, Sanofi Pasteur; Jonathan Edelman, MD, Seqirus, Inc.; and Lidia Oostvogels, MD, CureVac AG. Recommendations reflect a “majority report” with panelists’ recommendations, as reflected in their slides and comments from the dais, and comments from the audience being reported. All panelists and participants had the opportunity to review and comment on a late draft of the meeting report. The companion article “Meeting Report: Convening on the Influenza Human Viral Challenge Model for Universal Influenza Vaccines, Part 2” provides a summary of CHIVIM methods discussed at the meeting, including subject selection and screening, route of exposure and dose, devices for administering challenge, rescue therapy, protection of study participants and institutions, and other methodologic considerations.11.The model should measure efficacy of potential vaccines against appropriate outcomes to more efficiently select candidates for field trials.2.The model should identify surrogates of broad protection as predictors of disease severity in at-risk populations and to optimize dosing3.The model should help accelerate development of pediatric vaccines4.The model should be useful for assessing the impact of vaccine candidates on shedding as a surrogate for transmission5.The model should assess duration of protection.This session focused on exploring the value of human challenge studies as a tool for vaccine development. The panel reviewed the World Health Organization (WHO) Preferred Product Characteristics (PPC) for Next-Generation VaccinesThe CHIVIM requires several key features to achieve these goals. It should induce disease that approximates natural infection in terms of severity, symptoms, and areas of respiratory tract involvement. The challenge virus route of exposure and dose should also simulate CAI. It must be standardized and reproducible, and most importantly, the model should control the risk of harm to study participants and the risk for introduction of novel strains into the community.1.1Early influenza vaccine HCTs in the 1940′s were performed using aerosol inhalation of influenza A or B as the challenge, which induced illness that resembled naturally occurring disease The largest recent influenza vaccine trial (179 participants) using a human challenge model (NCT02918006) evaluated the efficacy of a novel seasonal influenza virus vaccine candidate compared to a licensed quadrivalent vaccine and placebo. Study participants were screened for baseline HI titers ≤ 10 to ensure sufficient attack rates and received intranasal virus challenge. Despite low levels of pre-challenge immunity, participants experienced insufficient disease to confirm vaccine efficacy for either active treatment, although both vaccines reduced the risk of infection  in a post-hoc analysis. The study did identify individual immune CoPs for each vaccine. The trial was expensive due to the large recruitment requirements (to find participants with low HI titer) and containment costs.Human challenge models have been used in the development of many other vaccines including cholera and typhoid vaccines 1.2Industry experts agreed that CHIVIM could become a useful tool in the development of commercially-produced vaccines, especially if the model can assess the potential for broader protection. The model could also be effective for validating products that have new mechanisms of action, and for products that lack known CoPs. In the industry research pipeline, CHIVIM may be most useful for deciding whether or not to proceed with larger studies, rather than for down-selection between various candidate vaccines. CHIVIM studies could be conducted pre- and post-licensure as new and diverse challenge viruses become available to extend the evidence for broad protection.There was agreement that the model must be well-developed for industry needs and be predictive for prevention of clinically meaningful disease. The pathway to licensure of novel influenza vaccines will require demonstration that vaccination reduces the risk of disease, and the necessary trials will have to be large and conducted over several years to accrue sufficient evidence of broad and durable protection. Manufacturers will need to manage the risk of making these development investments by generating pre-clinical and early-stage clinical evidence supporting the effectiveness of their vaccine candidate. Experts noted that challenge virus stocks could have limited lifespans, and that investment of time and expense for the production of challenge viruses without assured market potential could be an issue. There was also concern about the risk for discontinuation of a product development program that is potentially viable against natural infection because of poor performance in a CHIVIM study.For industry, CHIVIM studies may play a role in the universal vaccine development process but must demonstrate value that is comparable to the time and investment required. A clear pathway to licensure for a potential universal influenza vaccine is needed in order for companies to be willing to invest in CHIVIM.2Regulatory experts agreed that well-characterized human influenza challenge models could contribute data that support regulatory approval of broadly protective influenza vaccine candidates. However, there is currently no consensus among regulatory agencies about the role of challenge models in vaccine approval pathways. There was agreement that the WHO should create harmonized guidance for influenza challenge trials intended to support universal vaccine approval, with input from the WHO Product Development for Vaccines Advisory Committee.Regulatory experts agreed that HCTs are best for evaluating efficacy (rather than safety) of candidate vaccines and could be an efficient way to select candidate vaccines for field trials. There was agreement that CHIVIM may be most useful for understanding immune CoPs and other markers, and for evaluating efficacy of vaccines intended to attenuate severity/length of disease by activating cellular immunity. It was noted that for CHIVIM to be effective in this role, it should induce illness with adequate intensity/duration that is not confounded by post-challenge antiviral therapy. In addition, the term “universal vaccine” is unlikely to appear in a product label, but challenge trials could provide evidence of broader protection against influenza that could be included in the prescribing information. Finally, CHIVIM studies alone are not likely to produce sufficient evidence of clinical benefit to support an accelerated product approval based on the current regulatory approaches.With regards to the ethics of human challenge trials, experts emphasized the importance of weighing any potential public health benefits against the risks associated with CHIVIM. There was agreement that more guidance is needed in this area, particularly with regards to assessing environmental risk. A proposed Zika HCT was not approved due to concerns about subject risk versus social benefit, and especially potential third-party risk US regulations concerning Dual Use Research of Concern (DURC)All agreed that identical ethical standards for HCTs should maintained when conducting research in low and middle-income countries (LMICs). Subject compensation can vary by location, as long as payments are non-coercive and study participants fully understand potential risk.3In order for CHIVIM to address multiple research questions, a full panel of well characterized challenge viruses is needed. The desired preclinical and clinical criteria for human influenza challenge viruses should be established, as well as consensus on preferred sources and production substrates . There are several important preclinical criteria for challenge viruses. They should be derived from an acceptable source ), and should be produced in a suitable production substrate and according to current Good Manufacturing Practice (GMP). They should exhibit genetic stability, and there should be no evidence of adventitious agents. Finally, challenge viruses should be susceptible to available antiviral therapies. Clinically, challenge viruses should induce moderate, overtly symptomatic, uncomplicated disease that can be confirmed by detection of influenza virus replication, with complete recovery in healthy participants. Safety, established through trials, should be an important criterion for virus selection.Currently there are several H1N1 as well as H3N2 challenge strains that have been used in recent studies.  Additionin vitro testing would support an inference of broad protection.It was suggested that multiple strains of the same influenza A subtype may be needed in order to adequately challenge a broadly protective vaccine. If a candidate vaccine elicits antibodies that target the HA “stem” region of H1N1 or H3N2 and is found to be protective, demonstration of similar anti-HA stem responses to other influenza A subtype viruses in the same phylogenetic group by 3.1Using contemporary influenza virus strains as challenge agents is the most feasible approach from a risk management perspective, but many study participants would have immunity resulting in low infectivity. However, younger adult participants should be more susceptible to historical strains that are no longer circulating, which could facilitate subject recruitment, increase attack rate, and induce more overt illness and/or greater virus shedding. Historical strains may serve as a better test for broadly protective candidate vaccines and should have a longer period of viable use . Historical antigenic drift isolates that emerged but failed to persist were suggested as an attractive subset of historical strains to be considered. Regardless, the risk of historical strains escaping into the community is of concern, and the value of available influenza vaccines to protect staff or contain a community outbreak may be limited.Due to cross-reactivity between current circulating strains and many historical H1N1 strains, young adults aged 18–30 should have increased susceptibility to H1N1 viruses that circulated exclusively between 1977 and 1984. RG could be used to derive the most promising strains from that period, using wild type and A(H1N1)pdm09 variants as backbone, and potentially including a suicide mechanism. A historical approach to define antigenically distant H3N2 and influenza B challenge agents could be used as well.There was noted consensus among the panelists that H2 influenza strains, though possibly well-suited for evaluating pandemic vaccine candidates for immunogenicity or for protection in animal models, should not be used as a challenge agent due to the risk of re-introduction into the mostly naïve (those born after 1968) community.3.2There are existing tools that could be adapted for assessing the safety of using historical strains as challenge agents for candidate universal vaccines. The Centers for Disease Control and Prevention Influenza Risk Assessment Tool (IRAT)The WHO Tool for Influenza Pandemic Risk Assessment (TIPRA)The panel discussed potential strategies for producing RG challenge viruses with safety features  that could mitigate risk to the community should the virus escape containment.The WHO has guidelines for clinical trial design that can help to reduce environmental risk, such as using personal protective equipment (PPE) 3.3The WHO Global Influenza Surveillance and Response System (GISRS) is a network of research centers and laboratories in more than 100 countries that work together to sample and evaluate circulating influenza virus strains. Six WHO Collaborating Centers (CCs) isolate and sequence new influenza variants, as well as perform detailed antigenic analysis and antiviral sensitivity testing. Candidate vaccine viruses are propagated in eggs and in qualified cell lines (following standard operating procedures (SOPs)), and the list of available viruses is updated every six months. Adventitious testing is the responsibility of vaccine manufacturers. These WHO CCs are therefore well situated to perform a similar role for the selection of candidate challenge viruses.The need for an available cell line for production of challenge viruses and the lack of necessary reagents was discussed. Once a process for strain selection is established, it is recommended that a government agency such as the National Institute of Allergy and Infectious Diseases (NIAID) or non-profit produce the challenge viruses in a dedicated cell line, using standardized reagents and protocols. NIAID is currently funding the production of H1N1 and H3N2 challenge strains, and has agreed to make them available to the extramural research community. Challenge strains produced in the US could be used in other countries, although a Material Transfer Agreement may be required in some cases. Extensive adventitious testing of any potential challenge strain would be necessary.44.1Standardization of CHIVIM assays and clinical protocols is needed for reliability and comparison of results between researchers and institutions. Some approaches to improving standardization of assays between research laboratories include assay harmonization, use of biological standards, proficiency testing of labs, and centralized testing. Studies on inter-laboratory variability using harmonized assay protocols have shown mixed results, although detailed protocols with specific parameters are more useful than general recommendations Harmonized study protocols have been successfully developed and implemented for clinical trials. One issue for influenza vaccine challenge trials is the need for comparator vaccines. As the susceptibility of any study cohort to a particular challenge virus is likely to vary from trial to trial, using a licensed seasonal influenza vaccine as a control treatment in addition to a placebo-treated group would provide useful context by enabling an assessment of a vaccine candidate’s efficacy relative to the current standard of care as well as relative to no vaccination.There are several consortia that support collaboration between researchers and institutions working on influenza vaccines. The CONSISE consortium 4.2The four institutions that are currently conducting CHIVIM studies  produce their own challenge virus strains using specific manufacturing and quality controls. In order to create more access to challenge viruses and improve standardization, a common repository of challenge viruses is needed. WHO could provide guidance on strain selection, as discussed above.4.3The need for more CHIVIM studies will depend on the number of candidate vaccines in development. Standardization of the model and access to materials will facilitate the creation of new study centers to increase capacity as needed. Although influenza challenge trials are currently limited to European countries and the US, there may be advantages to conducting these trials in LMICs as well, particularly in places with increased genetic diversity and/or less established immunity from routine influenza vaccination, and to build vaccine development capacity in low-resource communities where the burden of influenza may be most profound.When conducting studies in LMICs, there are some additional factors to consider, such as the time necessary to achieve adequate community engagement, informed consent and appropriate compensation, infrastructure limitations and ensuring adequate containment of challenge virus, and whether the investigational product will become accessible to the population.5Goal: Universal influenza vaccine licensure(1)Standardize the modelThe ultimate goal for CHIVIM is to accelerate the accumulation of knowledge needed to develop and license broadly protective influenza vaccines offering long lasting protection against both seasonal and pandemic disease.(2)Manufacturing of challenge virus stocksThe issue of standardization was a recurring theme during the discussions, particularly with regard to the effectiveness of CHIVIM as a tool for vaccine development. Standardization of the model is critical to produce meaningful, comparable results from CHIVIM trials that can support universal vaccine licensure. The list of CHIVIM components that require standardization is extensive and includes challenge virus production and release procedures, reagents, trial protocols, assays, route of challenge administration and delivery methods, rescue protocols, safety protocols, and comparator vaccines. WHO and other key stakeholders including regulatory agencies and industry should collaborate to develop harmonized guidance on the standardization needed to make CHIVIM a more precise tool.Selecting and producing appropriate challenge viruses may be the rate-limiting step in the realization of CHIVIM. Currently there is a limited number of available strains and lack of guidance for the selection and production of challenge virus. Challenge viruses must be well-characterized and matched to the research questions being investigated. To this end, the recommendation is for WHO to take the lead on the selection of strains and evaluation of seed stocks, taking into consideration the desired preclinical and clinical characteristics for influenza challenge discussed above. WHO should also provide guidance on GMPs that are specific to influenza challenge virus strains.Special consideration and consensus are needed for the issue of using historical influenza strains, viruses produced with reverse genetics, LPAI strains, or other controversial challenge viruses to address particular research questions.(3)Mitigate RiskAll well-characterized influenza virus challenge agents should be made available to qualified institutions for CHIVIM trials.(4)Create a research network and refine the objective measures of influenza diseaseExperts agreed that safety should be the primary consideration when designing CHIVIM trials. A WHO white paper addressing the assessment and mitigation of risks associated with CHIVIM is needed. Risk mitigation strategies should be standardized and address all potential risks to study participants, staff, and community.(5)Expand Access and CapacityA research consortium should be created for institutions conducting CHIVIM trials for universal vaccine development, allowing for the free exchange of resources, best practices, and data between participating members. Challenge viruses, harmonized protocols, and standardized assays should be made available to all CHIVIM study sites. As the clinical syndrome following influenza virus challenge is anticipated to be mild, refined objective measures of illness and altered airway function should be devised to assess the benefit of vaccination.(6)Assess Results and Further Develop CHIVIM as NeededThe number of research centers performing challenge studies for universal vaccine development should increase. The research consortium network and standardization of the model will facilitate an increase in capacity. Expansion to LMICs is recommended where feasible, with special attention to ensuring adequate containment, community involvement, and informed consent.As these steps are taken and the results from CHIVIM studies become available, further refinement of the model may be necessary. Novel vaccine mechanisms, further understanding of immune response, or other new information may provoke research questions that will require modifications to the model.All authors attest they meet the ICMJE criteria for authorship.


Inappropriate complementary feeding practices significantly contribute to undernutrition among children under 2 years of age in India. However, there is limited up-to-date evidence on the prevalence and factors associated with complementary feeding practices to guide policy actions at the subnational level in India. We investigated the regional prevalence and factors associated with complementary feeding practices in India.n = 8469), South , East , West (n = 8940), North-East (n = 2422) and Central . Factors associated with complementary feeding by region in India were investigated using logistic regression Generalized Linear Latent and Mixed Models (GLLAMM) with a logit link and binomial family that adjusted for clustering and sampling weights.This study used a sample of 69,464 maternal responses from the 2015–16 National Family Health Survey in India. The prevalence of complementary feeding indicators was estimated using data for each administrative region, namely: North  among infants aged 6–8 months in regional India; highest in the South (61%) and lowest in the Central and Northern regions (38%). Similarly, minimum dietary diversity (MDD) was highest in the South (33%) and lowest in the Central region (12%). Both minimum meal frequency (MMF) and minimum acceptable diet (MAD) varied substantially across the regions. The factors associated with complementary feeding practices also differed across Indian regions. Significant modifiable factors associated with complementary feeding practices included higher household wealth index for the introduction of complementary foods in the North and Eastern India; higher maternal education for MMF and MDD in the North and Central regions; and frequent antenatal care visits (≥4 visits) for all indicators but for different regions.Our study indicates that there are wide differences in regional prevalence and factors associated with complementary feeding practices in India. The improvement of complementary feeding practices in India would require national and sub-national efforts that target vulnerable mothers, including those with no education and limited health service contacts. Globally, childhood undernutrition is a major public health issue, particularly in developing countries . In 2016Appropriate complementary feeding is not only essential for child growth but also provides the foundations required for good health throughout life . EvidencPrevious nationwide studies conducted in India that utilised the 2005–2006 India Demographic and Health Survey (DHS) reported that limited access to health services, low socioeconomic status and no or low maternal education were associated with inappropriate complementary feeding practices . The fin. The present study aimed to investigate the prevalence and factors associated with complementary feeding practices by region in India.To the authors’ knowledge, no past studies have provided a detailed regional analysis of the prevalence of complementary feeding practices, nor has there been an investigation of factors associated with complementary feeding outcomes by region based on the most recent nationally representative data for India (2015–16 India DHS). A detailed regional analysis is needed in India, given the significant disparities in the socioeconomic indicators in the country which has been shown to influence child health and nutritional status , 11. TheThe overall methodology used in this study has been described elsewhere . Brieflyn = 8469), South , East , West (n = 8940), Central  and North East (n = 2422) regions. The northern region consists of Jammu and Kashmir, Himachal Pradesh, Haryana, Delhi, Chandigarh, Punjab and Rajasthan. Southern region consists of Andaman and Nicobar Islands, Andhra Pradesh, Karnataka, Kerala, Lakshadweep, Puducherry, Tamil Nadu and Telangana. Eastern region consists of Bihar, Jharkhand, Odisha and West Bengal. The western region consists of Gujarat, Maharashtra, Goa, Daman and Diu as well as Dadra and Nagar Haveli. The central region consists of Chhattisgarh, Madhya Pradesh, Uttar Pradesh and Uttarakhand. The north-eastern region consists of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim and Tripura. The distribution of states into regions was performed by the Government of India to facilitate allocation of funds for administrative purposes and improvement of inter-state cooperation [A total of 69,464 maternal responses for children aged 6–23 months were selected for the survey and were assessed based on the WHO specified complementary feeding indicators. The children were from six administrative regions, namely: North : The proportion of infants 6–8 months of age who received solid, semi-solid or soft foods.Minimum dietary diversity (MDD): The proportion of children 6–23 months of age who received foods from 4 or more food groups. The 7 food groups used for tabulation of this indicator were: grains, roots and tubers; legumes and nuts; dairy products ; flesh foods , eggs, vitamin-A-rich fruits and vegetables; and other fruits and vegetables.Minimum meal frequency (MMF): The proportion of breastfed and non-breastfed children 6–23 months of age, who received solid, semi-solid or soft foods (including milk feeds for non-breastfed children) the minimum number of times or more . “Meals” include both meals and snacks , and frequency is based on caregiver report.Minimum acceptable diet (MAD): The proportion of children 6–23 months of age who received both minimum dietary diversity and minimum meal frequency. All other indicators were based on a 24-h recall of the infant’s dietary intake by the mother.The assessment of the study outcomes (primary variables) followed the WHO definitions for assessing IYCF indicators in a population .IntroducThe explanatory variables were categorised into child, maternal, household, health service and community level characteristics for each region. The characteristics of the child included sex, age, the perceived size of the baby at birth, preceding birth interval and birth order of the child. For the mother, the characteristics included maternal age, education/literacy level, employment status, power over earnings, power over household purchases, as well as the type of caste or tribe and religion.For the family or household level characteristics, marital status, household wealth index, and access to media sources like newspapers, radio, and television were considered. The household wealth index was derived from a principal component analysis conducted by the IIPS and ICF International and was calculated as a score of ownership of household assets such as transportation device, ownership of durable goods and household facilities. The IIPS and ICF International classified the household wealth index into five categories (quintiles), and each household was assigned to one of these wealth index categories, namely; poorest, poorer, middle, rich and richest . In addiThe analytical strategy was similar to previously published studies , 17, 18.Specifically, a five-stage modelling methodology was used in the multivariable analyses. First, in modelling of child factors, adjustment for maternal, household, health service and community factors was conducted in the assessment of child factors associated with complementary feeding practices by region in India. We used a similar approach for maternal, household, health service and community factors in the third, fourth and fifth stages, respectively. Adjusted odds ratios (aORs) and their corresponding 95% confidence intervals were calculated and reported as the measure of association between the study factors and complementary feeding practices for each Indian region. All analyses were performed in Stata version 14.0 .Across all regions in India, about 80 % of mothers were aged between 25 and 34 years. The majority of mothers in the Central region practised Hindu religion (83.5%) while the religion was the least practised among mothers in the North-Eastern region (46.6%) Table . North-ESouthern region had the highest prevalence of complementary feeding among infants aged 6–8 months compared with other regions. Both Southern (33%) and North-Eastern (29%) regions had better MDD prevalence among children aged 6–23 months compared with other regions, whereas the Central region had the lowest prevalence 12%)  visits were associated with the introduction of complementary foods to infants of mothers from the Eastern and Central regions. Mothers who had at least four ANC visits were more likely to introduce complementary foods and have children who were more likely to meet the MDD compared with mothers who had no ANC visits. These findings may be attributed to a number of factors relating to non-use of ANC, including low maternal education, the cost associated with attending ANC service and a lack of awareness of the importance of ANC among mothers –34. SimiThe present study showed that approximately 16% of mothers received assistance from a health professional during delivery. The small proportion of mothers who received skilled-assisted delivery compared to previous regional reports (50%) , is possAnother finding of this study was that children in higher birth order (second and above) were more likely to be introduced to complementary feeding compared with those in the first-birth order, irrespective of the Indian region. A previous study conducted among Ethiopian women found significant associations between higher birth order and MDD . Similar. Our study findings imply that IYCF policy and interventions should also focus on younger mothers who are likely to be primiparous women with little experience in IYCF practices.The study indicated that higher maternal age (≥25 years) was associated with complementary feeding practices, with variations across the regions in India. Specifically, while older mothers were less likely to introduce complementary foods to their infants in the West and Central regions, Northern and Central, older mothers were more likely to have infants who met the MDD and MAD compared to younger mothers (< 25 years) in those regions. Such significant effects of maternal age on complementary feeding suggests that the mother’s experience may play a significant role in appropriate IYCF practices. Our findings are consistent with evidence from Nepal which indicated that children of older mothers ≥35 years) were more likely to meet MDD and MAD compared with children of younger mothers (< 20 years) [ years weThe present study also indicated that women autonomy over household earnings and power over household purchases were associated with complementary feeding practices, with demonstrable regional variations across India. Specifically, our study demonstrated that children of mothers who had power over household earnings and decision making were more likely to meet MMF compared to their counterparts from Central India. Similar findings were observed in the Southern region for MDD. These results may be attributable to high maternal education, the freedom to exchange information and interact with other people outside of the family at social gatherings or markets and exposure to media , 46. AlsVarious methodological limitations need to be considered when interpreting the study results. First, the information on the survey was based on interviews and subjective responses from mothers, and the results may be affected by recall bias. However, the analyses were restricted to the most recent child, alive and living with the respondent to reduce the potential effect of recall bias on the observed association. Second, the number of ANC visits were recalled by the mother who may have underestimated or overestimated the actual number of ANC visits. This may lead to a possible measurement misclassification bias, with subsequent under- or overestimation of the association between frequency of ANC visits and complementary feeding practices. Third, we were unable to assess all potential confounding factors . This may have an impact on the association between the exposure and outcome variables. Lastly, the establishment of temporal association in this study is impossible given the use of cross-sectional data, where both the exposure and outcome variables were collected concurrently.Despite these limitations, the study has strengths. Our study used the most recent and nationally representative data (NFHS-4) for India. The NFHS-4 data were obtained from a larger sample compared to previous national surveys, indicating that our findings are more representative of the Indian population in guiding up-to-date and evidence-based policy interventions. The data used are comparable across regions in India given that they were collected by trained personnel who used standardized questionnaires and methodology. The study findings are unlikely to be affected by selection bias as the survey yielded high responses rates, over 94%.The study found regional variations in prevalence and factors associated with complementary feeding indicators across India. Southern region followed by the North Eastern region had a higher prevalence of complementary feeding practices compared with other regions. Mothers with higher education, those from wealthier households and mothers who made frequent ANC visits were more likely to have appropriate complementary feeding practices compared with mothers with no schooling, those from poorer households and mothers who made no ANC visits across Indian regions. This study suggests that efforts to improve complementary feeding practices must be context-specific and should target mothers with vulnerabilities, including those from poorer socioeconomic backgrounds and no ANC visits. Findings from this study would assist policy decision-makers and public health managers in resource allocation to improve complementary feeding practices in India.


OBJECTIVES/SPECIFIC AIMS: Explore perceptions of Flint stakeholders on the water crisis regarding trust and the capacity of faith and community-based organizations providing public health services to address community needs. Analyze the community’s voice shared at (1) 17 key community communications , and (2) during 9 focus group sessions, in which residents, faith-based leadership and other stakeholders discuss issues and concerns on the Flint Water Crisis, and recommend ways to address them. Develop a framework that defines core theories, concepts and strategies recommended by the community to help rebuild trust and the quality of life in Flint, Michigan, and support other communities experiencing environmental stress. METHODS/STUDY POPULATION: Study population: faith-based leaders, seniors, youth, Hispanic/Latino and African American stakeholders, and others experiencing inequities in the city of Flint. Convene 9 focus group sessions (recorded and transcribed) to learn community perceptions on trust and ways to address it. Validate accuracy of the transcriptions with community consultants to reconcile any inaccurate information. Through a community engaged research (CEnR) process, review and analyze qualitative data from the 9 focus group sessions, and quantitative data from 2 surveys documenting (1) demographic backgrounds of focus group participants, and (2) their perceptions on trust and mistrust. Prepare a codebook to qualitatively analyze the focus group data summarizing community input on trust, mistrust, changes in service delivery among community and faith-based organizations, and ways to re-build trust in the city of Flint. Transcribe the community’s voice shared during 17 key events, identified by a team of community-academic stakeholders , in which residents and other stakeholders discuss issues and concerns on the Flint Water Crisis, and recommend ways to address it. Qualitatively analyze the transcriptions, using a CEnR process to prepare a codebook on key themes from the community’s voice shared at these events, and recommendations on ways to address it. Compare and contrast findings between the two codebooks developed from (1) the focus group data and (2) qualitative analysis of community voice during public meetings and events. Synthesize this information into a framework of core theories, concepts and rebuilding strategies for Flint, Michigan. RESULTS/ANTICIPATED RESULTS: It is important to note many undocumented immigrant populations in Flint fear deportation and other consequences, hampering their ability to obtain service and provide community voice. Through our purposive sampling approach, we will hear from community voices not often included in narratives . The presentation will present findings documenting levels of trust and mistrust in the city of Flint; and a framework of recommendations, core theories and concepts on ways to reduce, rebuild and eliminate stress that will be helpful to other communities experiencing distress. DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge, levels of trust and mistrust in Flint have not been documented thus far. We will compare and contrast common themes presented by the community at public meetings and events with themes presented in our focus group effort on trust. Faith and community-based providers were among the first responders to the Flint Water Crisis. The effort will also share perceptions on changes in public health service delivery, and observations on preparedness for these roles that occurred among community and faith-based providers. Finally, the effort will (1) support the design of a research agenda, (2) define a framework of core theories, concepts and recommendations developed by the community to help rebuild trust in Flint, Michigan; and (3) support other communities addressing environmental distress.


Trace elements play a pivotal role in Colorectal Cancer (CRC) inhibition and development process. This systematic review provides the basic comparison of case-control studies focusing on concentration of trace elements between those with CRC and controlsth June 2017. The search strategy focused on Population, Intervention, Comparison, and Outcomes (PICO). We searched the role of trace elements in cancer and focusing on case-control studies in CRC to obtain an insight into the differences in trace element concentrations between those with and without cancer.The systematic review searched through two databases of Medline and Cochrane up to 24The serum concentrations of Ca, Cu, Mg, Mn, Se, Si, and Zn were lower in CRC patients but for Co and S the levels were higher in CRC patients. The concentrations of Cd, Cr, Cu, Mg, Mn, Pb, and Zn were increased in patients with metastasis, but not in Se. As for colon tissue specimens, inconsistent levels were reported between studies, notably in Cu, Se, and Zn. No changes were reported for B and Ca levels. Most of the trace elements in the tissue specimens showed higher concentrations of Cr, Fe, K, Mg, P, Rb, S, and Si compared to Br.With the growing interest to understand the link between trace elements in carcinogenesis and the possible interactions, multi assessment analysis of a larger cohort of samples is necessary. Colorectal cancer (CRC) incidence rates and trends contributed to the significant variation that occurs between geographical regions and across nations. Globally, CRC is the third most common cancer in adult males and second among females , 2. In AThe accumulation or deficiency of these elements may stimulate an alternative pathway towards the development of CRC. Several trace elements are considered as chemical carcinogens that may change the biological processes and induce carcinogenic effects , 20. TheOur immune system is the most common and natural defense mechanism against cancer that orchestrates the function of phagocytosis, complement system, lysosomes, immunoglobulins and interferons upon abnormal cell transformation. Reinforcement on this defense system in response to malignancy by the presence of trace elements such as zinc (Zn), selenium (Se) and manganese (Mn) has been reported previously –29. The We performed a systematic review on the role of trace elements in cancer and focusing on case-control studies in CRC to obtain an insight into the differences in trace element concentrations between those with and without cancer.We adopted the process of conducting a systematic review as outlined by the Cochrane Collaboration  and the th June 2017, and our search was limited to English-language publications. The search was performed based on the PICO: Population (CRC), Intervention (not related with current search), Comparison  and Outcome (trace elements level). The following search strategy was applied: colorectal adj1(carcinoma* or tumo? r* or cancer* or neoplasm*).tw OR colon* adj1(cancer* or neoplasm*).tw OR cancer adj3(colon*).tw OR sigmoid* adj1(neoplasm* or cancer*).tw OR cancer adj3(sigmoid*).tw OR sigmoid colon adj1(neoplasm* or cancer*).tw OR rectal adj1(tumo?r* or cancer* or neoplasm*).tw OR cancer adj3 (rectum*).tw OR rectum adj1(cancer* or neoplasm*).tw AND Biometal*.tw OR trace adj1(element*).tw OR micronutrient*.twTwo databases were searched, i.e. Medline and Cochrane Databases up to 24The title and abstract of articles were first screened from the initial search, followed by a review of the full-text articles of potentially eligible studies for further selection. The list of citations from the shortlisted articles was scanned for potential missing studies. The retrieved list of articles was carefully examined to exclude possible duplicates or overlapping information. Two reviewers assessed the full-text article independently by using a specific data extraction form. Studies were eligible for inclusion if trace element concentrations were measured in both colorectal cancer patients and healthy controls. Only studies that measured trace element status in colon tissue or serum with more than one trace element were included. In addition, only articles that reported a case-control study design were reviewed in their full text. Disagreements arose over 6% of the articles (κ=0.89) and this was resolved by discussion among reviewers and a third party.A standardized data extraction tool and a study quality grading instrument were developed. One reviewer extracted the data while the other reviewer checked the information for accuracy. Data extracted from each study include the information on the first author, year of publication, country, patient characteristics  and concentration of trace elements. Study quality was based on our own tool mainly adopted from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) risk of bias assessment for observational studies . The stuOut of the 129 publications identified, seven articles were relevant and one additional article was identified through the citation list of published work . Four arThe sample size of colorectal patients analyzed within each of the selected studies ranged from 11 to 76. The average age ranged from 45 to 85 yr old and the majority of the patients were female (68%). Most of the cases were of Dukes’ B stage and most of the studies involved hospital-based patients. The main exclusion criteria for case and control are patients with history of polyps, inflammatory bowel disease, and concurrent cancer.Atomic Absorption Spectrometry (AAS) application was the most popular acquisition used in these studies, accounting up to 62%. As for the concentration in colonic tissue specimens, inconsistent results were reported between studies namely on Cu, Se and Zn elements whereas B and Ca did not differ between colorectal and non-colorectal patients. Most of the trace elements in tissue specimens showed higher concentrations including Cr, Fe, K, Mg, P, Rb, S and Si.The knowledge gap that we aim to fill from this systematic review is to address the possible association between trace elements and colorectal cancer. From the extracted data, inconsistent concentrations of trace elements reported for the sera and colon tissues were noted between the studies. The variation is expected as different instruments were used for measurement and acquisition, hence the inevitably varied detection limits and readings. This variation is more pronounced in studies using tissue specimens compared to those which measured the serum and thus, necessitates the control of contamination. The issue of contamination issue has been flagged as a big concern for tissue sample analysis as compared to blood . IrreproHere, we highlight several important elements associated with human health and cancer. From our review, CRC patients generally showed an increased level of Cobalt (Co) and Sulphur (S) in their serum. Co is an important component in vitamin B12 and essential for human wellbeing . A higheZn is a vital element playing major roles in DNA synthesis, gene expression, various enzymes activities and maintenance of normal human growth . As partSelenium (Se) is a key element in several seleno-proteins that are essential for good health such as glutathione peroxidase (GPx)  In the fCu is the main building block for more than 30 enzymes in the human body including ceruloplasmin, ascorbate oxidase, lysine oxidase, dopamine-hydroxylase, cytochrome oxidase and tyrosinase . MobilizThere were no significant changes reported for Boron (B) and Ca from our extracted data probably due to unadjusted values in relation to different environmental exposure such as smoking and diet . Previou2+ has been reported to confer a metabolic advantage to the neoplastic cells in addition to causing the alteration in the genome , also known as lead, is presumed to be via the interference with the DNA repair processes . Pb-induAnimal and plant food products are the main sources of cadmium (Cd) in our body . The carMethyl bromide is a component of Bromine (Br) which is highly effective as a fumigant and is widely used in pesticides. The epidemiological and toxicological evidence had suggested a potential relationship between the exposure of methyl bromide and severe human health problems, including cancer . HoweverOur systematic review has revealed the limited data and lack of standardized assessment on environmental exposures  linked to the levels of trace elements in our body. This inadequacy contributes to the inconsistent results which may be due to unadjusted values with different levels of exposures. Evidence has implied the influence of these exposures onto the concentration of trace elements. Different levels of physical activity  weight cThe majority of the previous studies focused more on metal-induced carcinogenicity and lacked the approach of a multi-element assessment. Research on heavy metals has generally established the linkage to cancer either at higher or lower concentrations. There is still a need to study other elements as they may be the potential biomarkers for early detection of cancer or further developed as chemopreventive agents. However, many phases of discovery research and validation studies must be conducted before any cutoff values can be established. The need to investigate the role of these trace elements in a cohort setting cannot be disregarded in order to classify them as a definite risk factor and not just an association. With the advancement of technology in modern instruments with greater sensitivity, specificity and high-throughput capability such as the ICP-MS will certainly enable researchers to do more screening and group profile studies.Likewise, the interaction between the trace elements also needs to be explored further. Oxidative stress, antioxidants and trace element levels should be measured simultaneously to provide further insight into their central roles particularly in the mechanisms of carcinogenesis. This can be scientifically addressed by conducting in vitro and in vivo studies. Genomic research may also provide clues on how genetic polymorphisms and mutations may impact on the trace elements and their biological functions.Differential levels of trace elements were demonstrated in both serum and tissue samples of CRC patients as compared to healthy controls. Both deficiency and excess of trace elements are potentially harmful to patients and may be related to CRC development. In this systematic review, limited databases were searched due to institutional’s limited access, therefore the exploration may be incomprehensive.Ethical issues  have been completely observed by the authors.


Populations are aging locally, nationally, and globally – and challenging institutions of higher education to consider how they can respond to these changing demographics through new approaches to teaching, research, and community engagement. The Age-Friendly University (AFU) initiative was recently launched by an international team convened by Dublin City University, and endorsed by the Academy for Gerontology in Higher Education (AGHE). The AFU concept and 10 guiding principles provide a guiding campus-wide framework that colleges and universities can use for distinguishing and evaluating age-friendly programs and policies, as well as identifying institutional gaps and opportunities for growth. To date, over 45 institutions have joined the AFU global network. This presentation will describe how collaborations across aging-focused programs and campus units devoted to diversity, community engagement, professional studies, and related educational efforts offer prime opportunities to build and sustain an AFU vision.


Financial inclusion is an area of growing global interest in women’s empowerment policy and programming. While increased economic autonomy may be expected to reduce the prevalence of intimate partner violence, the mechanisms and contexts through which this relationship manifests are not well understood. This analysis aims to assess the relationship between women’s financial inclusion and recent intimate partner violence using nationally-representative data from 112 countries worldwide. Levels of both financial inclusion and recent intimate partner violence varied substantially across countries , and across regions. In multivariate global analyses, increased levels of women’s financial inclusion were associated with lower levels of recent intimate partner violence after accounting for asset-based enablers of economic autonomy and gender norms; this relationship was lost upon the inclusion of measures of national context . These results underscore that the relationship between financial inclusion and recent intimate partner violence is complex, follows many pathways, and is affected by context. In low and middle income countries, asset-based enablers of economic autonomy, gender norms and national context explained much of the relationship between financial inclusion and recent intimate partner violence. In those low and middle income countries with high levels of controlling behavior by male spouses, financial inclusion was associated with higher levels of recent intimate partner violence. These findings further suggest that initiatives that aim to prevent intimate partner violence by way of increased economic autonomy may be ineffective in the absence of broader social change and support, and indeed, as seen in countries with higher levels of men’s controlling behavior, backlash may increase the risk of violence. Efforts to improve women’s financial inclusion need to recognize that its relationship with intimate partner violence is complex, and that it requires an enabling environment supportive of women’s rights and autonomy. Nearly one in five women globally 19%) have experienced sexual or physical violence from an intimate partner in the past year, with wide variations in prevalence across countries 9% have e. There hBoth preventing IPV and expanding women’s economic autonomy have become prominent features in the global goals and policy agenda , 4. WhilThere is evidence suggesting that the ability to exit an abusive relationship, which may be facilitated by augmented economic autonomy, can deter further IPV. For example, state level family law reforms facilitating divorce in the United States reduced the risk of marital violence . In contFinancial inclusion, encompassing both access to and use of appropriate financial services, is emerging as a focal area of efforts to increase women’s economic autonomy . FinanciTo date, there is limited research exploring the relationship between financial inclusion and IPV, though evidence from India suggests that bank account ownership is associated with reduced risk of IPV . Women’sThe majority of theoretical models examining factors affecting IPV have used the ecological model to look broadly at risks from an individual up to a societal lens –25. ThisThis paper thus aims to address the gap in knowledge connecting the role of financial inclusion and risk of IPV. Specifically, we assess, for a large and diverse sample of countries, whether women’s financial inclusion–defined as having an account  at a bank or another type of financial institution or personally using a mobile money service in the past 12 months—is associated with lower levels of recent IPV, accounting for key contextual, normative and enabling factors.This study is an ecological analysis of the relationship between financial inclusion and IPV using publicly available, cross-sectional, country-level data from multiple sources see . We drewFinancial inclusion data was drawn from the World Bank’s Global Findex database, which compiles data collected from nationally representative triennial surveys  of individual financial behavior collected by Gallup, Inc.Employment rates come from ILOSTAT , in whicEmployment norms and cell phone use were taken from the 2015 Gallup World Poll, via reports from Gallup/ILO and the Women, Peace and Security Index , 29. CasHuman Development Index (HDI) values for the year most closely matched to the year of recent IPV data for (2005–2017) were taken from the United Nations Development Programme . The HDIData were extracted in March 2019.The sample was limited to the 112 countries with data on recent (past 12-month) IPV, as well as financial inclusion, of which 33 are defined by the World Bank as high income see  38]..38].Measure definitions and sources are shown in Financial inclusion is defined as the percent of women aged 15 or older who reported having an independent or joint account at a bank or another type of financial institution, or personally using a mobile money service in the previous 12 months.We grouped the covariates into three domains: (1) asset-based enablers of economic autonomy, (2) gender norms related to women’s lower status and control and (3) national context. Variables in (1) included paid employment, cash earnings, cell phone use and education. Variables in (2) included inequitable employment norms, decision-making over own earnings, controlling behavior and justification for wife-beating. Variables in (3) included HDI, fragile state status and region.All measures except HDI, fragile state status and region are derived from individual-level data and expressed as national prevalence estimates.Descriptive analyses included frequency statistics for all variables, overall and by region.We first assessed the relationship between independent variables and recent IPV using bivariate and multivariate fractional logit generalized linear models, to account for the bounded nature of the outcome (recent IPV). Full-sample regressions were modelled using sequential variable inclusion by measure grouping .We also modelled limited-sample regressions excluding high-income countries in order to include variables with limited geographic availability . All regressions included robust standard errors clustered at the regional level, and multivariate models adjusted for IPV year fixed effects.All datasets used contained only country-level, de-identified data.Globally, the median prevalence of recent physical and/or sexual violence in assessed countries was 9% , rangingThe median prevalence of financial inclusion was 39%, with near saturation in high-income countries, and only 21% median prevalence in Western Asia and Northern Africa. Across the global sample, the prevalence of women’s employment was 54%, ranging from a regional high of 70% in Sub-Saharan Africa to 23% in Western Asia and Northern Africa. Cell phone use was high in the total sample (82%) and women had a median of nearly nine years of education.Among indicators of gender norms, inequitable employment norms were highest in Central Asia and Southern Asia (28%) and West Asia and Northern Africa (26%).Most countries had high levels of female participation in decision making regarding their own earnings . However, more than one-half of women (65%) across assessed countries reported controlling behavior by partners . The median level of beliefs that wife beating was justifiable was 37% and of the sampled countries.HDI was highest among high income countries (median of 0.89) . Sub-SahIn bivariate analyses, women’s financial inclusion was negatively associated with recent IPV; for every 10% increase in financial inclusion, there was a 2% decrease in recent IPV . InequitIn multivariate analyses, there was a significant, negative association between financial inclusion and recent IPV in models adjusted for measures of economic autonomy and gender norms . Model 3Recognizing that high-income countries are distinct from others in our sample, characterized by lower levels of IPV and close to universal financial inclusion see , we perfExploratory analysis of the full model , Model 5While the prevalence of both financial inclusion and recent IPV vary widely across countries, in general, higher levels of women’s financial inclusion were associated with lower levels of recent IPV, even after accounting for asset-based enablers of economic autonomy and gender norms. In the context of rising women's financial inclusion (from 47% worldwide in 2011 to 65% in 2017 ), this iIn models restricted to low and middle income countries, the relationship between levels of women’s financial inclusion and recent IPV, adjusting for the gender gap in financial inclusion, was similar to that seen in the global sample. However this association became non-significant when additional controls were introduced for asset-based enablers of economic autonomy, gender norms and national context, suggesting that at present, these contextual factors explain much of the relationship originally seen between financial inclusion and recent IPV in low and middle income countries. The association between HDI and recent IPV was lost upon accounting for cash earnings and gender norms such as controlling behavior and justification of wife-beating, which is in line with previous research, and emphasizes differences in correlates of IPV across contexts .One interesting and cautionary result is the reversal of the relationship between women’s financial inclusion and recent IPV within low and middle income countries in models that included additional measures of asset-based enablers of economic autonomy and gender norms. Upon adjusting for cash earnings, decision-making over earnings, controlling behavior, and the justification of wife-beating, low and middle income countries with higher levels of financial inclusion tended to have higher levels of IPV. The significance of this result, however, was conditioned on levels of controlling behavior; the positive association between increased women’s financial inclusion and increased recent IPV was only significant in countries where more than 70% of women reported that their spouses exhibited at least one controlling behavior. These countries with higher levels of controlling behavior also tended to be contexts with higher levels of justification of wife beating and higher levels of women’s employment, but also lower levels of cash earnings and more inequitable employment norms . These aThe issue of male control is also of relevance when considering the measurement of women’s financial inclusion. The measure used in this study assesses account ownership  or mobile money service use within the past year among women and girls aged 15 or older; this is a gender-specific version of the indicator used to track progress on Sustainable Development Goal 8.10.2 . The phrWhile fragile state status was associated with increased risk of recent IPV in bivariate analyses, it did not emerge as significant in multivariate analyses. There are several possible explanations for this. The prevalence of recent IPV in fragile states had much wider variability than was seen in non-fragile states . There was only modest variability in financial inclusion in fragile states (ranging only from 3%-33%).This contrast is clear in Afghanistan, which has the highest level of recent IPV (46%) seen across assessed countries, and one of the lowest levels of women’s financial inclusion (4%), vs. Chad, which has 18% recent IPV and 8% women’s financial inclusion. This relationship may have been further compromised in multivariate models by the fact that only 16 of 112 countries were considered fragile states, and sample size was thus limited for this measure. Finally, while previous research has indicated that the normalization of violence in society more broadly may be associated with higher levels of violence against women in the home , fragileThese findings help dissect the complex relationship between financial inclusion and recent IPV, though further research is needed for a full understanding of mechanisms, particularly given the contextual and normative factors on which these the relationship is conditioned , 52. ForOf course these findings must be interpreted in light of limitations inherent in any cross-sectional, ecological analysis, namely that causality cannot be inferred, and that results do not necessarily translate to the community or individual level. Data were collected in different years, though the year of IPV data collection was accounted for in current analyses. We were limited to measures that are publicly available, which do not fully assess all aspects of asset-based enablers of economic autonomy, gender norms or national context, and exclude, for example, measures of independent mobility. Nevertheless, these findings are suggestive and lend important insights that help to unpack the complex relationship between women’s financial inclusion and IPV.Both preventing IPV and expanding financial inclusion have attained major prominence on the global development agenda. Encouragingly, our ecological results suggest that financial inclusion may be an important lever in reducing women’s risk of IPV, but both IPV and financial inclusion exist in the context of social, cultural and normative barriers and enablers. These barriers and enablers influence underlying mechanisms, as well as the country-level manifestations of these relationships. This means that we should not assume that financial inclusion is a universally positive component of development. Our findings underline the importance of shifting underlying norms and controlling behaviors which heighten the risk of violence, and suggest that efforts to promote women’s empowerment may be undermined in the absence of those changes. We add to the body of research suggesting that financial inclusion merits focus within the context of broader efforts to improve the status of women and reduce gender inequitable norms, and that this may offer opportunities to reduce women’s risk of violence at the hands of their partners.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


The cingulum, a major structure in the limbic system, contains the medial cholinergic pathway, which originates from the basalis nucleus of Meynert (Ch 4) in the basal forebrain. The cingulum is involved in various cognitive functions, including memory, attention, learning, motivation, emotion, and pain perception. In this mini-review, 10 studies reporting on recovery mechanisms of injured cinguli in patients with brain injury were reviewed. The recovery mechanisms of the injured anterior cinguli reported in those 10 studies are classified as follows: Mechanism 1, recovery via the normal pathway of the cingulum between the injured cingulum and Ch 4; mechanism 2, recovery through the neural tract between the injured cingulum and the brainstem cholinergic nuclei; mechanism 3, recovery via the lateral cholinergic pathway between the injured cingulum and the white matter of the temporo-occipital lobes; mechanism 4, recovery through the neural tract between the contralesional basal forebrain and the ipsilesional basal forebrain via the genu of the corpus callosum; and mechanism 5, recovery through the neural tract between the injured cingulum and Ch 4 via an aberrant pathway. Elucidation of the recovery mechanisms of injured anterior cinguli might be useful for neurorehabilitation of patients with anterior cingulum injuries. Diffusion tensor tractography appears to be useful in the detection of recovery mechanisms of injured anterior cinguli in patients with brain injury. However, studies on cingulum injury recovery mechanisms are still in the early stages because most of the above studies are case reports confined to a few brain pathologies. Therefore, further studies involving large numbers of subjects with various brain pathologies should be encouraged. In addition, studies on the influencing factors and clinical outcomes associated with each recovery mechanism are warranted. There are several cholinergic nuclei in the human brain –4. Four The cholinergic system of the cerebral cortex is innervated by the medial and lateral cholinergic pathways which mainly originate from Ch 4 . After oElucidation of recovery mechanisms following brain injury is important in neurorehabilitation because such information provides a scientific basis for developing neurorehabilitation strategies and predicting prognosis. The recovery mechanisms of the injured brain are based on the following classical concepts for brain plasticity: (1) unmasking of reserve axons and synapses for particular functions following injury of the ordinarily dominant system, and (2) collateral sprouting from an intact neuron to a denervated region –15. ReceResearch on the recovery mechanisms of injured cinguli has been limited because identification of the cingulum by using conventional brain magnetic resonance imaging has been impossible because it cannot discern the cingulum from other adjacent structures . HoweverIn this mini-review, DTT studies reporting on injured cingulum recovery mechanisms in patients with brain injury are reviewed. Relevant studies in the period 1990 to 2018 were identified by searching within the PubMed, Google Scholar, and MEDLINE electronic databases. The following keywords/abbreviations were used: DTI, DTT, cingulum, anterior cingulum, memory, traumatic brain injury (TBI), stroke, intracerebral hemorrhage (ICH), cerebral infarct, hypoxic-ischemic brain injury (HI-BI), brain tumor, brain injury, brain plasticity, and recovery mechanism. This review was limited to studies of humans with brain injury. We selected the relevant studies according to the flow diagram presented in Figure The recovery mechanisms of the injured anterior cinguli reported in the ten reviewed studies are classified as follows: Mechanism 1, recovery via the normal pathway of the cingulum between an injured cingulum and Ch 4; mechanism 2, recovery through the neural tract between the injured cingulum and the brainstem cholinergic nuclei; mechanism 3, recovery through the lateral cholinergic pathway between the injured cingulum and the white matter of the temporo-occipital lobes; mechanism 4, recovery through the neural tract between the contralesional basal forebrain and the ipsilesional basal forebrain via the genu of the corpus callosum; and mechanism 5, recovery through the neural tract between the injured cingulum and Ch 4 via an aberrant pathway Figure , 22–30.In 2013, Jang and Seo reported on neural recovery of an injured cingulum in a patient who had HI-BI and a subarachnoid hemorrhage (SAH) that was observed on follow-up DTT . At 14 mIn 2016, Jang and Kwon reported on changes to the anterior cingulum in a patient who underwent craniectomy and removal of meningioma and had concurrent ICH . The patIn 2018, Jang et al. reported on a patient with mild TBI who, on follow-up DTT, showed recovery of an injured cingulum concurrent with improvement of short-term memory . The patIn 2012, Yeo et al. presented a case report on a patient who had experienced a traffic accident and underwent conservative management for SAH in the right frontal and left Sylvian fissure . The patIn 2014, Seo and Jang reported on a patient who showed unusual neural connections between the anterior portions of injured cinguli and the brainstem cholinergic nuclei following SAH . The patDuring the same year (2014), Yoo et al. investigated the relationship between cognition and the neural connections from injured cinguli to brainstem cholinergic nuclei in patients with TBI . Twenty In 2016, Jang et al. reported on a patient with TBI who showed recovery of an injured cingulum that progressed via the lateral cholinergic pathway . At 4 weIn 2015, Jang et al. reported on changes in DTT results for the cingulum that coincided with changes in cognitive impairment in a patient with TBI . Upon evRecently, Jang et al. reported on a patient who had developed new neural tracts between the injured anterior cinguli and the basal forebrain following ICH, intraventricular hemorrhage, and SAH after the rupture of an aneurysm in the left middle cerebral artery . When beIn 2016, Jang et al. reported on a patient who, following TBI, appeared to show recovery of an injured anterior cingulum via an aberrant neural tract between an injured cingulum and Ch 4 . The patIn this mini-review article, 10 studies  reporting recovery mechanisms of injured cinguli in patients with brain injuries were reviewed , 22–30. Based on the observations in the reviewed papers, it appears that injured cingulum recovery mechanisms are based on reorganization of the cholinergic innervation between the injured cingulum and the cholinergic nuclei as a means to obtain cholinergic innervation after the loss of cholinergic innervation between the basal forebrain and the anterior cingulum , 34–36. SHJ: study concept and design, manuscript development, and writing. JPS: study concept and design, acquisition and analysis of data, and manuscript authorization.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In the United States, disparities in the rates of HIV care among youth and young adults result from the intersections of factors that include stigma, substance use, homelessness or marginal housing, institutional neglect, and mental health issues. Novel interventions are needed that are geared to youth and young adults.In this paper, we aim to describe the interventions used by participating sites for Using Social Media initiative, the process for classifying the intervention components, and the methods for conducting a comprehensive evaluation of the interventions.In 2015, the Health Resources and Services Administration (HRSA) HIV/AIDS Bureau, Special Projects of National Significance (SPNS) funded the Evaluation and Technical Assistance Center (ETAC) at the University of California, Los Angeles and 10 demonstration projects at sites across the United States that incorporated innovative approaches using a variety of social media and mobile technology strategies designed specifically for youth and young adults living with HIV. The ETAC developed a typology, or a classification system, that systematically summarizes the principal components of the interventions into broader groups and developed a multisite, mixed-methods approach to evaluate them based on the Department of Health and Human Services HIV health outcomes along the HIV care continuum. The mixed-methods approach is key to remove potential biases in assessing the effectiveness of demonstration projects.This SPNS project was funded in September 2015, and enrollment was completed on May 31, 2018. A total of 984 participants have been enrolled in the multisite evaluation. Data collection will continue until August 2019. However, data analysis is currently underway, and the first results are expected to be submitted for publication in 2019.This HRSA-funded initiative seeks to increase engagement in HIV medical care, improve health outcomes for people living with HIV, and reduce HIV-related health disparities and health inequities that affect HIV-positive youth and young adults.DERR1-10.2196/10681 In the United States, HIV-positive youth and young adults have disproportionately lower rates of HIV care engagement, retention, medication adherence, and viral suppression compared with older HIV-positive populations. Zanoni and Mayer  estimateThe largest percentage of HIV-positive youth and young adults are men who have sex with men (MSM). Among Ryan White HIV/AIDS Program (RWHAP) clients aged 13-30, male-to-male sexual contact was the transmission category for 60% of HIV infections, with African Americans (54%) and Latinos (22%) being the largest racial or ethnic groups affected . The RWHMost interventions that address barriers to HIV care have been developed for adults  and haveSignificant gains can be made to improve the health outcomes of HIV-infected youth and young adults using mobile technology and social media for engagement and retention in HIV medical care. Media and technology that facilitate social interaction  are preferred among young adults, who spend more time with social media and mobile technology than any other activity ,22. The To harness and test the potential of social media in the interest of better HIV care engagement for youth, the Health Resources and Services Administration (HRSA) HIV/AIDS Bureau, Special Projects of National Significance (SPNS) program launched the Using Social Media to Improve Engagement, Retention, and Health Outcomes along the HIV Care Continuum initiative (SMI) in 2015. The 4-year initiative includes ten demonstration projects in HIV care sites (n=5), health departments (n=2), and community-based organizations (n=3) located throughout the United States. An Evaluation and Technical Assistance Center (ETAC) was awarded to the Department of Family Medicine at the University of California, Los Angeles (UCLA) to provide technical assistance to the demonstration projects and to develop and implement a rigorous multisite evaluation. Demonstration projects developed mobile technology and social media interventions for linking, retaining, and supporting HIV-positive, underserved, underinsured, hard-to-reach youth (ages 13-24 years) and young adults (ages 25-34 years) in HIV primary care and supportive services. The overarching goal of this initiative is to create a system change—improvements in policies and procedures using social media and mobile technologies—that results in improved HIV health outcomes for HIV-positive youth and young adults.In this paper, we describe the interventions used by participating sites for this initiative, the process for classifying the intervention components, and the methods for conducting a comprehensive evaluation of the interventions.Through a competitive proposal process, HRSA selected demonstration sites using innovative mobile technology and social media strategies deployed via the internet or mobile apps designed to improve engagement and retention in care, medication adherence, and to help achieve viral load suppression among youth and young adults living with HIV  in conceptualizing the strengths and weaknesses of different methodological approaches . In otheHIV medical eligibility criteria for enrollment in the multisite evaluation is based on the US Department of Health and Human Services (HHS) common core indicators for monitoring HHS-funded HIV care services  and inclAdditional eligibility criteria included (1) being between the ages of 13 and 34 years; (2) meeting at least one of the above medical criteria determined from tests or medical records; (3) providing informed consent (if 18 years or older) or providing informed assent (if 13-17 years) and, if required by state laws and regulations, obtaining consent from a parent or legal guardian; and (4) meeting any demonstration site-specific criteria  as necessary.While each demonstration site’s intervention is unique, there are general commonalities listed in the typology framework . For exaFor outreach and recruitment, almost all (n=9) of the sites use social networking sites or apps and other social media platforms . Of thesThe interventions offer a range of functions, as represented in In order to determine the relative effectiveness of the interventions taking part in this initiative, the ETAC is conducting a rigorous, multisite evaluation of the demonstration sites’ interventions. The evaluation plan assesses the outcomes, processes, and cost of using social media- and technology-based interventions to ensure that they have maximum impact on engagement, retention, adherence, and health outcomes of HIV-infected youth and young adults. The design of the quantitative multisite evaluation is informed by the components of each site’s interventions and the type of data the components capture  as well as engagement and outcomes of care measures approved by HHS for funded HIV care services . The demACASI surveys are conducted at baseline enrollment and repeated at 6-, 12-, and 18-month intervals. The five primary domains of the ACASI surveys are: (1) sociodemographic characteristics ; (2) biomedical health, linkage, engagement, and retention in care; (3) intervention exposure; (4) barriers to care; and (5) media technology usage and attitudes. In addition, the surveys collect information on the popularity, adoption, and usability of social media-based interventions among participants. Surveys also gather information on the broader barriers and facilitators of engagement and retention in medical care.Cost assessments are being conducted annually to determine the cost of implementing each intervention. Sites use standard microcosting techniques  combined with direct costs to obtain an estimate of total incremental recurring costs. Development and ongoing maintenance costs of the studies are collected through a cost assessment tool that captures personnel information, recurring goods and services, capital equipment, and facility costs. The costs of developing new mobile apps are captured in the recurring costs reported by the five sites developing them. Cost assessments also indicate successful strategies for labor and programmatic costs for each intervention in this SPNS initiative to inform future replication.Intervention exposure collected weekly helps identify which components of the interventions contribute to desired outcomes. There are two forms of exposure data being captured in the SMI: person-to-person and back-end data. Person-to-person exposure is defined as any type of contact between participants and intervention staff in person, by phone, by text, or by other mobile messaging services. Back-end data include participants’ activities on mobile apps, private Facebook pages, or other social media platforms used in this intervention. Back-end data will be used to measure intervention exposure in the multisite evaluation. Some sites have used real-time measures of back-end data to adjust their intervention. For example, one demonstration intervention removed the gamification component of their mobile app due to lack of use.Data about participants’ HIV health outcomes  are collected every 6 months to assess changes in health outcomes over time. Sites use either the administrative data associated with the receipt of RWHAP funds or abstracted data collected from medical records by hand. Participants’ identification is coded to protect their identities before sites submit data to the ETAC. Information from medical data includes: core service visits for HIV care, substance abuse, mental health, CD4 cell count testing, viral load testing, the first date of antiretroviral prescription, and any breaks in the use of highly active antiretroviral therapy.. In addition, qualitative methods afford a better understanding of participants’ experiences with social media and mobile technology to link, engage, and keep them in HIV medical care. It also provides a means to capture any unanticipated themes that may emerge from the data regarding intervention implementation and acceptability.Qualitative analysis will document the effective implementation of these interventions. Data is being collected by ETAC investigators during years three and four of the initiative through key informant interviews with participants and providers and tracking reports and forms kept by demonstration sites. Qualitative research methodologies are valuable for understanding factors that facilitate or inhibit the implementation and the effectiveness of the intervention, thus providing context and informing quantitative HIV health outcome data The multisite evaluation is assessing engagement in care, health outcomes associated with participation in the social media and mobile technology-based interventions, and individual-level factors that influence the effectiveness of these interventions.The quantitative evaluation primarily looks at associations between intervention type and exposure and changes in HIV care continuum outcomes and related health outcomes over time. Statistically significant changes in outcomes over time will be indicative of a possible intervention effect; we are cautious against using more causal language in the absence of a control group. We will conduct subgroup analyses for data from each of the ten demonstration sites as well as in aggregate to evaluate differential intervention effects across sites. Random effects will be included for each study participant to account for correlations between outcome observations on the same study participant and properly adjust SEs that will be estimated by the regression models. Most of the analyses will be conducted on nonnormally distributed outcomes and will use random effects generalized linear models with appropriate outcome link functions.The qualitative evaluation will document the barriers and facilitators to the effective implementation of interventions. Qualitative data sources include individual, semistructured interviews with participants or clients and key informants , review of secondary sources of information  and site presentations at grantee meetings, and observations of project operations at intervention sites. Interview transcripts will be iteratively coded, sorted, and analyzed using a thematic analysis process . Themes This mixed-methods approach will be important in removing potential bias in establishing the effectiveness of demonstration projects. The findings from the evaluation will provide insight for the future use of social media and mobile technology to improve health outcomes for HIV-positive youth and young adults. The results will include best practices from the demonstration sites, lessons learned, and implications for system change or system integration of social media and mobile technology.Privacy, confidentiality, and security are paramount in designing an intervention that uses social media or mobile technology for engaging and retaining HIV-infected persons in medical care. In addition to firewalls and information technology security procedures required by the Health Insurance Portability and Accountability Act (HIPAA) regulations, unintentional disclosures can result in stigma, discrimination, and prejudice, particularly for HIV-positive patients. Participants in the SMI are trained in device security, such as using passwords to access phones, added layers of password protection to access specific apps, how to clear text message logs, etc, by SPNS staff at the demonstration sites. Awareness of current privacy concerns associated with each technology has helped alleviate participant concerns. HIPAA requirements must be adhered to when using mobile technologies and social media connected to patients’ personal health information.This SPNS project was funded in September 2015, and enrollment was completed on May 31, 2018. A total of 984 participants have been enrolled in the multisite evaluation. Data collection will continue until August 2019. However, data analysis is currently underway, and the first results are expected to be submitted for publication in 2019.The Social Media Initiative is an HRSA SPNS initiative that emphasizes the primary goals for HIV prevention and care outlined in the US National HIV/AIDS Strategy: to reduce new infections, increase access to care, improve health outcomes for people living with HIV, and reduce HIV-related health disparities and health inequities that HIV-positive youth and young adults face. The innovative interventions included in this initiative have the potential to improve the health outcomes of youth and young adults who are living with HIV.The ETAC at UCLA aims to complete the analysis and dissemination of findings, best practices, and lessons learned from using social media and mobile technology to support the engagement of HIV-positive youth and young adults in medical care by the end of 2019. The ETAC hopes that the findings will serve to inform future policy and practices for programs seeking to use ever-changing and improving social media platforms and mobile technology in the delivery of high quality, culturally appropriate HIV primary health care interventions. Successful scale-up of these types of interventions will require understanding how and why youth and young adults use social media and emerging mobile technologies for personal health.


Meeting the growing demand for food in the future will require adaptation of water and land management to future conditions. We studied the extent of different adaptation options to future global change in the Mediterranean region, under scenarios of water use and availability. We focused on the most significant adaptation options for semiarid regions: implementing irrigation, changes to cropland intensity, and diversification of cropland activities. We used Conversion of Land Use on Mondial Scale (CLUMondo), a global land system model, to simulate future change to land use and land cover, and land management. To take into account future global change, we followed global outlooks for future population and climate change, and crop and livestock demand. The results indicate that the level of irrigation efficiency improvement is an important determinant of potential changes in the intensity of rain-fed land systems. No or low irrigation efficiency improvements lead to a reduction in irrigated areas, accompanied with intensification and expansion of rain-fed cropping systems. When reducing water withdrawal, total crop production in intensive rain-fed systems would need to increase significantly: by 130% without improving the irrigation efficiency in irrigated systems and by 53% under conditions of the highest possible efficiency improvement. In all scenarios, traditional Mediterranean multifunctional land systems continue to play a significant role in food production, especially in hosting livestock. Our results indicate that significant improvements to irrigation efficiency with simultaneous increase in cropland productivity are needed to satisfy future demands for food in the region. The approach can be transferred to other similar regions with strong resource limitations in terms of land and water.The online version of this article (10.1007/s11027-017-9761-0) contains supplementary material, which is available to authorized users. Irrigated cropland has a significant share in the global crop production and allows human presence and a stable crop production in areas otherwise inhabitable  is a spatial land system change model, where future changes to the landscape are driven by multiple demands , such asCLUMondo allocates changes to land systems based on local spatial preference, area restrictions, and competition between land systems  and pine (Pinus sp.) forests, and although they are used to the semiarid Mediterranean climate, they mostly occur in hilly and mountainous areas with sufficient rainfall , forced by the Representative Concentration Pathway 4.5 (RCP4.5) greenhouse gas radiative forcing , barley (Hordeum vulgare), maize (Zea mays), and rice (Oryza sativa), together with vegetables including tomatoes (Solanum lycopersicum) and potatoes (Solanum tuberosum). Permanent crops contain fruit such as apples , pears (Pyrus sp.), peaches (Prunus persica), grapes (Vitis vinifera), citrus (Citrus sp.), olives (Olea europaea), and dates (Phoenix dactylifera). Livestock numbers consist only of ruminant species: cattle (Bos taurus), goats (Capra aegagrus), and sheep (Ovis aries). The production of annual and permanent crops is based on food production projections in the SSP2 Marker scenario and livestock production on projected livestock numbers . Dehesas/montados are primarily used for grazing of cattle (Bos taurus), sheep (Ovis aries), goats (Capra aegagrus), and also pigs (Sus scrofa domesticus). They provide valuable non-timber forest products such as cork, firewood, and acorns. In the understory layer, cereals such as wheat (Triticum aestivum), oats (Avena sativa). or barley (Hordeum vulgare) are often cultivated. Grazing, cereal cultivation, and forestry therefore occur at the same time in these landscapes . Although a reduction in irrigated areas seems unrealistic, it is occurring on a local scale. Crops with significant water needs such as citruses are being substituted with crops with lower or no irrigation demands arid region are projected to experience significant increases in food demand, and analyzing future change to land management in these regions should consider potential changes to water resources. We have also shown how future land system change is influence by the level of technological improvement, resulting in improved irrigation efficiency or cropland productivity. When developing scenarios with plausible technological improvements, we suggest focusing on regionally significant adaptation options. Finally, this study presents a relatively straightforward approach that can also be used in other regions, as it is mostly based on publicly accessible spatial data and statistics. Combining data on land use, management intensity, and irrigation, with crop production and water withdrawal values, however, demands a certain level of generalization, depending on the spatial scale.Meeting the future demands for agricultural production and the challenges of climate change requires more than efficient irrigation: also within the other land systems, changes in intensity and crop type will be needed. This study indicates that the extent of simulated adaptation in land management heavily depends on the level of water used efficiently. In practice, the potential of a region to produce crops that need irrigation is limited with the region’s ability to invest in irrigation. The Mediterranean south has a considerably higher share of irrigation with highest water losses Table  Jägerme. These sWe did not consider the depletion of freshwater resources due to unsustainable water extraction use and climate change, already occurring in the region