CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

Factors influencing participation in physical activity for persons living with dementia in rural and northern communities in Canada: a qualitative study.

OBJECTIVE: In recognition that engagement in physical activities for persons living with dementia can be challenging in rural and northern communities, the objective of this study was to explore the factors influencing physical activity participation among persons living with dementia in rural/northern communities and to identify the locally-driven mitigation strategies participants used to address barriers to physical activity. SETTING: Interviews and focus groups were conducted in two locations in northern British Columbia, Canada including a rural community (<10 000 persons) and a medium-sized geographically isolated city (<80 000 persons). Both communities are located at substantial distances (>700 km) from larger urban centres. PARTICIPANTS: Twenty-nine individuals participated including healthcare providers (n=8), community exercise professionals (n=12), persons living with dementia (n=4) and care partners (n=5). RESULTS: Rural and northern contextual factors including aspects of the built and natural environment were the main drivers of physical activity for persons living with dementia. Limited capacity in the health system to support physical activity due to a lack of referrals, poor communication mechanisms and limited resources for programming created challenges for physical activity participation. At the community level, local champions filled gaps in physical activity programming by leveraging informal networks to organise opportunities. Programme-level factors included a lack of consistency in staff, and challenges defining programme scope given limited population size and the fear of stigma for persons living with dementia. CONCLUSIONS: Environmental context and limited access to specialised programming affect the opportunities for persons living with dementia to engage in physical activities. Rural and northern communities showed resiliency in providing physical activity opportunities yet remained fragile due to human resource challenges. Without reliable resources and sustained support from the health system, local champions remain vulnerable to burnout. Enhancing support for local champions may provide greater stability and support to physical activity promotion in rural and northern communities.

Policy and practice of checking vaccination status at school in 2018, a global overview.

BACKGROUND: Checking vaccination status at school is widely recommended as a strategy to strengthen routine childhood vaccination coverage. Documentation of approaches, challenges, strengths, and impact of this strategy in a variety of contexts is key to enhancing adoption and implementation. However, there is limited information about the prevalence of policies and the implementation of checking vaccination status at school globally. METHODS: A one-time supplementary survey was circulated with the annual World Health Organization (WHO) and United Nations International Children's Emergency Fund (UNICEF) Joint Reporting Form in 2019 to all WHO member states and non-member state reporting entities. Additional publicly available country-level data, including primary school enrollment, home-based record (HBR) ownership, and World Bank income classification were linked to the supplementary survey responses, which were descriptively analyzed. RESULTS: We received survey responses from 130 of the 194 (67%) WHO member states and 15 non-member state reporting entities. Almost half (46%) of the respondents reported having a law requiring proof of vaccination to enter at least one level of education, and 60% of the respondents reported having a law that requires checking vaccination status at school in 2018. Three-quarters of the respondents (77%) reported the practice of routinely checking vaccination status at school. Both laws and the practice of checking were more common in the WHO Region of the Americas and the WHO European Region, and in high- and upper-middle-income countries. Individual HBR was the document most frequently checked. Catch-up vaccination occurred most frequently at health centers. Evaluation of checking vaccination status at school to determine what has worked and its effect was infrequently reported. CONCLUSION: Despite widespread implementation of checking vaccination status at school in 2018, documentation of the experiences in planning and implementing this strategy, and its effects remains sparse, particularly in low- and middle-income countries.

An assessment of the contribution of National Stop Transmission of Polio Program to Nigeria's Immunization Program.

Introduction: In July 2012, the National Stop Transmission of Polio (NSTOP) program was established to support the Government of Nigeria in interrupting transmission of poliovirus and strengthen routine immunization (RI). NSTOP has approximately 300 staff members with the majority based at the Local Government Area (LGA) level in northern Nigeria. Methods: An internal assessment of NSTOP was conducted from November 2015 to February 2016 to document the program´s contribution to Nigeria´s immunization program and plan future NSTOP engagement. A mixed methods design was used, with data gathered from health facility, LGA, state, and national levels, through structured surveys, interviews, focus group discussions, and review of program records. Survey and expenditure data were summarized by frequency and trends over time, while interview and focus group data were analyzed qualitatively for key themes. Results: The majority of the 111 non-NSTOP LGA respondents reported that NSTOP officers supported polio campaigns (100%) and supervised RI sessions (99.1%). Out of 181 respondents at health facility level, the majority reported that NSTOP trainings improved their knowledge (83.3%) and skills (76.2%) on RI, and NSTOP officers regularly supervised their RI sessions (96.7%). Most respondents reported that there would be a negative impact on immunization activities if NSTOP officers were withdrawn. Conclusion: Future implementation of NSTOP should be realigned to (a) give highest priority to mentoring LGA staff to build institutional capacity, (b) ensure increased capacity translates to improved provision of RI services, and (c) improve routine review of program monitoring data to assess progress in both polio and RI programs.

Implementation of Physical Activity Interventions in Rural, Remote, and Northern Communities: A Scoping Review.

Compared with urban centers, rural, remote, and northern communities face substantial health inequities and increased rates of noncommunicable disease fuelled, in part, by decreased participation in physical activity. Understanding how the unique sociocultural and environmental factors in rural, remote, and northern communities contribute to implementation of physical activity interventions can help guide health promotion policy and practice. A scoping review was conducted to map literature describing the implementation of physical activity interventions in rural, remote, and/or northern communities. Databases MEDLINE, PsycINFO, EMBASE, CINAHL, and SPORTDiscus were searched using a predetermined search strategy. Outcomes of interest included community demographics, program characteristics, intervention results, measures of implementation, and facilitators or barriers to implementation. A total of 1672 articles were identified from a search of databases, and 8 from a targeted hand search. After screening based on inclusion and exclusion criteria, 12 articles were summarized in a narrative review. Prominent barriers to physical activity program implementation included transportation, lack of infrastructure, sociocultural factors, and weather. Facilitators of program success included flexibility and creativity on the part of the implementation team, leveraging community relationships, and shared resources. Few papers reported on traditional implementation outcomes such as fidelity, dose, and quality. There is a lack of rigorous implementation evaluations of physical activity interventions delivered in rural, remote, or northern communities. Positive aspects of rural life, such as social cohesion and willingness to share resources, appear to contribute to successful program implementation.

"Not Everybody's an Athlete, But They Certainly Can Move": Facilitators of Physical Activity Maintenance in Older Adults in a Northern and Rural Setting.

Although the benefits of maintaining a physical activity regime for older adults are well known, it is unclear how programs and facilities can best support long-term participation. The purpose of this study is to determine the facilitating factors of physical activity maintenance in older adults at individual, program, and community levels. Nine semistructured interviews were conducted with individuals aged 60 years and older and long-term participants (>6 months) in community-based group exercise at a clinical wellness facility in northern British Columbia, Canada. Interviews were audio recorded, transcribed, and analyzed via inductive thematic analysis. Themes identified as facilitators of physical activity included (a) social connections, (b) individual contextual factors, and (c) healthy aging. Older adults are more likely to maintain physical activity when environments foster healthy aging and provide opportunity for social engagement.

Exploring the perspectives of community members as research partners in rural and remote areas.

BACKGROUND: Community engagement in research has the potential to support the development of meaningful health promotion interventions to address health inequities. People living in rural and remote areas face increased barriers to participation in health research and may be unjustly excluded from participation. It is necessary to understand the process of patient and public engagement from the perspective of community members to support partnered research in underserved areas. The aim of this project was to increase understanding on how to include community members from rural and remote areas as partners on research teams. METHODS: Using purposive sampling, we completed semi-structured interviews with a representative sample of 12 community members in rural and remote areas of northern British Columbia, Canada. Interviews were audio recorded and transcribed verbatim. Following an integrated knowledge translation approach, an inductive thematic analysis was completed to incorporate researcher and knowledge user perspectives. RESULTS: The factors important to community members for becoming involved in research include: 1) relevance; 2) communication; and 3) empowering participation. The analysis suggests projects must be relevant to both communities and individuals. Most participants stated that they would not be interested in becoming partners on research projects that did not have a direct benefit or value for their communities. Participants expressed the need for clear expectations and clarification of preferred communication mechanisms. Communication must be regular, appropriate in length and content, and written in a language that is accessible. It is essential to ensure that community members are recognized as subject matter experts, to provide appropriate training on the research process, and to use research outcomes to support decision making. CONCLUSIONS: To engage research partners in rural and remote communities, research questions and outcomes should be co-produced with community members. In-person relationships can help establish trust and bidirectional communication mechanisms are prudent throughout the research process, including the appropriate sharing of research findings. Although this project did not include community members as research team members or in the co-production of this research article, we present guidelines for research teams interested in adding a patient or public perspective to their integrated knowledge translation teams.

School-based delivery of routinely recommended vaccines and opportunities to check vaccination status at school, a global summary, 2008-2017.

School-based vaccination (SBV) and checking students' vaccination records at school have the potential to optimize vaccination coverage among school-aged children. The primary aim of this paper is to describe adoption of SBV by countries from 2008 to 2017, including target age groups and vaccines delivered in 2017, as reported annually through the World Health Organization (WHO)-United Nations Children's fund (UNICEF) Joint Reporting Form (JRF). Expanding upon previous analyses, country-specific rates of primary school enrollment and home-based record (HBR) ownership were linked to the WHO-UNICEF JRF data, to identify countries with high potential to implement vaccination record checks at school. The proportion of countries reporting delivery of at least one routinely recommended vaccine dose in school settings increased from 95 (of 163 reporting; 58%) in 2008 to 108 (of 181 reporting; 60%) in 2017. The 13 additional countries that reported using SBV in 2017 were among 31 countries for which SBV data from the JRF were unavailable in 2017. The most common antigens delivered through SBV in 2017 were tetanus (94 countries), diphtheria (89 countries), and human papillomavirus (52 countries). Among 93 countries with data available for net primary school enrollment and HBR ownership, 52 (56%) countries had both ≥80% net primary school enrollment and ≥80% of children aged 12-23 months ever owning an HBR; 33 (63%) of these used SBV. If not already doing so, these 33 countries represent an opportunity to introduce routine checking of vaccination status at entry to, or during primary school. With the growing number of new vaccines and booster doses of childhood vaccines targeting school-age children, implementation of SBV and checking of student vaccination records at school may help improve vaccination coverage; however, additional data are needed to assess global prevalence of checking vaccination status at school and to identify factors facilitating optimal implementation of this strategy.

Financial cost analysis of a strategy to improve the quality of administrative vaccination data in Uganda.

BACKGROUND: High-quality vaccination data are critical to planning, implementation and evaluation of immunization programs. However, sub-optimal administrative vaccination data quality in low- and middle-income countries persist for heterogeneous reasons, though most relate to organizational factors and human behavior. The nationwide Data Improvement Team (DIT) strategy in Uganda aimed to strengthen human resource capacity to generate quality administrative vaccination data at the health facility. METHODS: A financial cost analysis of the Uganda DIT strategy (2014-2016) was conducted from the program funder perspective. Activity-based micro-costing from funder financial and program monitoring records was used to estimate total and unit costs by program area (in 2016 US dollars). Hypothetical scenarios were developed to illustrate potential approaches to reducing costs. RESULTS: Over 25 months the DIT strategy was implemented in all 116 operational districts and 3443 (89%) health facilities in Uganda at a total financial cost of US $575 275. Training and deployment of DITs accounted for the highest proportion of expenditure across program areas (69%). Transport, per diems, lodging, and honoraria for DIT members and national supervisors were the main cost drivers of the strategy. Deployment of 557 DIT members cost US $839 per DIT member, US $4 030 per district, and US $136 per health facility. The estimated opportunity cost of government staff time wasn't a major cost driver (2.5%) of total cost. CONCLUSION: The results provide the first estimates of the magnitude and drivers of cost to implement a national workforce capacity building strategy to improve administrative vaccination data quality in a low- or middle-income country. Financial costs are a critical input to combine with future outcome data to describe the cost of strategies relative to performance outcomes. The operational costs of the strategy were modest (0.5-1.6%) relative to the estimated operational costs of Uganda's national immunization program.

Move the north: evaluation of a regional stakeholder engagement initiative to support the development of a community-partnered physical activity research agenda.

BACKGROUND: Although it is generally accepted that engaging with members of the public contributes to more actionable and relevant research, there are a limited number of reported evaluations of community engagement initiatives. Certain populations, such as those with lower socioeconomic status and those who live in rural or dispersed communities, tend to face increased barriers to engagement. For researchers and community members alike, it is important to understand and evaluate engagement initiatives to support participatory research methods, particularly when working with underserved or hard to reach populations. METHODS: Over 2-days in October 2018, we hosted a Research Agenda Development Workshop and Physical Activity Summit with relevant researchers, health professionals, and community partners. The objectives of this initiative were to develop a physical activity research agenda based on community-identified priorities, create networking opportunities, and understand factors impacting physical activity participation in communities across northern British Columbia (BC). An evaluation plan was created early in the planning process to understand the reach of the event based on representation targets. Stakeholder satisfaction with the event was evaluated with a post-meeting survey. RESULTS: The event was successful in engaging community members from a broad geographic region with at least 90 people in attendance from 11 different northern BC communities, representing 46 different organizations. Meeting attendees indicated they were satisfied with the event and felt their perspectives were heard. To advance physical activity in the region, the most commonly desired outcome from the event was the need for ongoing communication channels to support knowledge translation and capacity building in the low-resourced communities of northern BC. There were some gaps in representation targets present at the event. Namely, there were a limited number of people representing Indigenous organizations, and the education and private sectors. CONCLUSIONS: This two-day event was successful at achieving its objectives and engaged a diverse group of stakeholders from a broad geographic region. The outcomes from this event are being used to develop a community-partnered physical activity research agenda and contribute to ongoing learning by the research team to understand contextual factors influencing physical activity in the communities of northern BC. This model of engagement could be used by other researchers interested in engaging with a diverse, multi-sector group of academics, health professionals and community members to support community-centered population health research.

Building health workforce capacity for planning and monitoring through the Strengthening Technical Assistance for routine immunization training (START) approach in Uganda.

INTRODUCTION: The Global Vaccine Action Plan identifies workforce capacity building as a key strategy to achieve strong immunization programs. The Strengthening Technical Assistance for Routine Immunization Training (START) approach aimed to utilize practical training methods to build capacity of district and health center staff to implement routine immunization (RI) planning and monitoring activities, as well as build supportive supervision skills of district staff. METHODS: First implemented in Uganda, the START approach was executed by trained external consultants who used existing tools, resources, and experiences to mentor district-level counterparts and, with them, conducted on-the-job training and mentorship of health center staff over several site visits. Implementation was routinely monitored using daily activity reports, pre and post surveys of resources and systems at districts and health centers and interviews with START consultants. RESULTS: From July 2013 through December 2014 three START teams of four consultants per team, worked 6 months each across 50 districts in Uganda including the five divisions of Kampala district (45% of all districts). They conducted on-the-job training in 444 selected under-performing health centers, with a median of two visits to each (range 1-7, IQR: 1-3). More than half of these visits were conducted in collaboration with the district immunization officer, providing the opportunity for mentorship of district immunization officers. Changes in staff motivation and awareness of challenges; availability and completion of RI planning and monitoring tools and systems were observed. However, the START consultants felt that potential durability of these changes may be limited by contextual factors, including external accountability, availability of resources, and individual staff attitude. CONCLUSIONS: Mentoring and on-the-job training offer promising alternatives to traditional classroom training and audit-focused supervision for building health workforce capacity. Further evidence regarding comparative effectiveness of these strategies and durability of observed positive change is needed.

Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health.

BACKGROUND: Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear. METHODS: We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat. RESULTS: We identified 42 smoking-methylation and 42 smoking-expression signals, where five genes (AHRR, CYP1A1, CYP1B1, CYTL1, F2RL3) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1, and at tissue-shared smoking signals, such as NOTCH1. At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation. CONCLUSIONS: Our results provide the first comprehensive characterization of coordinated DNA methylation and gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung.

Definitive Zygosity Scores in the Peas in the Pod Questionnaire is a Sensitive and Accurate Assessment of the Zygosity of Adult Twins.

Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the 'peas in the pod' questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.

Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci.

Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed epigenome. Furthermore, large genetic variants alter epigenetic signal dosage. Here, we identify DNA methylation variability between GWAS-SNP risk and non-risk haplotypes. In three subsets comprising 3128 MeDIP-seq peripheral-blood DNA methylomes, we find 7173 consistent and functionally enriched Differentially Methylated Regions. 36.8% can be attributed to common non-SNP genetic variants. CpG-SNPs, as well as facilitative TFBS-motifs, are also enriched. Highlighting their functional potential, CpG-SNPs strongly associate with allele-specific DNase-I hypersensitivity sites. Our results demonstrate strong DNA methylation allelic differences driven by obligatory or facilitative genetic effects, with potential direct or regional disease-related repercussions. These allelic variations require disentangling from pure tissue-specific modifications, may influence array studies, and imply underestimated population variability in current reference epigenomes.

Enhancing Workforce Capacity to Improve Vaccination Data Quality, Uganda.

In Uganda, vaccine dose administration data are often not available or are of insufficient quality to optimally plan, monitor, and evaluate program performance. A collaboration of partners aimed to address these key issues by deploying data improvement teams (DITs) to improve data collection, management, analysis, and use in district health offices and health facilities. During November 2014-September 2016, DITs visited all districts and 89% of health facilities in Uganda. DITs identified gaps in awareness and processes, assessed accuracy of data, and provided on-the-job training to strengthen systems and improve healthcare workers' knowledge and skills in data quality. Inaccurate data were observed primarily at the health facility level. Improvements in data management and collection practices were observed, although routine follow-up and accountability will be needed to sustain change. The DIT strategy offers a useful approach to enhancing the quality of health data.

Epigenetic discrimination of identical twins from blood under the forensic scenario.

Monozygotic (MZ) twins share the same STR profile, demonstrating a practical problem in forensic casework. DNA methylation has provided a suitable resource for MZ twin differentiation; however, studies addressing the forensic feasibility are lacking. Here, we investigated epigenetic MZ twin differentiation from blood under the forensic scenario comprising i) the discovery of candidate markers in reference-type blood DNA via genome-wide analysis, ii) the technical validation of candidate markers in reference-type blood DNA using a suitable targeted method, and iii) the analysis of the validated markers in trace-type DNA. Genome-wide methylation analysis in blood DNA from 10 MZ twin pairs resulted in 19-111 twin-differentially methylated sites (tDMSs) per pair with >0.3 twin-to-twin differences. Considering all top three candidate tDMSs across all pairs in the technical validation based on methylation-specific qPCR, 67.85% generated >0.1 twin-to-twin differences. Of the validated tDMSs, 68.4% showed >0.1 twin-to-twin differences with qPCR in trace-type DNA across 8 pairs. Using an updated marker selection strategy, 8 additional candidate tDMSs were obtained for an example MZ pair, of which 7 showed >0.1 twin-to-twin differences in both reference- and trace-type DNA. Lastly, we introduce a high-resolution melting curve analysis of the entire fragment that can complement the proposed approach. Overall, our study demonstrates the general feasibility of epigenetic twin differentiation in the forensic context and highlights that the number of informative tDMSs in the final trace DNA analysis is crucial, as some candidate markers identified in reference DNA were shown not informative in the trace DNA due to various, including technical, reasons. Future studies will need to address the optimal number of epigenetic markers required for reliable identification of MZ twin individuals including statistical considerations.

Lessons Learned and Legacy of the Stop Transmission of Polio Program.

In 1988, the by the World Health Assembly established the Global Polio Eradication Initiative, which consisted of a partnership among the World Health Organization (WHO), Rotary International, the Centers for Disease Control and Prevention (CDC), and the United Nations Children's Fund. By 2016, the annual incidence of polio had decreased by >99.9%, compared with 1988, and at the time of writing, only 3 countries in which wild poliovirus circulation has never been interrupted remain: Afghanistan, Nigeria, and Pakistan. A key strategy for polio eradication has been the development of a skilled and deployable workforce to implement eradication activities across the globe. In 1999, the Stop Transmission of Polio (STOP) program was developed and initiated by the CDC, in collaboration with the WHO, to train and mobilize additional human resources to provide technical assistance to polio-endemic countries. STOP has also informed the development of other public health workforce capacity to support polio eradication efforts, including national STOP programs. In addition, the program has diversified to address measles and rubella elimination, data management and quality, and strengthening routine immunization programs. This article describes the STOP program and how it has contributed to polio eradication by building global public health workforce capacity.

Improving the efficiency and standards of a National Immunization Program Review: lessons learnt from United Republic of Tanzania.

A National Immunization Program Review (NIP Review) is a comprehensive external assessment of the performance of a country's immunization programme. The number of recommended special-topic NIP assessments, such as those for vaccine introduction or vaccine management, has increased. These assessments often have substantial overlap with NIP reviews, raising concern about duplication. Innovative technical and management approaches, including integrating several assessments into one, were applied in the United Republic of Tanzania's 2015 NIP Review. These approaches and processes were documented and a post-Review survey and group discussion. The Tanzania Review found that integrating assessments so they can be conducted at one time was feasible and efficient. There are concrete approaches for successfully managing a Review that can be shared and practiced including having a well-planned desk review and nominating topic-leads. The use of tablets for data entry has the potential to improve Review data quality and timely analysis; however, careful team training is needed. A key area to improve was to better coordinate and link findings from the national-level and field teams.

Shotgun Metagenomics of 250 Adult Twins Reveals Genetic and Environmental Impacts on the Gut Microbiome.

The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing have included only a few samples. Here, we sequenced fecal samples from 250 adult twins in the TwinsUK registry and constructed a comprehensive gut microbial reference gene catalog. We demonstrate heritability of many microbial taxa and functional modules in the gut microbiome, including those associated with diseases. Moreover, we identified 8 million SNPs in the gut microbiome and observe a high similarity in microbiome SNPs between twins that slowly decreases after decades of living apart. The results shed new light on the genetic and environmental influences on the composition and function of the gut microbiome that could relate to risk of complex diseases.

Novel regional age-associated DNA methylation changes within human common disease-associated loci.

BACKGROUND: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. RESULTS: In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19-82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue. This included 52 novel regions, 29 within loci not covered by 450 k or 27 k Illumina array, and with enrichment for DNase-I Hypersensitivity sites across the full range of tissues. These age-associated differentially methylated regions also show marked enrichment for enhancers and poised promoters across multiple cell types. In a replication set of 2084 DNA methylomes, 95.7 % of the age-associated differentially methylated regions showed the same direction of ageing effect, with 80.3 % and 53.5 % replicated to p < 0.05 and p < 1.85 × 10-8, respectively. CONCLUSION: By analysing the functionally enriched disease and trait-associated regions of the human genome, we identify novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases.