Nanotechnology has significant economic, health, and environmental benefits, including renewable energy and innovative environmental solutions. Manufactured nanoparticles have been incorporated into new materials and products because of their novel or enhanced properties. These very same properties also have prompted concerns about the potential environmental and human health hazard and risk posed by the manufactured nanomaterials. Appropriate risk management responses require the development of models capable of predicting the environmental and human health effects of the nanomaterials. Development of predictive models has been hampered by a lack of information concerning the environmental fate, behavior and effects of manufactured nanoparticles. The United Kingdom (UK) Environmental Nanoscience Initiative and the United States (US) Environmental Protection Agency have developed an international research program to enhance the knowledgebase and develop risk-predicting models for manufactured nanoparticles. Here we report selected highlights of the program as it sought to maximize the complementary strengths of the transatlantic scientific communities by funding three integrated US-UK consortia to investigate the transformation of these nanoparticles in terrestrial, aquatic, and atmospheric environment. Research results demonstrate there is a functional relationship between the physicochemical properties of environmentally transformed nanomaterials and their effects and that this relationship is amenable to modeling. In addition, the joint transatlantic program has allowed the leveraging of additional funding, promoting transboundary scientific collaboration. Nanomaterials also offer detection advantages for use in national security emergencies, and innovative approaches to address current environmental concerns  2] 3]. [3].2] [. [3].2] https://clintonwhitehouse4.archives.gov/textonly/WH/EOP/OSTP/html/00_121_3.html). At the foundation of the Initiative was the vision of enabling the control of matter at the nanoscale in order to facilitate a revolution in technology and industry. To materialize this vision, the US Congress enacted the 21st Century Nanotechnology Research and Development Act (P.L. 108–153). The Act provided a statutory foundation for the NNI, established programs, assigned federal agency responsibilities, authorized funding levels, and promoted nanotechnology research to address key issues. To ensure harmonious progress of the Initiative, federal agencies were tasked with developing programs consistent with their mission and authority. Under the NNI guidance, the Office of Research and Development (ORD) in the Environmental Protection Agency (EPA), has initially developed a program of research grants focused on environmental applications of nanotechnology with an emphasis on prevention, detection, and remediation of environmental pollution. As concerns of the unintended consequences of nanotechnology have emerged, the focus of EPA’s nanotechnology grants program shifted to advance the understanding of the environmental implications and risks of nanotechnology.In 2000, the National Nanotechnology Initiative (NNI) was created in the US to ensure the development of nanotechnology . The 2005 UK Government response highlighted the need for a cross-disciplinary approach led by the research community . To address the challenge, in 2006, in the UK a group of funding agencies led by the Natural Environment Research Council (NERC) established the Environmental Nanoscience Initiative (ENI)1, a research program on hazard, exposure and environmental risk posed by manufactured nanomaterials. ENI funded exploratory research projects in 2006 and 2007 aimed at building capacity within the UK scientific community. At the same time, the increasing awareness about the knowledge gaps surrounding environmental implications of nanotechnology was highlighted in a report by the Royal Commission on Environmental Pollution published in 2008 (https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/228871/7468.pdf). Again, the UK Government response agreed with the report’s recommendations as to the need to create an integrated approach to investigate the environmental implications of nanotechnologies with a priority focus on commercially available nanomaterials (https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/228785/7620.pdf). These recommendations strengthen the ENI vision to consider large research projects of transdisciplinary nature joining expertise from across continents.In 2004, the Royal Society and Royal Academy of Engineering in the United Kingdom (UK) published a seminal report highlighting how little it was known about how manufactured nanomaterials enter the environment, how they behave, their fate, and possible effects on plants, animals and humans  has led to concerns about their exposure and hazard  and undehttps://www.epa.gov/research-grants) announced the development of a bilateral nanotechnology research program  with financial support provided jointly by UKENI, USEPA and the US Consumer Product Safety Commission (USCPSC). The program issued a call for proposals and subsequently funded three large, interdisciplinary UK-US consortia; 1) Transatlantic Initiative for the Nanotechnology and the Environment (TINE), 2) Manufactured Nanomaterial Bioavailability & Environmental Exposure (Nano-Bee) and 3) Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC). Each consortium developed an integrated, transatlantic team of scientists, with complimentary expertise to address joint research objectives. The research objectives, specific media, and case studies associated with these consortia are shown in In 2009, The UKENI and USEPA/ORD’s Science to Achieve Results (STAR) grants program (2) and silver (Ag) nanoparticles in realistic environmental conditions by investigating their behavior, bioavailability, trophic transfer, and ecological effects during sewage treatment and following application to agricultural soils. TINE also aimed to determine whether risk assessment models and regulations for land applications of biosolids could be extrapolated to MNMs.The primary route for MNMs  to enter terrestrial ecosystems is by wastewater treatment plants  via the Pilot-scale wastewater treatment plant studies showed that nanomaterials mostly partitioned in the sewage sludge with only a low fraction recovered in the treatment process effluents. Within the treatment plant, Ag and ZnO nanomaterials were completely transformed to a variety of secondary mineral phases. According to X-ray based speciation studies, transformation of bulk  was similar to that of dissolved metals . LaboratMedicago trunculatag rew less, had fewer root nodules, and accumulated more Zn when exposed to aged nanomaterial-treated biosolids compared with the bulk-treated biosolids  [22 [222 [21The research findings have been used to develop a first generation “Life-Cycle-Analysis-inspired Risk Assessment” (LCA-RA) predictive model of nanomaterials fate following transfer from sewage treatment plants to terrestrial environment. The TINE consortium developed a model of Ag and ZnO nanomaterials transport and transformation in agricultural fields and through watersheds  24] [25 [2524] . This reTINE researchers have also developed a new functional assay-based approach for predicting nanomaterial fate and effects  30]. Fo. Fo30]. 2), ZnO, and Au in model aquatic organisms using a wide range of endpoints. Although some work was performed with commercial nanomaterials, a critical output was the generation of a library of nanomaterials with tightly controlled physical and chemical properties, which were characterized using a multi-method approach . Th. Th2), Zapproach  36] to  to 2), Zapproach . Collaboapproach  and exteapproach . PhysicoLymnaea stagnalis, Daphnia magna and Lumbriculus variegatus, with a particular focus on Ag nanoparticles  [41 [41Lymnaarticles . In sevearticles  with bioarticles . In a sisolution . A similsolution  46]. Th. ThLymnasolution  47]..Lymnaea The NanoBee consortium also studied the visualization of nanomaterials including Au, Ag and carbon-based nanomaterials which are difficult to visualize . ResearcNanoparticles toxicity was further studied in a range of aquatic organisms using both targeted toxicological assays and non-targeted (transcriptomic and metabolomics) approaches. At low concentrations, stimulatory effects have been seen in bacteria and hydroponically grown plants and toxicity was observed at higher concentrations  56] [57 [5756]  50]..50].2) incorporated in selected consumer products. The overall hypothesis of the RAMNUC consortium is that the physicochemical and toxicological properties of MNMs at the point of exposure will substantially differ from those at the source . These differences may have significant consequences on MNMs’ bioavailability, induction of oxidative stress, inflammation, and other toxicity measures. Therefore, RAMNUC aimed to understand how these nanoparticles transform as they enter and move through the atmosphere and become inhaled.The RAMNUC consortium conducted research to assess human health risk caused by inhalation exposure to MNMs  suggested an inflammatory response due to either product solvent and/or interaction of the Ag with the solvent. Similar results were reported with nanoparticulate Zn-containing sprays (TheraZinc™ and DermaZinc™). The overall toxicity was dependent on the type of nanoparticle and the solvent. These studies emphasize the importance of testing nanomaterials as they occur in commercial products, as the product solvent may alter the fate, behaviour and toxicity of the nanoparticles, and unintended inhalation could cause adverse health effects  whi whiin vial media  [73]. Moparticles.The US-UK joint program in nanotechnology research has allowed US and UK scientists to collaborate and share knowledge across national borders in an effort to understand the complexities associated with nanomaterial toxicity and environmental behavior. The international collaboration provided a platform for the consortia to take a robust, systematic approach that pooled strengths and expertise across disciplines. These projects have supported transboundary working practices and allowed the leveraging of additional funding promoting effective use of limited research resources. For example, TINE has developed a joint US-European Union collaboration to optimize the use of nanomaterial-containing products for agricultural benefits. The new project, NanoFARM, is expected to play a key role in ensuring the safe development of agricultural nanotechnology and free trade of agricultural commodities. Additional financial support has been secured from both UK and US funders , with research outputs feeding into broader scientific groups within the nanoscience field. Researchers have developed close communication across organizations, taking advantage of career changes and academic movement between organizations to further build networking opportunities and to grow the research community. Indeed, these difficult to quantify developments may be some of the most important outcomes of this transatlantic program. Notably, the program has substantially advanced the understanding of how nanomaterials enter and move through the environment, how they transform, and how they may affect human health and ecosystems. Researchers have characterized the functional relationship between the nanomaterials physicochemical properties, their toxicity, and effect on organisms, and demonstrated this relationship is amenable to modelling. A key output from this program has been the development of models that characterize the fate of nanomaterials through the environment and predict the impacts they might have on the environment and human health.Although these collaborations have substantially advanced the knowledgebase, additional work is needed to further progress. The US-UK transatlantic program offers an ideal funding model to enhance progress while effectively making use of scarce resources. An important development is that future funding models should include a more direct link between innovation and risk-related research. These are two cognate areas that are often separated for structural reasons but their interdependency and integration is essential for the safe and sustainable development of nanotechnology. Results reported here point to important research questions that future work will need to address:Are current analytical methodologies suitable for parameterizing and validating models? If not, what further methods can be developed?Can existing models be applied to realistic exposure scenarios? If not, what modifications are required?Can existing models be applied to the next generation of nanomaterials? If not, how can these models be optimized?


Owing to child survival initiatives around the world in the 1970s and 1980s, a dramatic rise in the population of adolescents has been seen, especially in the developing countries. A quarter of world's population in 2012 comprised adolescents and young adults; of these, 90% lived in low- and middle-income countries. More recently, there has been a consensus on investing in adolescent health and development for the success of post-2015 developmental agenda. In this series of articles, we aimed to assess various interventions identified in our conceptual framework to evaluate their effectiveness in improving adolescent health. We took a systematic approach to consolidate the existing evidence. This article is an introductory article detailing the background, conceptual framework, and methodology used for synthesizing evidence, followed by seven articles summarizing evidence on interventions for sexual/reproductive health, nutrition, immunization, mental health, substance abuse, and accidents/injury. The concluding article of the series summarizes the findings of the all the previous articles in the series and the relevance of the evidence for action in the post-2015 Millennium Development Goals era along with evidence gaps and future research priorities. Adolescence is a critical age group as this is a period to develop specific expertise and hone individual skills to enter the mainstream workforce and contribute to the economic productivity. It is also a period when major changes in health and health-related behaviors such as smoking and substance abuse, unsafe sexual practices, poor eating, and lack of exercise occur, which may substantially impact health outcomes in later life. Due to the success of child survival initiatives over the last few decades, there has been a dramatic rise in the population of adolescents especially in low- and middle-income countries (LMICs) There is an unacceptable rate of mortality among adolescents, as an estimated 1.3 million adolescents died in 2012; 70% of these deaths occurred in Africa and Southeast Asia Globally, around 16 million babies are born to adolescent girls between the ages of 15 and 19 years Adolescence and young adulthood accord with key changes in health and its determinants later in life. The Lancet Adolescent Health series in 2012 reported that adolescents are more exposed to substance abuse, sexually transmitted infections, and other risks than in the past, in addition to facing other emerging challenges such as social media The purpose of this extensive review of eight articles The newly developed agenda for Sustainable Development 2030 has recognized a need for greater accountability especially for the Global Strategy for Women's, Children's and Adolescents' Health Various individual and general risk factors throughout the life cycle can have implications at any stage of the life cycle. The various stages of the life are not independent of each other and impacts early in life are carried to the next stage of life while some can also have intergenerational effects. We will not divulge further into this as the purpose of this series of articles was to review the potential interventions which could alleviate the risk factors of the adolescent age group only and impact quality of life thereon. We focused on risk factors including risky sexual behaviors, unintended pregnancies, violence, risky driving (including speeding and drunk driving), undernutrition, obesity, infections, and mental health risks. Adolescent girls are two to five times more likely to die from pregnancy-related causes than women aged 20–29 years Smoking, drugs, and alcohol use are also a significant health concern among adolescents. Alcohol use is a major risk factor and accounts for 7% of the DALYs among 10- to 24-year-olds. Most regular smokers initiate smoking before the age of 20 years and develop the habit over a lifetime after they become addicted. Drug abuse is a contributing factor for unemployment, poor health, accidents, suicide, and mental illness We included a range of potential interventions including (1) sexual and reproductive health interventions ; (2) nutrition interventions ; (3) infections and immunizations ; (4) mental health interventions ; (5) substance abuse ; (6) injury prevention interventions ; and (7) interventions for adolescents living with chronic diseases.Outputs included immediate and direct results achieved immediately after implementing an intervention, and these included access to sexual health services, knowledge of sexually transmitted infections, improved dietary behavior, improved physical activity, increased immunization uptake, access to mental health services, delivery of suicide preventive services, awareness of substance abuse, reduction in mental health risk factors, reduction in negative behavior, and increased life and livelihood skills.Investments in adolescent health and well-being bring a triple dividend of benefits now, into future adult life, and for the next generation of children 1.Overview of systematic reviews: We conducted an overview of systematic reviews for interventions where recent systematic reviews existed;2.Updating existing reviews: We updated the existing systematic reviews if the existing review only included evidence before 2011;3.De novo review: For interventions where no reviews existed, we conducted primary literature search followed by a systematic review of existing literature.Our aim was to look at the holistic evidence around the interventions identified in our conceptual framework for which we took a systematic approach to consolidate the existing evidence through the following three methodologies in the order of our priority:Our primary focus was on interventions targeting adolescents from both LMICs and HICs and where possible report segregated impact of the selected interventions in various settings. Our aim was to report data for adolescent age group where available; however, for certain areas where we could not desegregate the data for adolescents and youth age groups, we have reported the combined results for adolescents and youth as representative of the population of interest. We did not apply any language restriction in our search. The methodology applied for each of the above three approaches are described in the following sections:We conducted an overview of systematic reviews for interventions where recent systematic reviews existed. We considered all available systematic reviews published between January 2011 and December 2014 on the interventions to improve adolescent sexual and reproductive health, nutrition, immunization, mental health, chronic diseases, substance abuse, and injury prevention. Our priority was to select existing recent Cochrane and non-Cochrane systematic reviews of randomized or nonrandomized controlled trials, which fully or partly addressed the interventions for improving adolescent health. Detailed examination of cross-references and bibliographies of available data and publications to identify additional sources of information was also done. A broad search strategy was used that included a combination of appropriate keywords, medical subject heading, and free text terms. Search was conducted in the Cochrane Library, Medline, and PubMed to identify recent systematic reviews on the predefined interventions in our conceptual framework. The project team set up a triage process with standardized criteria for primary screening. The abstracts (and the full sources where abstracts are not available) were screened by two abstractors to identify systematic reviews adhering to our objectives. Any disagreements on selection of reviews between these two primary abstractors were resolved by the third reviewer. After retrieval of the full texts of all the included reviews, data from each review were abstracted independently and in duplicate into a standardized form. Information was extracted on (1) the characteristics of included studies; (2) description of methods, participants, interventions, and outcomes; (3) measurement of treatment effects; (4) methodological issues; and (5) risk of bias tool. We extracted pooled effect size for the outcomes of interest with 95% confidence intervals (CIs). We assessed and reported the quality of included reviews using the 11-point assessment of the methodological quality of systematic reviews criteria  [41].We updated the existing systematic reviews only if the most recent review on a specific intervention was conducted before December 2011. For updating the existing reviews, we adopted the same methodology and search strategy mentioned in the identified existing review to update the search and find all the relevant studies after the last search date of the existing review. After retrieval of the full texts of all the articles that met the inclusion/exclusion criteria, data from each study were abstracted independently and in duplicate into a standardized form. Information was extracted on study design, geographical setting, intervention type and description, mode of delivery, and outcomes assessed. We then updated the estimates of reported outcomes by pooling the evidence from the new studies identified in the updated search and reported new effect size for the outcomes of interest with 95% CIs. We then assessed and reported the quality of included reviews using the 11-point assessment of the methodological quality of systematic reviews criteria  [41].We conducted de novo reviews of available evidence for interventions where no reviews existed. We considered all available existing randomized, quasirandomized, and before/after studies on the identified adolescent health interventions. The following principal sources of electronic reference libraries were searched to access available data: the Cochrane Library, Medline, PubMed, Popline, LILACS, CINAHL, Embase, World Bank's JOLIS search engine, CAB Abstracts, British Library for Development Studies at IDS, the World Health Organization regional databases, Google, and Google Scholar. Detailed examination of cross-references and bibliographies of available data and publications to identify additional sources of information was also performed. A broad search strategy was used for each review that included a combination of appropriate keywords, indexing, and free text terms. The titles and abstracts of all studies identified were screened independently by two reviewers for relevance and matching. After retrieval of the full texts of all the studies that met the inclusion criteria, data from each study were abstracted independently and in duplicate into a standardized form containing study design, geographical setting, intervention type and description, mode of delivery, and outcomes assessed.2 and I2; a low p value (<.1) or a large chi-square statistic relative to its degree of freedom and I2 values >50% were taken as substantial and high heterogeneity. In situations of high heterogeneity, causes were explored by sensitivity analysis and random effect models were used. Our major comparison was the intervention of interest versus standard or routine care, but wherever data permitted we also attempted to evaluate the relative effectiveness of the intervention of interest in LMICs versus HICs and gender-specific impacts. We summarized the evidence by outcome, including qualitative assessments of study quality and quantitative measures, according to the standard guidelines. A grade of “high,” “moderate,” “low,” and “very low” was used for grading the overall evidence indicating the strength of an effect on specific health outcome according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria We conducted a meta-analysis of individual studies and reported pooled statistics as the relative risk for categorical variables and standard mean difference for continuous variables between the experimental and control groups with 95% CIs. The pooled statistics were reported using Mantel–Haenszel pooled method or DerSimonian–Laird method where there was an unexplained heterogeneity. All analyses were conducted using Review Manager, version 5.3 , which is a freely downloadable software used for conducting meta-analysis and present the results graphically We have adopted three approaches for this review: (1) conducting an overview of systematic reviews; (2) updating existing reviews; and (3) conducting de novo reviews. Although an overview of systematic reviews builds on the conclusions of rigorous reviews of multiple quality intervention studies in different settings, avoids duplication of work, and allows for a much faster review, there are some potential limitations. The interventions on which primary data exist, but which have not been covered by a systematic review, will not have been included. Furthermore, an overview of systematic reviews relies on review authors' characterizations of the findings rather than on individual studies and therefore may be affected by selective reporting biases. It also misses upon studies not taken up by included reviews. However, we have quality rated the existing reviews for more transparency and conducted de novo reviews following a rigorous methodology. Furthermore, de novo reviews had to be conducted for interventions including sexual and reproductive health, micronutrient, and balance energy protein supplementation, nutrition interventions for pregnant adolescents, adolescent immunization, substance abuse, accidents and injury prevention, and adolescents living with chronic diseases since either no reviews existed or the existing reviews did not focus on the prespecified adolescent age group.•Improving Adolescent Sexual and Reproductive Health: A Systematic Review of Potential Interventions: This review assessed the impact of interventions to improve sexual and reproductive health, preventing teenage pregnancy, preventing female genital mutilation/cutting, and dating violence prevention •Interventions to Improve Adolescent Nutrition: A Systematic Review and Meta-Analysis: This review evaluated the interventions to promote nutrition and prevent obesity, micronutrient and balanced energy protein supplementation, and nutrition interventions for pregnant adolescents •Systematic Review and Meta-Analysis of Interventions to Improve Access and Coverage of Adolescent Immunizations: This review assessed the effectiveness of interventions to improve immunization coverage for human papillomavirus measles, MMR, varicella, rubella, and TDap among adolescents •Interventions for Adolescent Mental Health: An Overview of Systematic Reviews: This overview of reviews assessed the effectiveness of interventions for eating disorders, violence, anxiety, depression, and suicide and suicidal behavior among adolescents and youth •Interventions for Adolescent Substance Abuse: An Overview of Systematic Reviews: This overview of reviews assessed the effectiveness of interventions to prevent substance abuse among adolescent population •Interventions to Prevent Unintentional Injuries Among Adolescents: A Systematic Review and Meta-Analysis: This article reviewed evidence for interventions to prevent unintentional injuries among adolescents •Adolescent Health Interventions: Conclusions, Evidence Gaps, and Research Priorities: This concluding article of the series summarized findings of all the previous articles in the series and relevance of the evidence for action in the post-2015 Millennium Development Goals era along with evidence gaps and future research priorities This introductory article helps understand the background, rationale, and methodology along with the conceptual framework which has consolidated the work in discussion for the following articles. With this understanding of the conceptual framework and methodology, we aimed to evaluate the effectiveness of interventions for improving adolescent health through existing systematic reviews and de novo reviews in the following articles. This article is followed by the following seven articles:The core concept of this series of articles is to identify a set of interventions and delivery platforms which would help prioritize areas of action for the global community and individual countries alike, where they can focus on improving adolescent health and reduce mortality in the adolescent period. This would also identify the gaps in literature and areas where more evidence would be required. This would build on the increasing focus on improving adolescent health and well-being and support the achievement of women's, children's, and adolescents' health-related post-2015 new global framework of Sustainable Development Goals.


Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs.We searched PubMed, PubMed Central, Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal immunization, governmental health policy or programmes, and MICs. Two authors independently reviewed the full text of the references, which were assessed for eligibility using pre-defined inclusion and exclusion criteria. The search terms identified 1,165 articles and the full texts of 21 were assessed for suitability, with eight articles included in the systematic review. MICs are implementing PCVs at a slower rate than donor-funded low-income countries and wealthier developed countries. A significant difference in the uptake of PCV in lower middle-income countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is largely due to an unsuccessful process of “graduation” of MICs from GAVI assistance, an issue that arises as countries cross the income eligibility threshold and are no longer eligible to receive the same levels of financial assistance. A lack of country-specific data on disease burden, a lack of local expertise in economic evaluation, and the cost of PCV were identified as the leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned in the reviewed papers include the use of vaccine cost-effectiveness analysis and the provision of economic evidence to strengthen decision-making, the evaluation of the burden of disease, and post-introduction surveillance to monitor vaccine impact.The global community needs to recognise the impediments to vaccine introduction into MICs. Improving PCV access could help decrease the incidence of pneumonia and reduce the selection pressure for pneumococcal antimicrobial resistance.The online version of this article (doi:10.1186/s41479-017-0030-5) contains supplementary material, which is available to authorized users. Streptococcus pneumoniae is the major cause of morbidity and mortality associated with childhood bacterial pneumonia and is responsible for at least 18% of severe episodes and 33% of pneumonia deaths in children worldwide  AND [middle income country OR middle income countries OR developing econom*] (example of Ovid MEDLINE 1946 search syntax), with the search of terms limited to title and abstract. We found that adding specific words such as child, childhood and pediatric to the search removed useful papers, so we kept the search as wide as possible with regard to age.The following search terms and structure were used and modified according to the syntax requirements of the database concerned: ) ) . A similb [Hib]) . The maib [Hib]) ) now resb [Hib]) . MICs arb [Hib]) , 8.For the period 2010–2015, GAVI committed approximately US$1.9 billion through the pneumococcal Advance Market Commitment (AMC) to fund PCVs that are suitable for developing countries . Those cThe WHO has actively developed different programmes to help MICs with PCV implementation. The WHO Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) aims to reduce deaths from pneumonia to fewer than 3 children per 1,000 live births by 2025 . The WHOThe PAHO Revolving Fund, also known as the Regional Revolving Fund for Strategic Public Health Supplies, helps Latin American countries negotiate a lower cost of PCV through bulk procurement, technical assistance on supply management, and assistance with planning, procurement systems, warehousing and distribution, and quality assurance . PAHO’s The WHO MIC Task Force has committed to investing approximately US$20 million per year for the 2016–2020 period to support activities included in the MIC Strategy . It inclThe WHO Strategic Advisory Group of Experts on Immunization (SAGE) Global Vaccine Action Plan (GVAP) aims to make 2011–2020 the ‘Decade of Vaccines’ . Its tarThe international non-profit organization Program for Appropriate Technology in Health (PATH) is collaborating with private- and public-sector partners to advance the development of PCVs in LICs . In partIn 2015, Doctors Without Borders/Médecins Sans Frontières (MSF) launched a global campaign—‘A Fair Shot’— calling on GlaxoSmithKline (GSK) and Pfizer to slash the price of PCV in developing countries, including MICs, to US$5 per child so that more children can be protected, and to disclose what they currently charge countries for the vaccine . MSF belS. pneumoniae, including disease burden and cost-effectiveness analyses, will generate the data needed to define the economic saving of widespread PCV implementation and to monitor the ongoing impact of widespread PCV immunization at national level.With many initiatives aimed at improving access to vaccines predominantly being targeted only at LICs, MICs have a much slower rate of PCV uptake . The incThe first consequence of PCVs being licensed for use and yet not being added to the NIP is that there may be substantial use of PCV in the private sector. This creates a gap between richer and poorer classes with a consequent equity issue, especially since the poorest children tend to experience the highest disease burden. Disparities in access to vaccines are often poorly understood by decision makers, particularly in licensure or in implementation strategies for new vaccines. It is therefore important to apply pressure at national and regional level to ensure governments attempt to address these equity issues to help reduce child morbidity and mortality from pneumonia.Since the cost per dose for PCVs is among the highest of the routine childhood immunizations, enhanced international advocacy on behalf of MICs for greater flexibility on pricing, and more rational procurement mechanisms for PCVs are critical actions. In particular, the lack of competition among manufacturers is a substantial barrier to reduction of vaccine cost. In fact, only two manufacturers, Pfizer and GSK, license and produce the two currently used PCVs—PCV13 and PCV10, respectively. Moreover, currently 60% of all GAVI-procured vaccines are manufactured in India. Through a recent partnership, GAVI and the Government of India will work together to create a more sustainable vaccine manufacturing base within India, ensuring valuable supplies for the children living in all 72 other GAVI-supported countries . InternaIn recent years, the anti-vaccination movement has become more vocal and even hostile , 40. It S. pneumoniae are of international concern and were noted in a 2013 ‘Threat report’ issued by the US Center for Disease Prevention and Control (CDC) [S. pneumoniae-related resistance after implementation of PCV programmes [It is in the interests of the international community to be more aware of the immunization issues faced by many MICs. Uneven global uptake of PCVs will affect serotype dynamics and spread of antimicrobial resistance, which will have an impact beyond the borders of countries without widespread PCV immunization. Levels of resistance in ol (CDC)  and therol (CDC) . There hogrammes , 44.Donors and non-governmental organizations (NGOs) can contribute towards building capacity in public health surveillance by offering technical assistance in strategy and execution of widespread epidemiological surveillance towards informing immunization policies. This is crucial as the dynamics of pneumococcal epidemiology are complex and studies need to be well designed and the data properly analysed to optimize the quality of data that eventually feeds through to informing vaccine policy.Additionally, MICs should be supported in identifying and initiating discussions with regional and local organizations with expertize in the planning, logistics and training required before implementing PCVs into a NIP. A successful example of this support model is the PAHO Revolving Fund (described earlier), which assists Latin American countries in managing the range of activities required for the implementation of PCVs.To address and resolve the issue of poor implementation of PCVs in MICs, the authors suggest that MICs need to be considered as a whole group and collectively undertake a series of steps. MICs should undertake a mapping exercise of their procurement strategies and range of practices; build a central headquarters to collaborate with single countries; understand procurement challenges and opportunities; develop a structural framework for MICs to assess their own procurement systems; explore inter-country and pooled procurement mechanisms; and improve targeted collaborations between MICs and international funding organizations.A number of study constraints exist. First, there are a limited number of studies examining PCV policy. Second, the definition of MICs as a category is sometimes somewhat arbitrary, making analysis of the MIC data difficult. Gaps also exist in the available literature, which combined heterogeneous studies. The methodology used and the article types of the selected papers were also heterogeneous, so that very few quantitative data can be extracted from literature. The study examined grey literature for evidence of unpublished data or studies, but, given the complexity of grey literature, publication bias can be present. There are also many consultations, national and regional meetings and projects  which aThe MICs are slowly implementing PCVs. The global community needs to recognise the barriers to PCV use in many MICs and respond to the situation by increasing scientific, financial, procurement and logistical support to broaden PCV access in MICs. MICs themselves need to strengthen decision making on pneumococcal immunization policy and to mobilize national political will and financing to reduce a significant, largely preventable disease burden, for the benefit of their populations and in the interests of wider international public health.


Evidence is mounting to suggest a causal relationship between the built environment and people’s physical activity behaviours, particularly active transport. The evidence base has been hindered to date by restricted consideration of cost and economic factors associated with built environment interventions, investigation of socioeconomic or ethnic differences in intervention effects, and an inability to isolate the effect of the built environment from other intervention types. The aims of this systematic review were to identify which environmental interventions increase physical activity in residents at the local level, and to build on the evidence base by considering intervention cost, and the differential effects of interventions by ethnicity and socioeconomic status.A systematic database search was conducted in June 2015. Articles were eligible if they reported a quantitative empirical study  investigating the relationship between objectively measured built environment feature(s) and physical activity and/or travel behaviours in children or adults. Quality assessment was conducted and data on intervention cost and whether the effect of the built environment differed by ethnicity or socioeconomic status were extracted.Twenty-eight studies were included in the review. Findings showed a positive effect of walkability components, provision of quality parks and playgrounds, and installation of or improvements in active transport infrastructure on active transport, physical activity, and visits or use of settings. There was some indication that infrastructure improvements may predominantly benefit socioeconomically advantaged groups. Studies were commonly limited by selection bias and insufficient controlling for confounders. Heterogeneity in study design and reporting limited comparability across studies or any clear conclusions to be made regarding intervention cost.Improving neighbourhood walkability, quality of parks and playgrounds, and providing adequate active transport infrastructure is likely to generate positive impacts on activity in children and adults. The possibility that the benefits of infrastructure improvements may be inequitably distributed requires further investigation. Opportunities to improve the quality of evidence exist, including strategies to improve response rates and representativeness, use of valid and reliable measurement tools, cost-benefit analyses, and adequate controlling for confounders.The online version of this article (10.1186/s12966-017-0613-9) contains supplementary material, which is available to authorized users. Physical activity is fundamental to human health and wellbeing . InsuffiA growing body of evidence shows clear associations between the neighbourhood built environment and physical activity behaviours , 11. SpeMcCormack et al.  systematRelationships may differ depending on the physical activity construct of interest  and the type of intervention , 28, 29.Relationships may also differ by population group  . AssociaThe quality of the built environment may be an important contributor to health inequalities, especially by influencing opportunities for active transport. To the authors’ knowledge, only one systematic review published to date has considered the impact that sociodemographic factors may have on the efficacy of built environment interventions . In theiTransport infrastructure is expensive but given the substantial economic burden caused by physical inactivity , built eOften, changes in the built environment, experienced either by changing residential location or by intervention in a familiar setting, do not occur in isolation. For example, infrastructural interventions may have associated social media campaigns or supplementary programmes to support behaviour change . It is cNotwithstanding frequent calls for research to understand causality , 28, 39,Some of the difficulties faced in assessing this broad evidence base include variable study quality, insufficient (or no) quality assessment of articles included in reviews , a narroFor these reasons, we believe it is timely to re-examine the evidence base, with a focus on updating and improving on previous reviews, by: (1) only including studies where causality can be implied, (2) considering intervention cost, (3) examining whether intervention effects differ by ethnicity or SES, (4) conducting rigorous article quality assessment, (5) including all age groups and physical activity behaviours, and (6) attempting to isolate the effect of the built environment from other interventions occurring in studies. Our aims are to: (1) conduct a new systematic review to identify which environmental interventions increase physical activity in residents at the local level, with the goal of informing future policy and practice in community design; and (2) to build on the limited evidence base on the effectiveness of built environment interventions for influencing health inequalities by systematically exploring the effectiveness of these interventions by ethnicity and SES.https://www.crd.york.ac.uk/prospero/] and published on figshare [The review protocol was prepared following the PROSPERO International prospective register of systematic reviews protocols [figshare .Articles were eligible if they reported a quantitative empirical study ) investigating the relationship between objectively measured built environment feature(s) and physical activity and/or travel behaviours in children or adults. Qualitative studies, or those that did not measure change in both the independent and dependent variables were excluded. For trials, no control group was required for the study to be included in the review.A systematic search of Scopus, Ovid , ProQuest Science, ProQuest Social Science, and the Transport Research International Documentation database , was conducted by the lead author (MS) in June 2015. Databases were identified in consultation with a subject-specific librarian, and the wider research team comprising specialists in transport, built environments, physical activity, active transport, epidemiology, and health. We acknowledge the value of grey literature in some circumstances but did not include studies reported in this form in this study. We sought the most robust evidence available, ensuring our methods were as robust and replicable as possible , and redKeyword searches of article abstracts and titles were conducted using three categories: 1) environments, 2) physical activity or travel modes, and 3) natural experiments, or prospective, retrospective, experimental, or longitudinal. Search terms were identified from MeSH subject headings in PubMed, previous similar reviews , 12, 46,Titles and abstracts of articles were screened by the lead author and included if they met the eligibility criteria. Where it was unclear whether articles met the inclusion and exclusion criteria from the abstract and title, full-text articles were sourced. Where bibliography searches identified article titles as possibly relevant, article abstracts were sourced and screened using the above criteria. All processes  were duplicated by a co-author (JH) with a random selection of 10% of each dataset , 48. AnyFor the purposes of this examination, a relatively broad definition of built environment was used, with the aim of identifying and understanding the range of modifiable factors in the external neighbourhood environment that may impact people’s physical activity or travel behaviours. Accordingly, ‘built environment’ encompassed either interventions or changes occurring at the individual level , or at the local, neighbourhood, or town scale. Measures were all objective and included geographic information systems-derived variables , community infrastructural or streetscape intervention typologies , natural or built aesthetic factors in the neighbourhood environment , and measures of other relevant environmental supports for physical activity or active travel . Recognising the contribution that public transport use can make to physical activity accumulation , 50, stuLikewise, a broad approach was taken to defining physical activity for this review – encompassing all types and dimensions of self-reported or objectively assessed physical activity . Physical activity could be assessed retrospectively, prospectively, using repeated cross-sectional surveys or direct observation, or before and after an intervention. While acknowledging the limitations of recall, well-designed retrospective studies offer a “plausible alternative to prospective longitudinal data collection”  due to tA study-specific data extraction form  as employed in previous similar reviews [Strength of evidence was determined using the  reviews , 46, andThe key outcomes of interest were physical activity , active transport (self-reported or observed), and visitation to or use of a setting . Findings were collated for each of these outcome measures and considered separately by population subgroups . Findings were also summarised in the context of study quality to gauge risk of bias and understand the strength of evidence provided.Figure n = 8), followed by uncontrolled repeat cross-sectional studies and uncontrolled longitudinal studies (both n = 6). Almost three-quarters (71%) of studies were conducted in the USA, with the remainder from Australia (n = 4), and Belgium, England, Scotland, and New Zealand . A majority of studies focused on all age groups (n = 13) or adults only (n = 12). Three (11%) focused on children and no studies focused specifically on older adults. Intervention types varied widely, but predominantly involved infrastructural interventions for facilitating walking and cycling . Park and playground improvements or development also featured regularly. Walking for leisure or transport was assessed in seven studies, cycling in two, and overall active transport in six studies. Where observation of active transport occurred, two studies directly observed cyclist counts only, and two undertook counts of pedestrians and cyclists.Key characteristics of studies included are provided in Table Study quality assessment results are provided in Table Four studies investigated whether built environment effects differed by ethnicity/race or SES, using a range of different approaches. The iConnect CBA study of new walking and cycling routes in three UK municipalities over two years found no significant interaction between the intervention and education, income or employment when using walking and cycling as the outcome . When exA randomized controlled trial of the effects of Los Angeles park improvements informed by community engagement found a significant increase in the number of white park users, but no significant changes for black, Hispanic or other users . InstallInterventions involving multiple streetscape improvements on active transport in children, and on physical activity in adults , 64Installation of park or playground equipment and active transport and physical activity in adults , 63Multiple component park renovations on children’s physical activity (for children of lower body size only) Temporary road closures and provision of play equipment on children’s physical activity Increased density of recreation facilities in the neighbourhood on physical activity in adults Table The aims of this systematic review were to provide an update on the evidence for the impact of the built environment on physical activity behaviours, and to systematically explore the effectiveness of these interventions by ethnicity and SES. Drawing from best practice, we took a systematic approach to identifying and screening literature, data extraction, and quality assessment of relevant literature.Findings showed a consistent positive effect of walkability components, provision of quality parks and playgrounds, and installation of or improvements in active transport infrastructure on active transport, physical activity, and visits or use of settings. Impacts on activity dimensions were observed in line with expectations  . AdditioMost analyses found no statistically significant differences in intervention effect by ethnicity or SES. However, one study found that new walking and cycling routes were used more by people with higher incomes, higher educational level and by people who were currently employed. Another study of park improvements found increased number of white users, but no significant change for black, Hispanic or other park users. Although these two studies provide a limited basis from which to draw inferences, the possibility that infrastructure improvements may predominantly benefit socioeconomically advantaged groups warrants further exploration in future evaluations.As identified in previous reviews, there was substantial variability in the methodology, measures, and analytical processes used to evaluate the impact of environmental interventions. Overall, this made comparisons between studies and intervention delivery approaches difficult. In part, this variability may be a by-product of the significant differences in intervention typologies and associated research designs. There remains, however, a need for improved study quality, which may mitigate this somewhat . Our quality assessment rated three-quarters of included studies as weak. Studies were frequently limited by lack of representativeness and generalisability.In most cases, blinding was not described in studies. Following the scoring protocol of the EPHPP, this earned a “Moderate” rating. It is worth noting there are ethical issues to be considered with participant blinding (such as informed consent), and that these can sometimes conflict with quality assessment criteria, where blinding is desirable to reduce bias associated with participant self-report or reactivity . We chosFew studies comprehensively controlled for confounders. While sex and age were commonly controlled or stratified for in analyses, only some included robust measures of SES or ethnicity. Depending on study design, area-level SES (and ethnicity characteristics) may suffice in order to mitigate challenges around collecting these data at the individual level. In their systematic review, Schule et al.  recommenIssues around contamination and consistency across intervention sites were rarely considered and were not controlled for in any analyses. Future studies would also benefit from considering neighbourhood self-selection as a possible confounder. In their systematic review, McCormack et al.  reportedOverall, there was a lack of research specific to children or older adults. It is possible that the adult-centric approach to characterising built environments may not be sufficiently capturing environments that matter to younger populations. For example, in their earlier review, Sugiyama et al.  found noIn keeping with Hunter et al. , reportiCompared with infrastructural interventions, relocation studies are less hindered by infrastructural cost. RESIDE is perhaps the first study of its kind – a natural experiment involving longitudinal data collection with new residents of new housing developments . The stuThe substantial inconsistency in timing and number of follow-up measures post exposure  limits a clear understanding of the impact of the built environment on physical activity. In their systematic review of natural or quasi-experiments, Mayne et al.  found thFinally, it is possible that publication bias affected the balance of studies included in this review. In general, registration or public release in other forms of study protocols prior to the publication of findings provides a check on selective reporting of study results.This systematic review focused on physical activity behaviours and use or visitation of settings, and did not include more distal health measures such as body size . While tThe broad inclusion criteria used here are a strength, drawing on studies across all quality assessment categories as well as considering findings in light of study quality. However, the exclusion of grey literature could have been a limiting factor, in that it is possible that significant new lines of inquiry might have been overlooked.While acknowledging the important role of perceptions on the relationship between the built environment and activity behaviours , 74, thiOur focus was on being able to isolate the effect of specific built environment features or interventions, thus studies that employed aggregate measures  were excluded from this review. A range of robust studies exist in the field that have utilized aggregate measures , 81. TheThere have been calls for more systematic approaches in reviews in this field . This stThe systematic and comprehensive approach to examining study quality and contextualising findings in light of study quality in this review adds strength to the evidence base for the positive impact of built environments on physical activity behaviours, active transport, and visits to/use of activity settings. Improving neighbourhood walkability, quality of parks and playgrounds, and providing adequate active transport infrastructure is likely to generate positive impacts on activity in children and adults. Specifically, findings from the current review suggest that the following show promise for increasing active transport and physical activity levels in children and adults: multiple streetscape components for walking or cycling  and parking bays; creating safe places to walk); bike boulevard/lane installation; new greenways; traffic free bridges and boardwalks; installation of fitness/playground equipment; multiple park renovations ; removal of park/playground seating; retrofitting existing spaces into pocket parks; temporary road closures and play equipment; access to and availability of public transport; higher residential, destination, and recreation density; increased street connectivity; and increased land use mix. The strongest evidence existed for multiple streetscape components , installation of fitness equipment (adult PA and AT), temporary road closures and play equipment (child PA), and recreation facility density (adult PA).Numerous limitations in the evidence base exist. In particular, the possibility that the benefits of infrastructure improvements may be inequitably distributed requires further investigation. Notwithstanding the significant challenges in terms of research design, many opportunities to improve the quality of evidence are clear, including strategies to improve response rates and representativeness, use of valid and reliable measurement tools, cost-benefit analyses, and adequate controlling for confounders.Additional file 1:Search terms. (DOCX 11 kb)Additional file 2:Data extraction form. (DOCX 13 kb)Additional file 3:Adaptations made to the Evaluation of Public Health Practice Projects Quality Assessment Tool (EPHPP) scoring criteria. (DOCX 25 kb)Additional file 4:Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies - Component Ratings of Study. (DOCX 12 kb)


This conference is a continuation of a series of meetings, which began with the first International Genomic Medicine Conference  followed by the second International Genomic Medicine Conference . The 3rd IGMC meeting presented as a timely opportunity to bring scientists from across the world to gather, discuss, and exchange recent advances in the field of genomics and genetics in general as well as practical information on using these new technologies in different basic and clinical applications. The meeting undoubtedly inspired young male and female Saudi researchers, who attended the conference in large numbers, as evidenced by the oversubscribed oral and poster presentations. The conference also witnessed the launch of the first content for npj Genomic Medicine, a high quality new journal was established in partnership by CEGMR with Springer Nature and published as part of the Nature Partner Journal series. Here, we present a brief summary report of the 2-day meeting including highlights from the oral presentations, poster presentations, workshops, poster prize-winners and comments from the distinguished scientists.The Third International Genomic Medicine Conference (3 The 3rd IGMC provided a focused and in depth view of the latest research findings relating to cancer, genetics, genomic medicine, reproductive medicine, ageing, metagenomics and metabolomics, personalized genomics, biobanking, bioinformatics, along with many other interesting topics. At least 500 leading international researchers, renowned national scientists including those from KAU dedicated scientific faculty, participated proactively presenting their latest research findings. All the recognized universities and research organizations in Saudi Arabia including CEGMR, Center of Innovation in Personalized Medicine (CIPM), King Fahd Medical Research Center (KFMRC) and King Abdulaziz City for Science and Technology (KACST) participated. The following countries were represented: Canada, Egypt, Germany, Japan, Qatar, Spain, Switzerland, Tunisia, Turkey, United Kingdom (UK), and United States of America (USA).Given the resounding success of the Second International Genomic Medicine Conference . In addition, a significant number of private companies attended the conference and took advantage of the meeting to present their state-of-the-art products, and services supporting genome research. Workshops  were organized over 3 days following the 2-day symposium. Here, we report the overall events and activities of the meeting including oral presentations, poster sessions, workshops, poster prize winners and comments from highly distinguished guest speakers about the meeting.One of the major events of the meeting was the announcement and launch of the first issue of the th of November, the conference began symbolically with an opening ceremony and welcome reception proceeding with the recitation of Holy Quran. The session was chaired by Professor Adeel Chaudhary, Deputy Director at CEGMR and Vice Dean of the Faculty of Applied Medical Sciences, KAU. On the stage, the Chief Guest, His Highness Vice President Professor Adnan Zahid and the Director of CEGMR, Professor Mohammed Al-Qahtani were seated to accord the occasion. A large number of foreign delegates, guests of honor, scientists, faculty and participants from a variety of institutes were in attendance. Professor Mohammed Al-Qahtani, gave a welcome address  from the Saudi Food and Drug Administration (SFDA) who presented a detailed view of the workings of the organization, its aims and how all members of the SFDA organization are continuously trying to help and facilitate the mission of scientists at the research centers within Saudi Arabia. The welcoming session ended with a presentation by Dr. Magdalena Skipper, the npj Executive Editor, NPG, UK who presented the model of the partnership between the NPG and CEGMR, which has led to establishment of the first npj journal in the Middle East, npj Genomic Medicine (http://www.nature.com/npjgenmed/). This fruitful partnership between NPG and KAU has led to establishment of a second npj journal, npj Climate and Atmospheric Science, http://www.nature.com/npjclimatsci/. Later, the Editor-in-Chief Dr. Stephen Scherer of npj Genomic Medicine announced the launch of the first issue of the journal. After Dr. Skipper’s talk the proceedings of the conference were declared open and all attendees settled to scientific business.The 3The second session on Day 1 was dedicated mainly to “Genomics of Cancer, Ageing and Complex Diseases” Table . This sede novo mutations near to de novo copy number variations residing on the maternal chromosome. He also discussed how to integrate epigenomic data with whole genome sequence data and interpret complex data through clustering approaches. He further emphasized the importance of performing WGS of 10,000 individuals with ASD and their family members and applying this data to diagnostic and drug treatment design [The keynote lecture was followed by a presentation by Professor Stephen Scherer from the Centre for Applied Genomics, Hospital for Sick Children and University of Toronto, Canada on “Genomic basis for autism spectrum and related disorders”. He explained the substantial contribution of non-coding variants to the aetiology of autism spectrum disorders (ASD) and highlighted the significance of using whole genome sequencing (WGS) for comprehensive genetic analyses. A novel observation shared was an increased frequency of t design .Professor Albert Fornace from the Lombardi Comprehensive Cancer Center, Georgetown University, USA then spoke on “Integration of metagenomics and metabolomics in gut microbiome research”. Professor Fornace presented his research group’s various discoveries using metagenomics and metabolomics strategies to understand the correlative nature of the microbe/host co-metabolism to distinguish the regulatory functions of microbiota in preserving the health of the host. He further explained the potential of host/microbial interaction studies to define causality, response to treatment, risk prediction, and keystone species to exploit as probiotics in diseases such as inflammatory bowel disease (IBD) or colonic inflammation (colitis) triggered by immune-radiotherapy.Professor Nobutaka Hirokawa from the Departments of Cell Biology and Anatomy, and Molecular Structure and Dynamics, University of Tokyo, Japan presented interesting talk titled “KIF2A regulates postnatal axons and its deficiency causes malformation of cortical development and epilepsy”. He presented his findings on the importance of Kinesin-13 super family protein 2A (KIF2A), an ATP-dependent microtubule destabilizer, in the development of precise neuronal circuits, prenatal cell survival, migration and the elongation of axons. He further described various studies to decipher the role of KIF2A in neuronal development using tamoxifen-inducible conditional KIF2A knockout mice. He showed that the loss of KIF2A led to hippocampal sclerosis, dentate mossy fiber (MF) sprouting, and recurrent excitatory circuits resembling but different from temporal lobe (TLE) and these phenotypes developed without excitation. More importantly, he showed that the conditional KIF2A granule cells displayed failed axon/dendrite differentiation, and developed multiple short axons throughout the entire molecular layer.Then Dr. Deema Hussain from KFMRC, KAU gave a presentation on “A unique integrated system to discern pathogenesis of central nervous system tumours”. Her presentation focused on the establishment of a unique integrated system to facilitate the analysis of multiple bio-parameters of distinct central nervous system tumours (CNST) such as meningiomas, astrocytomas, oligodendrogliomas, medulloblastomas and glioblastomas. She explained about generating cell lines from CNST for further genetic, biochemical, cytological and pharmacological analysis. She also elaborated further on the importance of gene expression profiling of uncultured tumour samples to enable identification of several novel prognostic markers for meningiomas, including the recently associated cancer stem cell marker called anterior gradient protein 2 homolog (AGR-2). Dr. Deema concluded that the integrated analysis approach was essential for the development of safe, efficacious and potent targeted therapeutic modalities for CNST.The final presentation of the second session on Day 1 was delivered by Dr. Heba Alkhattabi from CEGMR on “RPL27A, a novel target for miR-595 and its contribution to myelopoiesis via ribosomal dysgenesis”. She discussed the identification of several targets for miR-595 including a large ribosomal subunit RPL27A using a novel method. Dr. Alkhattabi explained that the down regulation of RPL27A triggered p53 activation, apoptosis and inhibited proliferation. More significantly, she showed that p53-independent effects were observed secondarily to a reduction in the ribosome subunit 60s with associated ribosome dysgenesis. In addition, RPL27A overexpression did not influence the p53 mRNA levels but enhanced proliferation. RPL27A knockdown in normal CD34+ cells specially inhibited erythroid proliferation and differentiation. Dr. Alkhattabi concluded that haploinsufficiency of miR-595 in Myelodysplastic Syndromes (MDS) patients with - 7/del 7q may contribute to disease pathogenesis via RPL27A modulation since miR-595 was significantly down regulated in these patients with −7/-7q anomalies.The final scientific session of the first day (Session III) was on "Genomics applications towards personalized medicine" Table  with allAlong similar lines, Professor Anna Goodeve from Sheffield Diagnostic Genetic Service, Sheffield Children's NHS Foundation Trust, UK, shared her experience on how next generation sequencing (NGS) and gene panels have extended diagnostic capability in analyzing blood related disorders. The haemostasis and platelet gene panel which included 13 genes and another panel consisting of 16 genes that are currently known to be associated with Fanconi's anaemia (FA) were sequenced using the Illumina MiSeq or HiSeq. Dr. Goodeve’s results revealed that the haemostasis and platelet panel enabled identification of pathogenic candidate mutations in 62 % of the patients. The FA panel led to the identification of biallelic mutations (33 %), heterozygous mutations (13 %), homozygous mutations (13 %), other gene mutations (7 %) and no mutations (33 %). She concluded that the use of NGS provides a single laboratory workflow for analysis of gene panels for different disorders and considerably reduces time to achieve a definitive diagnosis.In the final presentation of this session, Dr. Ashraf Dallol, from the CIPM/CEGMR at KAU, explained the usefulness of targeted sequencing of cancer mutational hotspots in combination with the Ion Torrent Personal Genome Platform in a cohort of colorectal cancer (CRC) cases from Saudi Arabia. CRC is a heterogeneous disease influenced by genetic and epigenetic variations acting as passengers or drivers of the tumor. Dr. Dallol showed that analysis of the mutational status of 2,800 catalogued somatic mutations in cancer (COSMIC) mutations of 50 oncogenes and tumor suppressor genes in CRC would enable understanding the genetic background for this cohort and thus pave the way to precision medicine (PM).Since the completion of the Human Genome Project in 2003, a significant increase in the number of Biobanks  has been observed worldwide. The main aim of establishing these banks was to support effective genomic research and personalized healthcare. Nowadays, Biobanks are considered as the main core around which OMICs research and advanced clinical applications are carried out to drive PM . Howeverrd IGMC “Biobanking in the Post-Genomic Era” session  scale to target specific rare and disease-specific variations was another major focus of the conference delivered by Professor Angel Carracedo from Legal Medicine Santiago de Compostela University, Spain. He showed that moving from GWAS-driven associations to causality is a key turning point towards personalized medicine. However, a further filtering step of the large number of associations revealed by GWAS with reduced heritability is necessary to identify causality or susceptibility targets. Professor Carracedo suggested new targeted re-sequencing of GWAS association targets in order to refine both the scale and mapping of the genomic hits. These identified hits would provide clues to decrypting the molecular pathways.Professor Carracedo’s talk was followed by that of Professor Hossam Faheem from Fujitsu Technology Solutions International, Japan who showed that several factors including computer science, medical informatics, Biobanking LIMS (Laboratory Information Management System), bioinformatics, biostatistics and OMICs datasets should be joined to tailor a clinical integrative analysis workflow of heterogeneous datasets in order to drive the current transition from OMICs-based science to OMICs-based healthcare. He showed that advanced computational tools such as the supercomputing facilities with superior memory to accommodate parallel and computationally intensive applications’ needs offer excellent solution which are now implemented at KAU (named as AZIZ supercomputer facility).The bioinformatics session ended with a presentation by Dr Sajjad Kareem from CEGMR who highlighted developing a new web application called E-GRASP which allows: (i) SNPs view including information about SNPid, PMID, P-value, chromosome, position, number of studies and phenotypes for each SNPs, (ii) studying view; which explains unique SNPs replication in each studies and phenotypes and (iii) evolutionary view which describes evolutionary information including E-value for SNP phenotype association, E-rank of the evolutionary rate and time span of the position retrieved from the “E-rank Web Server” for each SNP. Dr. Karim concluded that E-GRASP is a more representative database with additional information of SNPs replication and evolutionary scores, facilitating the comprehensive qualitative and quantitative analysis.st Century Session at the 3rd IGMC was dedicated to highlight the revolution in reproductive and developmental medicine due to the OMICs-based application that can offer successful and cost-effective solutions.The investigation of disease aetiologies requires a complex and multidimensional approach. Sufficient understanding of these diseases origins and susceptibility is an important prerequisite. Thus, investigation of germline genomic instability (mutations and epi-mutations) and its role in disease heritability and/or susceptibility during reproductive and embryonic phase will provide clues about diseases’ origin and relevant causative genomic variations. The Reproductive Medicine in the 21Dr. Aisha Elaimi from the CEGMR/KAU Table  highlighDr. Serdar Coskun from King Faisal Specialist Hospital and Research Center, Riyadh, KSA addressed the issue of the OMICs scale applications and their impact in preimplantation genetic testing (PGT), where only one or a few cells are available for genomic analysis. He showed that the development of single cell whole genome amplification (scWGA) technologies enabled obtaining sufficient high-quality DNA from the initial minute starting material . Dr. CosProfessor Ashok Agarwal, Center for Reproductive Medicine, The Cleveland Clinic, Cleveland, USA, focused his presentation on addressing new research into the causes of male infertility including proteomics which is the new frontier of research in male infertility as it allows the identification of numerous sperm-specific proteins. Prof. Agarwal concluded that proteomics provides a greater understanding of protein functions involved in sperm processes such as motility, capacitation, acrosome reaction and fertilization.The reproductive medicine session wrapped up with a presentation by Professor Eberhard Nieschlag, Center for Reproductive Medicine and Andrology, University Hospital of Muenster, Germany, who focused on the Klinefelter Syndrome (KS) and its relationship with infertility. He showed that the incidence of KS in the general male population is 1:500 and among 23,000 patients of the Center for Reproductive Medicine and Andrology at the University of Muenster, Germany is 1:52, whereas in Saudi Arabia the incidence is 1:11 in selected patients with azoospermia or sperm counts <5 mill/ml. Professor Nieschlag’s presentation drew the attention to the serious impacts of the KS on Saudi infertility patients.n = 48) enrolling in the workshops. The venue for training was provided by CEGMR at KAU and many of the workshops were overseen and delivered by highly distinguished, international faculty who participated in the IGMC conference in a number of capacities. The success of the workshops program demonstrated the desire and enthusiasm of many local researchers to extend their knowledge in different fields and further develop their professional capabilities.The scientific sessions of the 3rd IGMC were accompanied by eight workshops. These workshops offered the opportunity for local researchers to enhance their practical knowledge as well as to introduce the novice to the wide array of applications and cutting edge technologies available to researchers. The practical IGMC workshops covered a range of areas such as molecular cytogenetics in medicine, molecular genetics, flow cytometry in oncology, bioinformatics, high throughput DNA sequencing and microarrays. One additional workshop was introduced for the first time in the IGMC, the publication workshop, which was very well-received by the participants. Overall, the high demand for such wide range of training was demonstrated by the large number of applicants  was awarded to Olfat Al-Harazi from the Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA (Poster number 30) titled ‘’Breast Cancer Incidence and Genomic Signature in Young and Old Women in Saudi Arabia and Western Countries‘’. The second prize (4000 SR) went to Nezar Al-hebshi, Department of Preventive Dentistry, College of Dentistry, Jazan University, Jazan, KSA (Poster number 23) titled ‘’Mutational landscape of Arabian snuff-associated oral squamous cell carcinoma‘’. The third prize (SR 3000) was earned by Nada Salem from CEGMR/KAU, KSA (Poster number 105) titled: ‘’Integrated use of evolutionary information in GWAS reveals important SNPs in Asthma‘’.Dr. Muhammad Abu-ElmagdDr. Ashraf DallolProfessor Jerry W. ShayDr. Gauthaman KalamegamDr. Mourad AssidiProfessor Abdelbaset BuhmeidaDr. Farid AhmedProfessor Stephen W. SchererProfessor Bruce BudowleDr. Hans H. SchultenThis committee consisted of nine members whose role was to carefully review the abstracts, make final decisions on the acceptance or rejection of submitted abstracts, and to decide which abstracts would be presented either as a poster or as an oral presentation. The members of the scientific committee are as follows:rd IGMC abstracts’ and articles’ supplements was led by Dr. Muhammad Abu-Elmagd who worked as the editor of both supplements. The 3rd IGMC abstracts’ supplement was published in BMC Genomics . The articles' supplement containing 16 peer-reviewed articles was published in a number of BMC journals including BMC Genomics, BMC Medical Genetics, BMC Cancer and BMC Structural Biology. The final decision on accepting and rejecting manuscripts was made by the Executive Editor of BMC Genomics.Editing the 3Guest keynote speaker Professor Jerry W. Shay: ‘’This was by far the most successful International Genomic Medicine Conference that was held in Jeddah, November 2015. There was a very large number of attendees that led to many discussions about science enabling many new collaborations. The invited speakers were excellent, covering diverse areas of genomics and human disease. The organization of the meeting was simply outstanding. Everything worked from registration, the overall program and most importantly the poster sessions. As one of the judges of the poster sessions, I had many conversations with young scientists. Their excitement about their work was contagious and will certainly have a future positive impact for science in the Kingdom of Saudi Arabia‘’.The Director of the Centre for Applied Genomics, The Hospital for Sick Children and The Director of McLaughlin Centre for Molecular Medicine, University of Toronto, Canada, Professor Stephen Scherer: ‘’The meeting was memorable because all of the discussions were grounded in science and in data quality including interpretation of results. The session on Biobanking was very important since this can be done 'right' or it can be done 'wrong' and there needs to be scholarly discussion early on in decision-making. Perhaps, most importantly, I was energized by the excitement of the younger people participating at the meeting including many who traveled from remote regions of the Kingdom. There were many good lessons to be learned from the locals, national, and international participants‘’.The Director of the American Center for Reproductive Medicine, Cleveland Clinic, USA, Professor Ashok Agarwal: ‘’I am pleased to share my impressions of the Third International Genomics Medicine Conference organized by the Center for Excellence in Genomic Medicine Research at King Abdulaziz University, Jeddah, Saudi Arabia in November 2015. The meeting was nicely organized in a pleasant venue, it had a large number of attendees and a galaxy of highly recognized speakers from many parts of the world. The keynote lectures went really well; there was lively discussion after these talks. The presentation by local team of researchers was of high quality and a good indicator of future developments in the field of genomic medicine. I came back with good memories of the excellent scientific discourse, opportunity to meet and listen to both local and international scientists and most importantly the warm hospitality of the local organizing committee‘’.Genomic Medicine, a journal CEGMR/KAU has established in partnership with the Nature Publishing Group (NPG) that promises to expand publishing options in the Middle East and around the world. The conference workshops offered extensive training to the participants in a wide range of genomics tools and approaches. The take away message from most talks was that studying the population structure and health challenges confronting Saudi Arabia and by openly publishing the results would not only help people in this region, but also provide lessons for other countries around the world.The 3rd International Genomic Medicine Centre set a stage for the next round of planning and scientific investment in the area of individualized (precision) medicine in Saudi Arabia . The act


Ethnic differences regarding the percent of non-communicable diseases have been shown in Asia but the studies on Asian subgroups living in the western countries regarding percent of cardiovascular risk factors and dietary intakes have been scarce. Therefore we compared the percent of cardiovascular risk factors and dietary intakes between Javanese Surinamese who are originally from Indonesia and South-Asian Surinamese who are originally from India.Cross-sectional baseline data of the HELIUS  study were used, including data of 2935 Surinamese participants (197 of Javanese and 2738 of South-Asian origin) out of which 1160 participants (78 Javanese and 1082 South-Asian) additionally reported dietary intake data. Descriptive statistics were used to compare the two ethnic groups regarding cardiovascular disease, diabetes, obesity, hypertension and hypercholesterolemia; in addition, dietary intake of foods like vegetables, red meat, fruit, high fibre foods, low fibre foods, high fat and low fat dairy products, chicken and sugar sweetened beverages were also compared between the two groups. Binary logistic regression analyses were used to adjust for age and sex when comparing the two groups.South-Asian Surinamese had a significantly higher percent of abdominal obesity , cardiovascular disease  and diabetes  as compared with Javanese Surinamese after adjustment for age and sex. The percent of obesity (BMI), hypertension, and lipids was not significantly different between the ethnic groups. Javanese Surinamese had a significantly higher intake of red meat and a significantly lower intake of dairy products as compared with South-Asian Surinamese. Intakes of vegetables, grains, fish, fruits, tea and coffee did not significantly differ between the ethnic groups. Both groups showed intake of considerable amount of sugar sweetened beverages.Public health practitioners in the Netherlands and elsewhere in the world should take into account the ethnic subgroup differences within the broader groups like Asians when developing interventions related to health among ethnic minorities. Cardiovascular disease (CVD) is the leading cause of death among Asians . PreviouDiet is presumed to be a key lifestyle factor contributing to the increased risk of cardiovascular disease among the Asian population , 5. The Certain dietary items have a protective effect against cardiovascular disease, diabetes and obesity such as fruits, vegetables, fibrous foods and fish , 7. On tPrevious studies among Asian migrants living in western countries have pointed towards disease and diet differences among different Asian ethnicities , 15. HowSouth-Asian Surinamese and Javanese Surinamese originate from different countries, thus carrying different genetic and cultural backgrounds. At the same time these two ethnicities lived together in Surinam before migrating to the Netherlands. After the independence of Suriname in 1975, a large wave of Surinamese settled in Amsterdam. The present study addresses ethnic differences regarding the percent of non-communicable diseases and intake of dietary items between immigrants from the same country but with different cultural and genetic backgrounds. This information can help in developing tailored and culturally sensitive interventions to tackle non-communicable diseases. Therefore, the aim of this study is to compare the percent of cardiovascular risk factors and dietary intakes between two Asian groups, namely Javanese Surinamese and South-Asian Surinamese, living in Amsterdam, the Netherlands.What are the differences regarding percent of cardiovascular disease and related risk factors listed below between South Asian Surinamese and Javanese Surinamese?ObesityDiabetesHypertensionCholesterol levelsWhat are the differences in the intake of food items related to cardiovascular disease and related risk factors listed below between South Asian Surinamese and Javanese Surinamese?VegetablesFruitsRed meatFibrous foodsDairySugar sweetened beveragesThus we will answer following two research questions in this study.Cross-sectional baseline data of the HELIUS  study were used. The HELIUS study is a cohort study among the six largest ethnic groups living in Amsterdam, the Netherlands, and baseline data collection started in January 2011. The overall aim of the HELIUS study is to examine the health disparities across different ethnic groups and its causes. The population, aged 18–70 years, was randomly sampled from the Amsterdam municipality register, stratified by ethnicity . More details on the HELIUS study design have been published elsewhere . For the2 and <27 kg/m2, and obesity as BMI ≥ 27 kg/m2 based on appropriate cut-off points for Asians [Anthropometric measures were performed using standardised protocols . BMI wasr Asians . Waist cr Asians .Prevalent cardiovascular disease (CVD) was defined as the presence of intermittent claudication, possible infarction, and/or angina pectoris according to the Rose questionnaire . DiabeteFood intake was measured using ethnic specific FFQs that were designed for the HELIUS study . The FFQThe food groups were combined as follows: ‘Vegetables’ consists of all fresh, frozen, canned vegetables not including legumes or potatoes; ‘fish’ comprises of fatty and lean fish, crustaceans and molluscs and ‘red meat’ includes all red meat including organ and minced meat. Low fibre and refined grains consists of all low fibre bread, crackers, breakfast cereals, pasta, rice, noodles, pancakes; high fibre products and wholegrain cereals consists of all high fibre bread, crackers, Breakfast cereals, pasta, Bulgur and rice; sugar sweetened beverage comprises of sweetened fruit drinks, cordials, soft drinks, energy and sport drinks, ice lollies; high fat dairy products group is made up of high fat milk, milk-based puddings, yoghurt, ice cream, cream, cheese; low fat dairy products group comprises of reduced and fat free milk, yoghurt, puddings and cheese; fruit consists of all fresh, frozen or canned fruits; fruit juices consist of unsweetened and fresh juices.Descriptive statistics were used to calculate means and percentages for demographic variables such as age, sex, marital status, educational level, gender and disease variables like CVD, diabetes, hypertension and hypercholesterolemia. Dietary variables were not normally distributed, therefore we reported medians and inter quartile ranges. We tested for statistical significant differences in dietary intakes between Javanese Surinamese and South-Asian Surinamese using Mann–Whitney test. Furthermore, binary logistic regression analyses were used to analyse the differences in disease percent between South-Asian Surinamese and Javanese Surinamese adjusted for age and sex. Data were analysed using SPSS, version 21.Table Although mean BMI or general overweight/obesity did not differ between the two groups Table , South-AJavanese Surinamese reported a significantly higher intake of red meat as compared to South-Asian Surinamese Table . South-AOur study found that South-Asian Surinamese had a significantly higher percent of central obesity, self-reported cardiovascular disease and diabetes as compared to Javanese Surinamese after adjustment for age and sex. South-Asian Surinamese also had a significantly lower intake of red meat and significantly higher intake of dairy products as compared to Javanese Surinamese. No significant differences were observed in the percent of general obesity, hypertension, lipid profile and the intake of other dietary variables.Studies from Asia have found that different ethnic groups within Asia like Indians and Indonesians have differences regarding the prevalence of cardiovascular risk factors –30. In IJavanese Surinamese and South-Asian Surinamese originally migrated from the region of Southeast Asia and South Asia, respectively, to Surinam and then to the Netherlands. Southeast Asia comprises of countries like Philippines, Malaysia, East Timor, Indonesia, Brunei, and Singapore whereas South Asia comprises of countries like India, Pakistan, Bangladesh, Sri Lanka and Nepal. Javanese Surinamese were brought from the Java region in Indonesia and South-Asian Surinamese were brought from the modern day Indian states of Bihar, Utter Pradesh and adjoining areas by Dutch to work on sugar plantations in Surinam in late 18th and early nineteenth century. The mass migration of Surinamese to the Netherlands occurred after 1975, when Surinam announced independence from the Netherlands; more than hundred thousand Surinamese migrated to the Netherlands at that time. Most of these Surinamese settled around big cities in the Netherlands including Amsterdam, Rotterdam, Utrecht and Den Haag. There are 148,443 South Asian Surinamese and 73,975 Javanese Surinamese living in Surinam and there are 151,000 South Asian Surinamese and 22,000 Javanese Surinamese living in the Netherlands –22.The differences in CVD risk factors and dietary intakes between South Asian Surinamese and Javanese Surinamese, however, cannot be explained by their migration history to and from Suriname or by socio-economic factors. Both ethnic groups migrated to Suriname as contract workers in the late nineteenth century to fill labour gaps after the abolition of slavery. Subsequent migration to the Netherlands followed a similar trajectory for both groups; voluntary migration after the independence of Suriname. In the Netherlands, the groups have had the advantage of speaking the Dutch language. Currently there are 350,000 Surinamese living in the Netherlands, amongst whom first generation migrants generally have low levels of education and high unemployment rates –35, withWe studied the intake of some key dietary indicators and the results showed differences between the two ethnic groups. South-Asian Surinamese reported lower intake of vegetables and higher intake of dairy products (both high and low fat varieties) as compared to Javanese Surinamese; though both groups were using higher amounts of low fat dairy products as compared to high fat dairy products. Lower intake of vegetables is related to the increased risk of stroke . ExcessiPrevious studies of the diet of Surinamese origin migrants in the Netherlands have included South Asian and African Surinamese and have shown that these groups have similar dietary habits and fidelity to a typical Surinamese dietary pattern characterized by intakes of rice, noodles, chicken and fish . HoweverThe findings of our study need to be taken in light of several limitations. The number of Javanese Surinamese was relatively small, reflecting their relatively small representation within the Surinamese population in the Netherlands where approximately 40–45% are of South Asian origin and 10–14% Javanese , 45 out Our study found differences regarding the percent of cardiovascular risk factors and dietary intake between Javanese Surinamese and South-Asian Surinamese. South Asian-Surinamese had a significantly higher percent of abdominal obesity, self-reported CVD and diabetes, but did not differ in general obesity, hypertension and lipid profile. Both groups had a high percent of all cardiovascular related risk factors. Lower intake of vegetables and higher intake of dairy products among South Asian Surinamese as compared to Javanese Surinamese is a potentially unhealthy trend. In addition, higher intakes of red meat among Javanese Surinamese as compared to South Asian Surinamese should probably be regarded as unhealthy trend. The intake of low fibre refined grains and sugar sweetened beverages among both ethnicities could lead to an increased risk for the development of diabetes and other cardiovascular risk factors. CVD risks could be reduced by encouraging the intake of vegetables among South-Asian Surinamese and reducing the intake of red meat among Javanese Surinamese. In addition, the intake of low fibre refined grains should be reduced and replaced with high fibre whole grain foods. Similarly sugar sweetened beverages should be replaced with water among both groups.