Efforts to implement and take to scale highly efficacious, low-cost interventions to prevent mother-to-child HIV transmission (pMTCT) have been a cornerstone of reproductive health services in sub-Saharan Africa for over a decade. Yet efforts to increase access and utilization of these services remain far from optimal. This study developed and applied an approach to systematically classify pMTCT performance to identify modifiable health system factors associated with pMTCT performance which may be replicated in other pMTCT systems.Facility-level performance measures were collected at 30 sites over a 12-month period and reviewed for consistency. Five combinations of three indicators  were compared including a composite of all three, a combination of 1. and 3., and each individually. Approaches were visually assessed to describe facility performance, focusing on rank order consistency across high, medium and low categories. Modifiable and non-modifiable factors were ascertained at each site and ranking process was reviewed to estimate association with facility performance through unadjusted Chi-square tests and logistic regression. After describing factors associated with high versus low performing pMTCT clinics, the effect of inclusion of the 10 middle performers was assessed.The indicator most consistently associated with the reference composite indicator  was the single measure of antiretroviral prophylaxis and combined antiretroviral therapy. Lower performing pMTCT clinics ranked consistently low across measurement strategies; high and middle performing clinics demonstrated more variability. Association between clinic characteristics and high pMTCT performance varied markedly across ranking strategies. Using the reference composite indicator, larger catchment area, higher number of institutional deliveries, onsite CD4 point-of-care capacity, and higher numbers of nurses and doctors were associated with high clinic performance while clinic location, NGO support, women's support group, community linkages patient-tracking systems and stock-outs were not associated with high performance.Classifying high and low performance provided consistent results across ranking measures, though granularity was improved by aggregating middle performers with either high or low performers. Human resources, catchment size and utilization were positively associated with effective pMTCT service delivery. Sub-Saharan Africa bears a disproportionate HIV burden with 92% of HIV-positive pregnant women and 90% of all incident HIV cases in children globally . EffortsTo translate more efficacious regimens to effective pMTCT services, heterogeneous clinic-level facilitators and barriers that impact access and utilization must be addressed. By identifying modifiable health system factors associated with high and low-performing pMTCT systems, best practices can be disseminated and implemented to maximize the number of women and children reached with effective pMTCT services. Likewise, identified factors associated with poorer performance can be addressed across facilities to reduce their replication.PMTCT is a highly complex package of healthcare interventions that spans multiple stages of women's reproductive and children's developmental lifespan, and health services specific to these stages. To maximize the benefit to mothers and children, pMTCT is delivered in a timed sequence, or “cascade” that includes: attendance at antenatal care (ANC), HIV counselling and testing, provision of combined antiretroviral therapy (cART) – previously prophylactic antiretrovirals (ARVs) – safe delivery, administration of prophylactic ARVs for the exposed newborn through the breastfeeding period, safe infant feeding, infant follow-up including HIV testing, family planning and linkages to long-term HIV care and treatment , 6. CompIdentifying high and low-performing health facilities, and the drivers of performance, may highlight best practices associated with effective pMTCT service delivery in resource-limited settings for replication in other pMTCT systems. Two methodologies developed by systems management and behavioural sciences that utilize performance classification and exploit performance differentials to improve health system functioning and individual-level health behaviours include Lot Quality Assurance Sampling (LQAS) and Positive Deviance –12.LQAS includes the inspection of a small representative sample of a production lot, and if the number of defective goods in the sample exceeds a predetermined allowable number, the lot is rejected; otherwise the lot is classified as having acceptable quality .LQAS has been applied to the health sector to conduct rapid assessments of service coverage, the accuracy of health records, logistics and supply chain performance, training programs and the quality of facility management , 14–16. On the other side, positive deviance focuses on high performers to understand and amplify their traits, practices and characteristics across a broader population . By idenDespite their targeted use of either high (positive deviance) or low (LQAS) performance, neither adequately articulates a standardized approach for overall performance classification, which is challenging for cascade type services that span multiple arenas. Various methodologies assess the performance and/or effectiveness of pMTCT programs using single measures. Some of these include the uptake of ARV regimens during pregnancy and delivery as measured through program data ; the useThe objective of this study is to develop and explore a performance classification approach for health managers to use to identify modifiable health system factors associated with pMTCT performance. By describing this approach, we provide a novel model for pMTCT performance assessment that relies on routinely collected and reported data, and which can be used by health managers to identify modifiable factors associated with pMTCT performance to inform program improvement efforts.Activities were conducted as part of a multi-methods, cross-sectional study designed to identify modifiable and non-modifiable health systems factors associated with pMTCT service performance. The results presented here contributed to the parent study which will be conducted in three sub-Saharan countries by developing the health facility performance ranking approach as a first step for identifying systems-level factors associated with high and low-performing clinics.Thirty public sector health facilities with pMTCT services in three districts along the Beira corridor (the main transport route connecting the port city of Beira with Zimbabwe) in Sofala province, central Mozambique, were included in the study. Sofala has an estimated population of 1.8 million of which 47% live in the study districts of Beira city, Dondo and Nhamatanda . Sofala Since its introduction in 2002, pMTCT expansion has increased to reach 100% of all public sector clinics with ANC services in the three study districts  . The gapStudy facilities included all public sector health facilities that met the inclusion criteria of: 1) location in the three districts; 2) provision of pMTCT at ANC in the last six months; and 3) consent to participate in the study. Two facilities were excluded because they were unwilling to participate or had limited access due to flooding.Clinic data for pMTCT performance ranking were sourced from provincial program reports covering January–December 2012. Data were based on monthly health facility data, which in parallel is entered into the national health information system at the district level. Monthly facility-level data were assessed for availability by the study team to identify missing reports, and irregular or missing data were crosschecked with facility-level registries to ensure accuracy. Missing data were recovered for all measures except cluster of differentiation 4 (CD4) testing data, which were inconsistently available at the facility-level.Supplementary file). Descriptive, facility-level variables were identified through reviews of published literature on pMTCT and quality improvement, and the final list of facility characteristics was developed in consultation with provincial program managers and technical advisors [Data on health facility characteristics were collected using a survey developed for study purposes from November 2012 to January 2013  the proportion of pregnant women in ANC tested for HIV at their first visit; 2) the proportion of pregnant women with a positive HIV test at first ANC visit who had a CD4 test in pregnancy; and 3) the proportion of women with a positive HIV test in the first ANC visit accessing effective PPO or cART in pregnancy (versus testing at any time during pregnancy) because testing in the first ANC is standard as per Ministry of Health (MOH) guidelines, and because an effective pMTCT package should initiate as early in pregnancy as possible [Three performance measures were regnancy . HIV tespossible . Single-possible .n=30). First, each of the three indicators were estimated over a 12-month period . These individual indicators were then multiplied to generate the composite indicators. Facilities were ranked into three performance categories (high/middle/low) based on tertiles in the distribution of performance outcomes, rather than using a specific performance threshold level. Visual assessment was then used with one measurement strategy (HIV testing and ARV treatment and ARV PPO) defined as the reference strategy. This strategy was selected as the reference as it was composed of complete data sets and represented multiple steps in the pMTCT cascade.The 12 months of pMTCT cascade data were used to develop summary performance scores for each facility , and a second joining middle and low performers (to compare with high performers).In order to assess the value of comparing high Non-modifiable facility characteristics considered included facility type, classified into three levels – quaternary/tertiary hospitals, secondary hospitals and primary health centres, as well as catchment population sizes which were provided by provincial and district authorities. Additional non-modifiable factors collected included geographic location which was defined as urban/peri-urban/rural based on their location in Beira, Dondo or Nhamatanda municipalities (urban), in the outlying neighbourhoods of Beira (peri-urban), or outside of Beira, Dondo, or Nhamatanda municipalities  and year of pMTCT initiation which was provided by facility leadership.Modifiable facility level characteristics included staffing which was defined as the number of health workers of cadres most relevant to pMTCT service delivery , maternal and child health nurse, general nurse, midwife, custodian, social worker and activist). Distance to a laboratory with CD4 capacity was also considered modifiable as it could hypothetically be changed if CD4 capacity was introduced through new machines or new PIMA technology. This was estimated using driving distances between health facilities provided by provincial authorities.Other modifiable factors measures to describe pMTCT organization included integration with laboratory services , pharmacy services (medicines distributed via pharmacy or ANC/maternity) and outpatient care . Also, modifiable measures of community linkages included the presence of a mothers’ support group, whether community activists carried out patient tracking and whether health workers performed regular community outreach. General management practices were measured by the frequency of staff meetings. A list of essential medicines, supplies and materials related to pMTCT service provision was included in the factors list to assess the availability of key items over the preceding three months, as well as the length of stock outages, and was confirmed using stock registries. These were all deemed modifiable as innovations could be introduced to improve them at the facility, district or provincial level.Finally overall PMTCT service utilization was captured through four patient volume measures over the six-months before data collection, including the number of ANC consults, the number of postpartum consults, the number of institutional births and the number of modern family planning methods distributed.To refine the ranking procedures, we first explored whether the rank performance order for the 30 study facilities changed according to performance measurement , and a composite indicator multiplying indicators one, two and three for each facility (adding CD4 testing to the previous indicator). Visual assessment focused on the consistency of rank order across high, medium and low categories depending on ranking strategy, using the composite indicator of HIV testing and effective PPO or cART as the benchmark, with the top 10 performing sites shaded, the middle 10 in white and the bottom 10 dotted.Assessment of the impact of ranking process on facility-level characteristics associated with facility performance was carried out for three of the five ranking approaches, excluding CD4 testing data which were found to be less available and reliable. Unadjusted Chi-square tests for independence were performed to estimate the association between performance and health facility characteristics. For continuous variables, logistic regression for performance outcomes was used to quantify the magnitude and statistical significance of any associations with performance.versus low-performing pMTCT clinics, we assessed how the inclusion of the 10 middle-performing clinics affected the list of factors significantly associated with differential pMTCT performance. For this analysis, we developed ordinal logistic regression models including continuous clinic characteristics found to be significant in the bivariate analyses, and examined the magnitude of the associations between three-level  compared to two-level . Next, we aggregated low and middle-performing facilities to compare their characteristics to high-performing facilities, and then aggregated middle and high-performing facilities to compare their characteristics with low-performing clinics. This analysis ranked facilities using indicators one and three (HIV testing at first ANC and receipt of effective PPO or cART), as these measures were most available and measured multiple, essential steps for successful pMTCT.After describing factors associated with high Data analysis was performed using Stata v11.2 .Study procedures were approved by the Ethics Committee of the Mozambique MOH and were determined to be non-research by the University of Washington Institutional Review Board.The majority of health facilities were public sector, small to mid-sized primary health centres clustered in rural areas along the Beira corridor, with an average catchment population of approximately 28,000 inhabitants .Two hospitals were in the sample, including one quaternary-level referral hospital and one rural hospital. Over half of the facilities reported receiving no non-governmental organization (NGO) support, and almost 70% began pMTCT services between 2006 and 2008, during the push to fully extend pMTCT services to all health facilities with maternal child health (MCH) services nationwide. The mean distance between health facilities and their CD4 reference laboratory was 22 km (13.1 miles).Visual assessment of the effect of performance measures on ranking found a consistency among lower performing clinics, with more variability in rank order among higher performing facilities .Of the three indicators representing a single step of the pMTCT cascade, receipt of ARV PPO or cART for women identified as HIV positive at first ANC visit was the most consistent in rank order compared with the reference composite indicator of HIV testing and ARV therapy and ARV PPO. The single indicator with the most divergence from the composite measure was HIV testing at first ANC visit, which was high at all pMTCT clinics , and thus provided insufficient variability for characterizing high and low-performing pMTCT clinics. Though the proportion of women who received CD4 testing services was low (53.3%), it was included as a performance measurement strategy because at the time of study implementation, CD4 testing was a prerequisite to access care.Ranking strategy substantially impacted clinic characteristics associated with pMTCT performance .Using the two variable performance ranking approaches (HIV test at first ANC visit and ARV PPO or cART for mother), five factors were found to be significantly associated with higher pMTCT performance, including larger catchment area, higher number of institutional deliveries, availability of PIMA point-of-care CD4 capacity onsite, higher numbers of MCH nurses and higher number of MDs and NPCs. Longer lag time from polymerase chain reaction (PCR) blood draw to receipt of results at facility was associated with poor pMTCT performance, but shorter lag times were not associated with high-performing pMTCT clinics. Factors not associated with performance included clinic location, availability of NGO support, presence of a women's support group, active community-level patient tracking systems and stock-outs of essential testing supplies and medicines.Using maternal receipt of ARV PPO or cART as the single indicator for performance ranking, the presence of a support group for people living with HIV was also found to be significantly associated with higher performance; the remaining factors remained unchanged.Using a HIV test at the first ANC visit as the single indicator for performance ranking dramatically altered the factors associated with pMTCT performance, with only stock-outs of AZT in ANC remaining associated with high pMTCT performance. All other indicators that were positively or negatively associated with pMTCT performance were no longer significant in this analysis.Removing the 10 middle-performing clinics and comparing the magnitude of associations with three-level performance did not dramatically alter the results .With the exception of lag time between PCR blood draw and receipt of results at the pMTCT clinic, all additional explanatory factors remained significantly associated with performance.Aggregating the middle-performing clinics with the high or low-performing groups slightly impacted the characteristics significantly associated with pMTCT performance. Most notably, catchment area size was less strongly associated with performance when middle-performing clinics were aggregated with the low-performing group, though the strength and direction of the association was similar to the analysis omitting middle-performing clinics. Decreased waiting time between PCR blood draw and receipt of results at the clinic was more significant when the middle-performing facilities were aggregated with the high-performing group compared with the analysis omitting middle-performing facilities. For both the number of MCH nurses and number of MDs/NPCs, there was no meaningful difference in direction and strength of association when the middle-performing clinics were included in the analysis.In this article, we explore an approach to classify pMTCT performance based on routinely collected health systems data, coupled with additional data collection on modifiable and non-modifiable health systems factors, to identify best practices for pMTCT. We found that using two measures to classify pMTCT performance was preferable to one, though one measure (effective PPO or cART in pregnancy) provided sufficient performance variability to detect associations with health system factors. In general, combining critical individual components into a single composite measure – as part of a dashboard of measures – may facilitate system-level changes by highlighting the need for better care coordination and accountability across multiple providers or services . HoweverClassifying high and low performance provided consistent results across ranking measures, though granularity was improved by including middle performers in either the high or low-performing groups. In this analysis, human resource availability , catchment size and utilization were positively associated with effective pMTCT service delivery. A delay in PCR results was negatively associated with pMTCT service delivery. Notably, measures of community linkages were not associated with pMTCT service delivery across the ranking approaches.This study was limited by its relatively small sample of 30 facilities from one geographic location in one country, which affects the generalizability of the findings. Nonetheless, the methodology of using high and low performance shows promise, providing a framework that can be evaluated in other settings for HIV and non-HIV related services, and can be used to verify and add to the initial list of modifiable and non-modifiable factors associated with pMTCT performance.There are considerable on-going efforts to evaluate pMTCT programs at the global, country, and community level. These include novel techniques to estimate HIV-free survival using community surveys as well as more traditional health facility level surveys to assess the relationship between facility characteristics and pMTCT coverage across multiple countries , 45. TheThe principal strength of this study is its reliance on routine health information system data coupled with simple data collection that is feasible during routine supervision. By using health facilities as the unit of analysis , this study delves into broader determinants of effective pMTCT services that are under the control of health system managers, and can be modified to lead to broad improvements in service effectiveness. Furthermore, the simple analysis approach is geared towards district MCH managers to improve data use for pMTCT service redesign and enhancement, relying on strategies that are effective in their service delivery context.In this study, increased human resources were significantly associated with pMTCT performance, which is consistent with literature that has highlighted the importance of human resources for better health systems outputs and measures of population health impact , 47. ThiThe inability of individual measures  to capture a “high-performing” facility was likely due to insufficient variability in this measure across study facilities. Further research into the variability of pMTCT cascade measures in other settings is warranted to guide application of the ranking approach.The use of routine health information system data to classify health facility pMTCT performance represents an opportunity and a challenge in low resource, high-burden settings such as Mozambique. Using existing data sources reinforces routine information systems and can lead to investment by health workers in assessing and improving service delivery, though incomplete or inconsistent data can result in inconsistent rankings .This study supports using fewer, targeted performance measures for systems analysis. As reporting requirements increase to meet the expectations of funders, less time is available to use data for program improvements by district and frontline health managers. Targeting high and low performance is one practical approach to rapidly use routine pMTCT cascade data to achieve a systems perspective of pMTCT functioning at the health facility level, and to exploit differences across facilities to identify best practices across health facilities to inform system improvement efforts.


An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time.We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method.In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods.Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade. Scientific Opportunities and Public Needs: Improving Priority Setting and Public Input at the National Institutes of Health, the IOM recommended improved tracking of disease-specific funding and development of a new priority-setting process The National Institutes of Health (NIH) is the largest public funder of biomedical research worldwide A landmark study comparing disease burden to NIH funding levels was published in 1999 To determine whether the NIH has developed processes that better align funding with burden, we assessed the correlation between NIH funding and burden of disease, and compared results with those reported 10 years ago th revision, Clinical Modification (ICD-9)International Classification of Diseases, 9 codes, which were applied to public sources of information on disease burden In a cross-sectional study, we compared measures of US and world disease burden and sociopolitical factors from 2004 to NIH funding levels in 2006. The study design was modeled on methods previously established http://www.nih.gov/news/fundingresearchareas.htm) Amounts of NIH funding for disease categories were obtained directly from the NIH for the year 2006 . These eData denoting disease burden were collected from multiple sources . First, We evaluated five disease burden categories from the GBD: incidence, prevalence, mortality, YLLs, and DALYs To evaluate other estimates of disease burden, we used 2004 US inpatient and outpatient healthcare databases categorized by diagnosis, each of which includes large samples with weights to generate nationally representative estimates  was used for all analyses.Univariate linear regression was first performed to replicate the prior study design In 2006, the total NIH budget was $28.5 billion, with $11.9 billion devoted to the 29 included conditions. Disease funding ranged from $17 million (M) for peptic ulcer disease and otitis media, to $2902 M for AIDS, with a median of $335 M  was also predictive of funding in addition to DALYs (p = 0.006). A model including both variables explained 41% of the variation in NIH funding levels.In multivariable models constrained to require that diseases resulting in no burden of illness receive no NIH funding , but only DALYs were retained in all the multivariable models of both global measures and future predictions. Correlation of funding with disease burden was not improved when data utilizing new NIH accounting methods was used (adjusted R2 = 0.27) compared to prior methods (adjusted R2 = 0.34) applied to 2007 data, the first year for which the new methods were available.To determine if NIH funding might better correlate with world or future disease burden, we performed sensitivity analyses with global measures and future projections (2015 and 2030), all derived from the GBD project  outbreak in 2002, and this may have augmented support for pneumonia-related research Lack of improvement in alignment between funding and disease burden may not indicate neglect of the 1998 IOM recommendations by the NIH; there are several other possible explanations. First, basic science research has consistently accounted for 55% of NIH spending and it is difficult to credit specific disease for much of this research, contributing uncertainty to the analysis and reducing correlations between funding levels and disease burden. Second, NIH funds committed at the time of the 1998 IOM publication could not be redistributed until their associated projects were completed, sometimes five or more years later; as a result, reallocations would be delayed for several years. Third, the distribution of funding among NIH Institutes is determined by Congress and incorporates input from NIH itself, scientists, health care providers, and special interest groups. Thus, fiscal and political constraints likely additionally tempered the NIH's ability to implement the IOM recommendations. Finally, without regard to overall disease funding alignment, substantial financing  was invested in the creation of three new centers  The NIH has recently taken steps to integrate more effectively the IOM priority-setting criteria. In 2007, the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) was established for the purposes of identifying scientific opportunities, public health challenges, and scientific knowledge gaps, and to improve portfolio analysis and priority-setting Our study has several limitations. First, the accounting of disease funding in 2006 by NIH is not standardized nor is the reliability known Overall, funding levels today are less well aligned with DALYs compared to 10 years ago, suggesting that the IOM's 1998 priority-setting recommendations have not been implemented effectively. Accounting for other measures of disease burden did not substantially improve alignment. As a recipient of substantial governmental support, clear articulation of the rationale for NIH spending may be expected by Congress and the public, and a lack of clear alignment with measures of public burden could encourage special interests to further erode the scientific independence of NIH or to raise questions about its management. The use of more consistent accounting methods for disease funding, more comprehensive measures of burden and future risk that include impact on health and expenditures, and the timely dissemination of benchmarks on the alignment of disease burden to funding could help to make NIH funding priorities more rationale and transparent.Table S1Additional Measures of Disease Burden for 29 Conditions.(DOC)Click here for additional data file.Table S2Public Interest and Other Measures for 29 Conditions.(DOC)Click here for additional data file.Table S3World and Future Disability-Adjusted Life-Years as Predictors of NIH Disease-Specific Funding in Fiscal Year 2006.(DOC)Click here for additional data file.


This review introduces and discusses data regarding fundamental and applied investigations in mammalian epigenomics and gut microbiota received over the last 10 years. Analysis of these data enabled us first to come to the conclusion that the multiple low-molecular-weight substances of indigenous gut microbiota origin should be considered one of the main endogenous factors actively participating in epigenomic mechanisms that are responsible for the mammalian genome reprograming and post-translated modifications. Gut microecological imbalance caused by various biogenic and abiogenic agents and factors can produce different epigenetic abnormalities and the onset and progression of metabolic diseases associated. The authors substantiate the necessity to create an international project ‘Human Gut Microbiota and Epigenomics’ that facilitates interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics, and metabolomics investigations as well as in disease prevention and treatment. Some priority scientific and applied directions in the current omic technologies coupled with gnotobiological approaches are suggested that can open a new era in characterizing the role of the symbiotic microbiota small metabolic and signal molecules in the host epigenomics. Although the discussed subject is only at an early stage its validation can open novel approaches in drug discovery studies. For many decades, it has been thought that health and diseases are predominantly driven by acquired genetic changes. Now, it is becoming clear that any phenotype is the result of complex interactions between genotype, epigenome, and environment. Epigenetics focuses on processes that regulate how and when certain genes are turned on and turned off, while epigenomics analyzes epigenetic changes across many genes in a cell or entire organism. In the recent years epigenetics is considered to be at the epicenter of modern medicine because it helps to explain the relationship between individual genotype and the environment during all stages of living beings and perturbations in epigenetic mechanisms can result in various health disturbances –3. EpigeEpstein–Barr virus, hepatitis viruses B and C, Human papilloma virus, polyomaviruses, Streptococcus bovis, Chlamydia pneumoniae, Campylobacter rectus, Helicobacter pylori, and so on) can contribute to the host epigenetic changes resulting in the onset and progression of some metabolic connected diseases, especially in malignancies  and/or cofactors  produced by indigenous intestinal microbiota , 39, 40.Chromatin remodeling has also been linked with the levels of total caloric intake. Energy sensing takes place, in part via the reduced ratio of NADH (nicotinamide adenine dinucleotide) to NAD+ (nicotinamide adenine nucleotide). An NAD + dependent histone deacetylase (sirtuin) appears to be a key modifier of chromatin structure. Acetylation and deacetylation of chromosomal histone proteins alter their interaction causing changes in gene expression regulation. The main donor of acetyl groups for formation of acetyl-CoA that participates in epigenomic acetylation reactions is gut microbiota. Bacteria/eukaryotes share a common pathway for coenzyme A (CoA) biosynthesis from pantothenate (vitamin B5), cysteine, and β-alanine. These essential cofactors are found in most foods in small quantities and are also generated by endogenously and/or by various gut microorganisms. Deficiencies in these nutrients of dietary or microbial origin impair synthesis of acetyl-CoA, NADH and NAD, resulting in disorders of epigenomic acetylation machine that is responsible for chromatin remodeling and post-translation modification of proteins , 23, 43.Some LMW molecules of microbial origin can directly or indirectly activate or inhibit epigenomic regulation through interference to activity of enzymes , which are participants in epigenomic reprograming and/or posttranslation modification of histone and other proteins. As an example, short-chain fatty acids are normally produced by gut microflora, and related products have been approved for human use , 23, 43.During microbial metabolism of cruciferous vegetables or garlic a corresponding number of sulforaphane cysteine/sulforaphane N-acetyl-cysteine and allyl mercaptan/diallyl disulfide are formed that can inhibit the activity of histone deacethyltransferases enzymes . SearchiA vast majority of reports on cross talk between bacteria and epithelial cells have focused on single bacterial strains. But in real life mammalian gut bacteria have never acted on the host cells in isolation, and about 1000 microbial phylotypes and tens of thousands of phylogenetic different bacterial strains in the adult human colon are engaged in constant cross talk with intestinal epithelial cells . This faMultiple LMW metabolites and signal molecules produced by indigenous gut and vaginal microbiota of pregnant women can penetrate via placenta into fetus, resulting in permanent effects of its development programing, cognitive function, metabolism, and body composition in the natal and postnatal periods of life through epigenomic activation or suppression of gene expression, or turning genes ‘on’ or ‘off ’. Information presented above has permitted to suppose that significant alterations in maternal indigenous microbiota may induce long-term metabolic consequences in offspring as a result of disorders of development programing. Thus, imbalance in the mother indigenous gut microbiota may affect adult health and life span as a result of epigenetic variations that may be established during embryonic and fetal development because of consequence of incomplete work of epigenetic machines. Increased supplementation of pregnant women with corresponding diet or microbial origin bioactives   and/or rThus, according to my opinion, diet nutrients and LMW molecules of indigenous microbiota with different metabolic and signal activity can be considered to be correspondingly the most significant exogenous and endogenous environmental determinants, that if not the key determinants, affect gene expression in the host metagenome and post-translation modification of gene products via various epigenetic biochemical mechanisms. These observations can become the basis for development of novel approaches in designing new medicines and diagnostic tests for different pathological syndromes having epigenomic components.www.neb.com/nebe4comm/tech_reference/epigenetics/epigenetics.asp; www.epi.grants.cancer.gov/epigen.html]. To help coordinate efforts, resources, and funding, the authors consider that it is necessary to fund the International Project ‘Human Gut Microbiota and Epigenomics ’. The goals of this project will be to facilitate interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics, as well as disease prevention and treatment. The main aim of such investigations is to establish the profile of microbial LMW substances that characterize the role of human indigenous microbiota in the epigenomic regulation of genome and microbiome activity and protein post-translation modification. The mid term goal is to provide metabolic databases that could be used for selection of microbe-associated biologically active LMW molecules participating in the epigenomic processes. Such small bioactive molecules, either extracted from indigenous (probiotic) microorganisms or their cultural fluids, or synthesized by biochemists, may be later used for activation or inhibition of specific signaling pathways/ enzymatic activities connected with epigenomic regulation effects. Humans are not good experimental subjects because every individual has a unique metogenoepigenotype and it is difficult to control for environmental influences. Therefore, the realization of any Epigenome Projects compulsorily requires active involvement of various gnotobiological models. Advances in the current omic-technologies, coupled with gnotobiological approaches, open a new era in characterizing the role of the symbiotic microbiota in the host epigenomics and have far-reaching implications in the conception relevant to human health and metabolic diseases. Understanding how small molecules of microbial origin interact with the epigenome will permit to design a new generation of epigenetic drugs for curing complex diseases such as cancer and metabolic syndrome-associated diseases.To date several large consortiums or initiatives have been found for investigation in the field of Human being Epigenome: The Human Epigenome Project in Europe; The Alliance for the Human Epigenome and Disease (AHEAD) formed by the American Association for Cancer Research Epigenome Task Force and the European Union Network of Excellence Scientific Advisory Board. In January 2008, The United States National Institute of Health announced that it would invest more than $190 million for the next five years in epigenomics biomedical research [


Translating policies about sustainable development as a social process and sustainability outcomes into the real world of social–ecological systems involves several challenges. Hence, research policies advocate improved innovative problem-solving capacity. One approach is transdisciplinary research that integrates research disciplines, as well as researchers and practitioners. Drawing upon 14 experiences of problem-solving, we used group modeling to map perceived barriers and bridges for researchers’ and practitioners’ joint knowledge production and learning towards transdisciplinary research. The analysis indicated that the transdisciplinary research process is influenced by (1) the amount of traditional disciplinary formal and informal control, (2) adaptation of project applications to fill the transdisciplinary research agenda, (3) stakeholder participation, and (4) functional team building/development based on self-reflection and experienced leadership. Focusing on implementation of green infrastructure policy as a common denominator for the delivery of ecosystem services and human well-being, we discuss how to diagnose social–ecological systems, and use knowledge production and collaborative learning as treatments.The online version of this article (doi:10.1007/s13280-012-0372-4) contains supplementary material, which is available to authorized users. Historically, research policy has swung between a strong sector-focus on solving pre-defined problems and basic research with full academic freedom. Partly as a response to increased awareness of the complexity induced by interactions between human and natural systems at multiple scales, research policy in the European Union (EU) has evolved into research and innovation policies, where utilization of knowledge, implementation, and commercialization are emphasized Anon. . IncreasResearch and innovation are thus at the top of the EU’s agenda for growth and jobs, and Member States have been encouraged to yearly invest 3 % of their Gross Domestic Product in research and development by 2020. The central role of research was recognized by the Lisbon European Council of 2000 Anon. , which eHowever, economic growth and increased competition have historically often resulted in negative impact on the environment Marsh . Still, The societal process of sustainable development (SD) towards sustainability on the ground as defined in policies, requires place and area-based solutions that integrate social and ecological systems in spaces and places  increase collaboration among academic and non-academic actors to facilitate learning and sharing of knowledge and experience  methodology was used to map and analyze major system connections, important feedbacks and system structures affecting researchers’ and practitioners’ ability to become involved with and be successful in transdisciplinary research. A major advantage of the CLD notation is that it uses a common unambiguous language for describing relationships between components within a system, thus clearly communicating the construction of the system thereby facilitating peer review and quality control of the proposed system. The model development process is collaborative and dialectic, that is characterized by successive cycles of suggestions for important systems relationships, critical assessment and critique within the larger group and subsequent redevelopment and improvement. The outcome is a jointly developed, tested and accepted model, which is based on agreement of causal effects between components. This process necessitates all participants to be actively involved, carefully argumentative, and good listeners to others’ arguments and counter arguments. As a language, the CLD method is easily learned and it requires no advanced mathematical knowledge or specialized educational background , social, and human systems . In a new, bio-based and customer-driven European economy, forestry is expected to make significant societal contributions. However, the national rural research strategy Below is the link to the electronic supplementary material.


Delusional-like experiences (DLE) are prevalent in the community. Recent community based studies have found that DLE are more common in those with depression and anxiety disorders, and in those with subclinical symptoms of depression and anxiety. Chronic physical disorders are associated with comorbid depression and anxiety; however, there is a lack of evidence about the association of DLE with common physical conditions. The aim of this study was to explore associations between the common physical disorders and DLE using a large population sample.Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007, a national household survey of 8841 residents aged between 16 and 85 years. The presence of DLE, selected common physical disorders and symptoms were assessed using a modified World Mental Health Composite International Diagnostic Interview (CIDI) schedule. We examined the relationship between DLE, and physical health-related variables using logistic regression, with adjustments for potential confounding factors.Of the 8771, 776 (8.4%) subjects positively endorsed one or more DLE. Of the six physical disorders examined, only diabetes and arthritis were significantly associated with the endorsement of DLE. Of the seven broad physical symptoms explored, only hearing problems were consistently associated with DLE.Delusional-like experiences are common in the Australian community, and are associated with selected chronic physical disorders and with impaired hearing. The direction of causality between these variables warrants closer research scrutiny. Several large community-based surveys have confirmed that many otherwise-well individuals report isolated delusional-like experiences (DLE) It is well recognized that poor general physical health is associated with increased psychological distress and comorbid mental health disorders Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007 (NSMHWB). Details of the survey methodology have been published elsewhere A modified version of the World Mental Health Survey Initiative of the Composite International Diagnostic Interview (WMH-CIDI 3.0) was used to generate DSM-IV lifetime diagnoses of depressive and anxiety disorders, alcohol and other drug abuse disorders Also in keeping with our previous analyses The WMH-CIDI instrument includes two checklists related to the presence of physical disorders and impairments: (a) the National Health Priority Area (NHPA) physical illnesses reference group. Based on previous research of factors associated with DLE post-hoc analysis, we adjusted the main results for education, socio-economic status (‘employment status’ as a proxy variable), and any traumatic events in life as there are well-known associations between physical health and socio-demographic status, and DLE and trauma For the main analyses, we examined the association between DLE (i.e. at least one of the G items was endorsed), and physical illnesses and symptoms using logistic regression where the first category  was used as the Surveylogisticsurveyfreq’ were used.Data were weighted to account for differential probability of selection and to adjust for over- or undersampling of population subgroups Of the 8,771 subjects included in the study, 776 (8.4%) positively endorsed one or more DLE screen items, and 295 (3.0%) endorsed one or more probe items. There was no significant sex difference in endorsing delusional-like experiences . The prevalence of the common physical conditions is shown in The relationship between the selected physical illnesses and DLE as assessed by Screen items are shown in Concerning physical symptoms, the most prevalent symptom was hearing problem (about 9%), while about 6% reported sight problems and restricted physical activity see . Table 3post-hoc analysis where further adjustment was considered with education, socio-economic status and trauma variables (data not shown).In a planned sensitivity analysis where we restricted the DLE screen items to Q1 and Q3 only, the results remained essentially unchanged (data not shown). The results also remained unchanged in the Individuals who report physical disorders including arthritis, gout or rheumatism, and diabetes or high blood sugar were more likely to endorse DLEs compared to those who were otherwise healthy, and this relationship persisted when we adjusted for the presence of common mental conditions such as anxiety disorder or depression. Individuals with arthritis have high scores for pain, physical immobility, impaired sleep and depression With respect to physical impairments, our study found that individuals with sensory impairments but not other physical impairments were more likely to endorse DLE screen items compared to those who did not have these problems. This is congruent with the report that the hearing impairment is associated with an increased risk of psychotic symptoms in both old In our study certain physical disorders and selected symptoms are independently associated with DLE regardless of a range of confounding factors including CIDI diagnoses of depressive and anxiety disorders, alcohol and drug abuse and/or dependence, trauma, socio-demographic variables such as migrant status, marital status, employment, or educational status, and family history of psychosis/schizophrenia. This analysis suggests that the association between physical illness and symptoms is not mediated by the presence of these risk factors.The study has several limitations that merit caution in interpreting the results. The study is cross-sectional; therefore, we cannot comment on the direction of causality. Our results indicate that those who have physical illnesses such as arthritis, diabetes, and those who have physical symptoms such as sight and hearing impairment are more likely to endorse DLE. While we cannot exclude the possibility, it seems less likely that pre-existing DLE might subsequently lead to the onset of co-morbid physical conditions such as arthritis and sensory motor impairment . While individuals with schizophrenia are at increased risk of a range of co-morbid physical conditions related to life style and medication Our study provides evidence that arthritis, diabetes and hearing impairment are associated with delusional-like experiences in the general population. Interest is steadily growing in understanding the clinical utility of DLEs for identification of individuals at greater risk of mental disorders such as anxiety, depression and psychotic disorders. Our study suggests that pathways related to physical health may also contribute to the presence of DLE, perhaps via associated general psychological distress Table S1CIDI Screen and Probes items for Psychosis .(DOCX)Click here for additional data file.


The finding that successful antiretroviral therapy (ART) can almost eliminate the risk of heterosexual HIV transmission is the scientific breakthrough of 2011 according to Science Magazine. This potential of ART has generated novel approaches to prevention including “Test and Treat” (T&T). Our qualitative study, drawing on the perspectives of French HIV experts, aims to better understand if, and how, a T&T approach might be applied in France and to generally learn more about concerns raised by prevention with early ART.In 2011, 19 French HIV experts participated in a semi-structured interview on implementing T&T in France. Expertise was typically defined on the basis of contribution to the 2010 French ART guidelines (Rapport Yeni 2010). Participants’ HIV expertise included clinical care, epidemiology, virology, and community activism. Interviews lasted an hour, on average, and explored opinions on T&T, who, how and whether to test and treat, and what public health discourses and evaluations should accompany it. Analyses of interview content pertaining to who or whether to treat early for prevention are presented here. A content analysis of the transcribed interviews was supported by the software Atlas.ti version 5.2.The decision to treat earlier than current guidelines recommend (CD4 >500) was generally associated with uncertainties and involved weighing the risks and benefits, whether potential or known, primarily in terms of patient health, the risk of transmission, patient choice, population health and/or cost. Perspectives on each of these aspects varied as did experts' position on treating early for prevention.Despite ART-based HIV prevention’s status as evidence based medicine (EBM), French experts had uncertainties about early preventive treatment of HIV-infection which often translated into a weighing of benefits and risks to varying effect. Our findings suggest fostering a culture of dialogue and debate between care providers, community organizations and recipients of care on the complex considerations of implementing strategies of ART as prevention in France can help translate EBM into improvements in health and new HIV guidelines towards the eradication of HIV.


Particle beam therapy has been rapidly developed in these several decades. Proton and carbon ion beams are most frequently used in particle beam therapy. Proton and carbon ion beam radiotherapy have physical and biological advantage to the conventional photon radiotherapy. Cancers of the skull base, nasal cavity, and paranasal sinus are rare; however these diseases can receive the benefits of particle beam radiotherapy. This paper describes the clinical review of the cancer of the skull base, nasal cavity, and paranasal sinus treated with proton and carbon ion beams, adding some information of feature and future direction of proton and carbon ion beam radiotherapy. Particle beam therapy was first proposed in the 1940s [This paper describes the status and prospects of particle beam therapy for the treatment of cancer of the skull base, nasal cavity, and paranasal sinus, including physical, biological, technical, and financial aspects.The physical, biological, technical, and financial aspects of particle beam therapy differ largely from those of conventional photon RT.Both proton and carbon ion beams have features that are extremely different from those of photons. Accelerated proton and carbon ion beams show an increase in energy deposition with penetration depth up to a sharp maximum followed by rapid decrease at the end of the penetration range; this phenomenon is known as the Bragg peak . The parProton and carbon ion beams lose energy when they penetrate a material. With an increasing atomic mass and electric charge of the ions, the ionization density or linear energy transfer (LET) increases. Proton beams have a higher LET than photons; however, their radiobiological properties do not differ substantially from those of photons. For clinical applications, the absorbed dose is multiplied by a factor of 1.1 to express the biological effective dose in cobalt gray equivalents (GyE). Carbon ion beams have a biological advantage over photon and proton beams. Their biological efficiency increases at the end of the beam's range, whereas it is low along the entrance channel. The local values for relative biological effectiveness (RBE) are approximately 3 for carbon ion RT, but depend on many factors. Because carbon ion beams are high-LET ion beams, they can create clusters of DNA damage that cannot be repaired, they are effective for the treatment of hypoxic cells, they cause fewer variations in radiosensitivity related to the cell cycle, and fractionated irradiation is less likely to lead to the repair of radiation-induced injury.Rotating gantries for proton therapy have been installed in more than half of all proton therapy facilities, especially those facilities that have newly opened in the 21st century. Although carbon ion beams have approximately three times the magnetic rigidity of proton beams and are difficult to deflect, they are still delivered in a fixed manner using horizontal or vertical beam lines. The particle therapy facility at the Heidelberger Ionenstrahl-Therapie Centre, Heidelberg, Germany (HIT) has investigated the use of a rotating gantry for carbon ion beams, but this setup has not yet been realized.Beam delivery has been performed using passive methods with modulators, collimators, and compensators at most facilities. The beam is bended using electromagnets and spread by scattering. A ridge filter alters the width of the Bragg peak, and a range shifter adjusts the beam range. The collimator and bolus regulate the outline and depth of the beam based on the target (the systems vary somewhat among institutions). The advantage of a passive beam delivery system is that the treatment planning for this system is simple and can easily produce a conformal irradiation dose, both laterally and at the correct depth, relative to the target. On the other hand, the main disadvantage is that the area along the entrance path is also unavoidably irradiated, and this area often includes nontarget normal tissue. As an alternative to passive beam delivery, active beam delivery techniques, such as spot scanning or raster scanning, have been developed using narrow pencil beams , 3. PencAlthough particle beam therapy has great physical and biological advantages, only a few facilities throughout the world can perform this treatment, as mentioned above. One of the most important disadvantages of particle beam therapy is the high cost of its technical realization and operation. Large cyclotrons or synchrotrons are needed to accelerate protons and carbon ions to the required energy levels for the treatment of deep-seated tumors. A cost analysis study in Europe calculated the capital costs of proton beam RT to be approximately €60–80 million and that of carbon ion beam RT to be €160 million . The ope18FDG) positron emission tomography imaging can provide important information regarding tumor delineation and activity. The investigation of focal dose escalation to substantially inhomogeneous tumors using 18FDG or other tracers, such as fluorine-18 fluoromisonidazole, that are suited for the detection of hypoxic cells has been performed for head and neck cancers; however, useful clinical evidence has not yet been obtained.Chordoma and chondrosarcoma are the most common skull base tumors to be treated using particle beam therapy –16 Tabl. ChordomMunzenrider reported the long-term follow-up data for 519 patients with chordoma or low-grade chondrosarcoma who were treated with proton beams and photons . The patIn summary, the effectiveness of conventional photon RT is limited in patients with chordomas and chondrosarcomas, and postoperative high-dose proton or carbon ion beam RT exhibits excellent tumor control without late side effects and should be selected as an adequate treatment of choice.In recent years, the Paul Scherrer Institute (PSI) and HIT have started active proton and carbon ion beam radiotherapy for the treatment of chordoma and chondrosarcoma patients. Active beam particle beam therapy is, theoretically, extremely adequate for the treatment of skull base tumors in which the tumor and critical organs, such as the optic nerve and brainstem, are tangled together. HIT has also started a prospective comparative phase study of proton and carbon ion beams for the treatment of chordoma and low- and intermediate-grade chondrosarcoma , 19. The18FDG are useful for treatment planning.Squamous cell carcinoma (SCC), malignant melanoma (MM), and ACC are the most common nasal cavity and paranasal sinus cancers to be treated using particle beam therapy , 20–25 . SurgeryThe National Institute of Radiological Sciences, Chiba, Japan (NIRS) reported a dose escalation study examining carbon ion beam RT for head and neck cancer patients . BecausePrevious studies of nasal cavity and paranasal sinus cancer can be divided into two types according to tumor histology: mainly SCC and non-SCC. In a study examining mainly SCC, the irradiation dose was approximately 60–80 GyE and the OS was 50–90% at 2-3 years after treatment. The OS was 90% and the disease-free survival rate was 77% at 3 years in a study in which 78% of the patients, who had mainly SCC, received a gross resection before undergoing RT using proton beams and photons (60.8–77 GyE) , whereasIn summary, the OS of patients with nasal cavity or paranasal sinus cancer varies widely. The rarity of such tumors makes it difficult to perform large studies and may cause a patient bias at each institute. Consequently, comparisons among studies are also difficult. Further studies involving larger numbers of patients are needed.Particle therapy with protons and carbon ion beams offers physical and biological advantages, compared with conventional photon RT. On the other hand, a complex technique is needed, and the capital and operation costs are relatively high. Particle beam therapy is advantageous for the treatment of tumors such as skull base, nasal cavity, and paranasal sinus cancers, as these tumors are often located close to critical organs. A clinical review has revealed that high-dose irradiation is a feasible and safe treatment. To further improve the applicability of particle beam therapy, future developments in the fields of imaging and radiation technology must be fully integrated into the particle therapy process. For example, most modern treatment planning systems include advanced image registration functions. As imaging technologies improve, intensive irradiation dose planning will become more accurate, and an active beam delivery technique will be able to deliver a focally intensive radiation dose to the tumor while avoiding critical organs in the vicinity. Regarding radiation technology, a rotating gantry of carbon ion beams, which is presently under investigation, will be able to overcome the disadvantage of carbon ion beams and should be capable of excellent treatment effects once it is realized.Some clinical studies have examined the treatment of skull base, nasal cavity, and paranasal sinus cancer patients using particle beam therapy. However, because of the rarity of such tumors, definite conclusions were not obtained. Prospective trials involving a large number of patients are needed to obtain clinical evidence. Moreover, past studies have mainly focused on OS, LC, and side effects. In recent years, photon RT is also technically progressing especially development of intensive modulated radiotherapy (IMRT). To apply particle beam therapy widely, a cost performance analysis comparing conventional RT or IM RT is very important in the future studies.


The home environment is an important influence on the sedentary behaviour and physical activity of children, who have limited independent mobility and spend much of their time at home. This article reviews the current evidence regarding the influence of the home physical environment on the sedentary behaviour and physical activity of children aged 8–14 years. A literature search of peer reviewed articles published between 2005 and 2011 resulted in 38 observational studies  and 11 experimental studies included in the review. The most commonly investigated behavioural outcomes were television watching and moderate to vigorous physical activity. Media equipment in the home and to a lesser extent the bedroom were positively associated with children’s sedentary behaviour. Physical activity equipment and the house and yard were not associated with physical activity, although environmental measures were exclusively self-reported. On the other hand, physical activity equipment was inversely associated with sedentary behaviours in half of studies. Observational studies that investigated the influence of the physical and social environment within the home space, found that the social environment, particularly the role of parents, was important. Experimental studies that changed the home physical environment by introducing a television limiting device successfully decreased television viewing, whereas the influence of introducing an active video game on activity outcomes was inconsistent. Results highlight that the home environment is an important influence on children’s sedentary behaviour and physical activity, about which much is still unknown. While changing or controlling the home physical environment shows promise for reducing screen based sedentary behaviour, further interventions are needed to understand the broader impact of these changes. Future studies should prioritise investigating the influence of the home physical environment, and its interaction with the social environment, on objectively measured sedentary time and home context specific behaviours, ideally including technologies that allow objective measures of the home space. Changes to the environment in recent years have contributed to an increase in sedentary behaviour and a decline in activity . The homSedentary behaviour and PA are part of a movement continuum . PA can Ecological models emphasise individual, social and physical environmental influences on PA and sedentary behaviour ,17-19. CAcross the world, home environments are rapidly changing. House sizes in countries such as Australia and the USA have increased, while block and yard sizes have decreased . In contThus, it is timely to review the influence of the home physical environment on children’s PA and sedentary behaviour. The aims of this review were to: (1) examine the impact of interventions that change the home physical environment on children’s PA and sedentary behaviours; (2) summarise the association between home physical environmental factors and children’s PA and sedentary behaviours; (3) explore the relationship of physical and social environmental factors operating within the home space; and (4) highlight current evidence limitations, measurement issues and future research directions. The time of transition from childhood to adolescence, known as preadolescence, represents a specific stage  and has Medline, Web of Science, PsychInfo and Sportdiscus databases were searched for quantitative studies examining the relationship between the physical home environment and preadolescent children’s sedentary behaviours and PA. Combinations of key words were entered in three levels: children; activity; and home environment Figure . The seaInclusion criteria were: (1) sample of healthy children with mean age of between eight and 14 years (at baseline); and (2) outcome variable of sedentary behaviour or PA, including overall time spent sedentary or in PA, or time spent in specific behaviours that potentially occur within the home, such as television watching, video game play, active play and leisure time PA. While preadolescence has most commonly been defined as nine to 13 years , some stArticles were screened in three phases. One reviewer read the title, then abstract and finally the full text, eliminating articles that did not meet the inclusion criteria at each screening phase. Twenty per cent of articles remaining at abstract level were independently screened by a second reviewer to confirm eligibility. Where ambiguity remained, a conclusion was reached by discussion between reviewers. Reference lists from selected articles and relevant review papers were searched for additional articles meeting inclusion criteria.To identify the best available evidence and provide a guide to quality, each paper was assessed according to National Institute for Health and Clinical Excellence (NICE) quality appraisal checklists . Each arEvidence tables summarising the study population, independent and outcome variables, analysis, results, quality assessment and intervention (where applicable), were constructed separately for observational and intervention studies according to NICE methods . To summThirty-eight observational studies and 11 experimental studies were included in the final review , outdoor/free play (4 studies), average activity level (3 studies), inactivity (3 studies), moderate PA (1 study) and light PA (1 study). Ten studies used accelerometers -74,76,77Measures of the home physical environment included media equipment in the home (25 studies), media equipment in the child’s bedroom (20 studies), PA equipment (14 studies) and the parameters of the house and yard (6 studies). Two studies employed a home environment summary including both PA and media equipment ,77. HomeMedia equipment within the home was positively associated with children’s sedentary behaviours in 10 of 16 studies ,74,75,77PA equipment was positively associated with PA outcomes in four of eleven studies ,63,75,77The majority of observational studies investigating the home physical environment also investigated home social environmental variables. Measures included family rules (19 studies), family social support (14 studies) and family behaviours (10 studies). Significant relationships between the home social environment and sedentary behaviours, and to a lesser extent PA, were evident after adjusting for home physical environmental factors. Some form of family social support was positively associated with sedentary behaviours in six of seven cross-sectional studies -45,49,76In the 15 studies with sedentary outcomes that measured both physical and social environmental variables, 10 found associations with physical and social environmental measures ,51,54-56Experimental studies used one of two strategies to change the home physical environment: either introducing a television limiting device or an active video game (AVG).Five randomised control trials (RCT), ranging in duration from six weeks to 12 months, introduced a television limiting device Table . Four stOf the six experimental studies that introduced an AVG into the home, four were RCTs Table . Two RCTThe purpose of this paper was to review the influence of the home physical environment on children’s PA and sedentary behaviour. Results showed that media equipment was positively associated with screen based sedentary behaviours and PA equipment was unrelated to PA, reinforcing results of earlier reviews. Several previously unreviewed relationships were summarised, highlighting an inverse relationship between PA equipment and sedentary behaviour in half of studies. Interventions that changed the home environment by introducing TV limiting devices reduced TV time. The social environment, in particular parents, played an important role in influencing children’s sedentary behaviour and PA even in the presence of home physical environmental factors. The field is limited by the lack of objective assessment and no investigation of the indoor home space beyond equipment. Additionally, there was a paucity of studies investigating objectively measured sedentary time and home context specific behaviours. This review extends previous knowledge by critically assessing and synthesising evidence from both experimental and observational studies. The paper identifies current evidence gaps and measurement issues, and generates future directions for research on children’s sedentary behaviour and PA within the home space.In the current review, investigation of the size, space and design of the house and yard was limited. Although, previous reviews of correlates of children’s physical activity have not addressed this relationship at all ,15,28,29Observational studies showed a positive relationship between media equipment and children’s screen based sedentary behaviours. This extends the findings of earlier reviews that have located few or no studies investigating this relationship ,14 and cThis review located three studies investigating media equipment and objectively measured sedentary time and, to our knowledge, is the first review to summarise this relationship. Findings on the influence of media equipment in the home were mixed and there was no association between bedroom media equipment and accelerometer measured sedentary time ,73,77. EOverall, our results support previous conclusions of limited evidence for a relationship between PA equipment at home and children’s PA ,28,29. HChanging the home physical environment has the potential to influence children’s sedentary behaviour and PA. This review found interventions that implemented a TV limiting device were successful in decreasing children’s screen based sedentary behaviour. Also, introducing an AVG to the home resulted in positive changes in AVG play, sedentary electronic game play, PA and/or body composition in some studies ,86,87, aThe review reaffirms the important role that parents play in supporting, restricting and normalising children’s sedentary behaviours ,16. In aOther authors have called for behaviour specific measures of the environment and context specific measures of PA and sedentary behaviours in the investigation of environmental influences ,92,93. OStudies of the neighbourhood built environment have used objective measures (audits and Geographic Information Systems (GIS)) as well as perceived measures (self-report) ,94 to asTechnology available within homes is changing rapidly and this also has implications for measurement of home media. For example electronic gaming may now be active or sedentary and portable media devices can be used in different places within the home . HoweverFuture studies on the influence of the home physical environment on children’s sedentary behaviour and PA need to investigate home context specific outcomes. The investigation of objectively measured sedentary time at home is most important . SedentaInvestigation of the home physical environment lacks objective assessment and is limited, except for equipment. Future research on the indoor and outdoor home environment should, where applicable, adopt approaches used to measure the outdoor built environment. For example, GIS can provide objective measures of house and yard size  and audiBoth social and physical environmental factors influence children’s sedentary behaviour and PA, yet how they interact within the home space remains unclear. Parents control many elements of the home physical environment. Future research should explore the relationships between parental behaviour, family rules, equipment and arrangement of the home space, to better understand how sedentary behaviour is influenced by the home environment and to inform the development of interventions.Further intervention studies are highly recommended. We found only two types of interventions that changed the home physical environment. TV limiting devices reduced TV viewing, however, it is unknown which behaviours replace TV viewing and whether this strategy is successful in the longer term. Similarly, introducing an AVG showed promise, but any effects seemed to decay quickly. Interventions are required to determine the longer term effects of introducing TV limiting devices and AVGs on activity levels, and any unintended consequences on other physical activities and sedentary gaming. Other strategies such as changing the location of media equipment within the home, reconfiguring indoor spaces and substituting sedentary behaviours with active alternatives are lacking and should be explored. The key challenge for future research is to find acceptable active alternatives to traditionally sedentary behaviours within the home space.This review included the best available evidence from both observational and intervention studies, identifying a larger number of studies with relevant home physical environmental variables than previous reviews. However, there are some limitations to the process and scope of this review. Firstly, some studies may have been missed due to the nature of the search terms and there may be some publication bias to studies with significant results. Secondly, independent and outcome measures were pooled into categories which were useful for summarising evidence, but did not differentiate between very specific environmental measures. For example, the home media equipment category included presence of a TV, presence of a computer, density of media equipment and number of TVs in the home. Thirdly, the summary of the home social environment in isolation should be interpreted with caution as it was limited to papers that also included home physical environmental factors and only the most common social home environmental factors were investigated. Also, individual factors were not included in the review. Finally, the pre-adolescent age group was identified as particularly relevant for investigation, although we acknowledge that this age group encompasses both children and adolescents as defined in previous reviews, and may limit comparability.This review found that both physical and social environmental factors operating within the home space are important influences on children’s sedentary behaviour and PA. Media equipment is associated with children’s screen based sedentary behaviours. Changing the physical environment shows promise for reducing the sedentary nature of homes, although further interventions are needed to understand the broader impact of changes. Considering the substantial amount of time children spend at home, there has been little investigation of how the physical parameters of the home space may constrain or support children’s sedentary behaviour and PA. Future studies should ideally include objective measures of the home and prioritise investigating environmental influences within the home space on objectively measured sedentary time at home and home context specific behaviours.The authors declare that they have no competing interests.CM contributed to the conceptualisation and design of the manuscript, conducted the literature search, quality assessment of papers and analysis, and drafted the manuscript. GS, SF, RB, & MR contributed to the conceptualisation of the manuscript and verification of papers, and provided critical feedback on the manuscript. All authors read and approved the final manuscript.


As evidence grows about the benefits of policy and environmental changes to support active living and healthy eating, effective tools for implementing change must be developed. Youth advocacy, a successful strategy in the field of tobacco control, should be evaluated for its potential in the field of obesity prevention.San Diego State University collaborated with the San Diego County Childhood Obesity Initiative to evaluate Youth Engagement and Action for Health! (YEAH!), a youth advocacy project to engage youth and adult mentors in advocating for neighborhood improvements in physical activity and healthy eating opportunities. Study objectives included documenting group process and success of groups in engaging in community advocacy with decision makers.In 2011 and 2012, YEAH! group leaders were recruited from the San Diego County Childhood Obesity Initiative’s half-day train-the-trainer seminars for adult leaders. Evaluators collected baseline and postproject survey data from youth participants and adult group leaders and interviewed decision makers.Of the 21 groups formed, 20 completed the evaluation, conducted community assessments, and advocated with decision makers. Various types of decision makers were engaged, including school principals, food service personnel, city council members, and parks and recreation officials. Eleven groups reported change(s) implemented as a result of their advocacy, 4 groups reported changes pending, and 5 groups reported no change as a result of their efforts.Even a brief training session, paired with a practical manual, technical assistance, and commitment of adult leaders and youth may successfully engage decision makers and, ultimately, bring about change. As evidence grows about the benefits of policy and environmental changes to support active living and healthy eating , practitThe success of youth advocacy in reducing youth tobacco use provides useful program and evaluation models . Youth aTheory and practice suggest that youth advocacy for obesity prevention is a promising strategy . Youth aWith a population of more than 3 million, San Diego County is the fifth most populous county in the United States . During In 2011, more than 33% of those aged 12 to 17 years in Southern California were overweight or obese .The San Diego County Childhood Obesity Initiative (COI), a program of the nonprofit Community Health Improvement Partners, is a public–private partnership with the mission of reducing and preventing childhood obesity through policy, systems, and environmental change. The COI is structured on 7 domains: government, health care, school and after-school, early childhood, community, media, and businesses. More than 100 community partners participate. COI is governed by a leadership council, which is co-chaired by 2 private pediatricians and San Diego County’s Public Health Officer .3) and CDHS’s Tobacco Control Section Communities of Excellence planning framework. In addition to implementing YEAH! trainings, COI provides technical assistance to groups implementing YEAH!, including in-person, e-mail, and telephone meetings with group leaders.Youth Engagement and Action for Health! (YEAH!) is a youth advocacy and community-empowerment program that engages local youth and adult mentors in advocating for neighborhood improvements in physical activity opportunities and access to healthy foods. YEAH! empowers youth to assess their environments, prioritize problems based on those assessments, and develop and implement an action plan to advocate with decision makers for changes. The YEAH! curriculum and training for adult leaders grew from the County of San Diego Health and Human Services Agency’s pilot projects and is an outgrowth of the California Department of Health Service’s (CDHS) Network for a Healthy California’s project called Communities of Excellence in Nutrition, Physical Activity and Obesity Prevention  to assess the extent to which groups succeeded in engaging in community advocacy with decision makers and 2) to note preliminary successes in securing policy and environmental change as a result of group efforts. Analysis of data on an additional objective, to understand the effect on youth participating in advocacy, is in process.Biannually, COI holds half-day train-the-trainer seminars for adult leaders of youth groups that have an interest in working on healthy eating or active living community advocacy projects. Groups may form as part of school classes or groups, community organizations, after-school programs, religious organizations, and teen centers. The YEAH! manual, available to trainees and to others on request to COI, includes instructions on recruiting youth, gathering resources, conducting community assessments of modifiable environmental factors that affect health , identifying decision makers, and learning to advocate. Groups choose 1 or more assessments to conduct, and on the basis of assessment data, prioritize problems and develop advocacy plans to address 1 or more issues. Youth typically use the assessments, together with photographs or video, to document potential neighborhood or school environmental problems. On completion of their assessments, youth compile their findings into an advocacy presentation, identify relevant decision makers, and deliver their presentation in person, in writing, or through other modes.www.yeahsandiego.org) made by several groups formed during the evaluation summarizes the YEAH! process.The suggested timeline for YEAH! varies with the complexity of project chosen; the manual suggests 4 to 6 months. All groups are run independently, and group leaders have discretion to determine the duration of the project and the frequency and agenda of meetings. During training, group leaders were encouraged to seek technical assistance from the COI as needed. Technical assistance furnished by COI included locating specialized assessment forms and other materials, identifying outside experts to render advice, assisting with identifying appropriate decision makers, and developing advocacy strategies. A brief video  was funded through a grant from the Robert Wood Johnson Foundation and administered through its Active Living Research Program. The conceptual model  drew on The model recognizes multiple levels of influence leading to outcomes, including predisposing characteristics of participants, extent of participation, external support, and group climate, all taking place in various ecological contexts.To measure influences at multiple levels, evaluators collected qualitative and quantitative data through surveys administered to youth and adult group leaders at baseline and after completion of each group’s project. Using a standardized interview protocol, evaluators also interviewed decision makers to whom YEAH! groups had made advocacy presentations. Decision makers were interviewed between 2 weeks and 6 months after the advocacy presentations . Pre- anAdult group leaders in the evaluation study were recruited through the COI training seminars between January 2011 and November 2012. Group leaders who consented received a $150 cash incentive to spend on group-related costs. Youth members of YEAH! groups were recruited for the evaluation study during their first group meeting. Parent consent forms were available in English and Spanish; all surveys were conducted in English. Youth with signed consent and assent forms were asked to complete a written baseline survey and a postproject survey. Gift cards from Subway or Jamba Juice were given to youth and adults who completed the baseline ($10) and postproject survey ($15). San Diego State University’s institutional review board approved the study.At various times during the 2-year evaluation period, 21 groups were formed, and all consented to participate in the evaluation: 20 groups and 136 young participants completed the baseline surveys. We did not collect baseline data from 1 group because the evaluation team did not learn of the group until it was well under way. We estimate that at least 90% of youth participants participated in the baseline survey. There were 52 adult group leaders for the 21 groups; 47 leaders representing 20 groups completed the baseline surveys; and 44 leaders representing 18 groups completed the postproject surveys. Most of the youth participants were girls (73%), and participants were racially/ethnically diverse: 36% were Hispanic; 23% were non-Hispanic black; and 22% were Asian, Pacific Islander, or Native Hawaiian . LeadersGroups formed in 3 settings: 6 in high schools, 6 in middle schools, and 8 in community centers . Groups Twenty groups engaged in advocacy . Most n. AdvocacThis study presents a theory-based evaluation of advocacy, a novel approach to community youth obesity prevention. The evaluation informed COI’s continuation of YEAH! and may assist other communities considering youth advocacy strategies.The YEAH! groups we studied were generally of relatively short duration, with groups meeting for an average of 9 sessions totaling an average of 19 hours per group during 10 weeks. For some groups, according to qualitative data collected from group leaders after project completion, the duration was constrained by resources and time. The short duration may also reflect a lack of experience in youth advocacy; only 9 groups had leaders experienced in youth advocacy , so manyFourteen groups accessed technical assistance from outside experts, and 12 groups consulted with COI. When evaluators contacted groups mid-project, leaders often explained that their groups had completed assessments but were not clear about the next steps in engaging decision makers. More proactive technical assistance may be indicated so that leaders benefit from guidance about political decision-making structures .Among the 12 groups that met at public high schools or middle schools, almost all met at schools with high rates of free or reduced-price lunches . Groups that met at community centers met at after-school centers for children of Navy personnel (n = 3), affordable housing resident groups (n = 3), a community-based organization for East African young women (n = 1) and a job training program for youth on probation (n = 1). The successful implementation of programs in these settings is notable, particularly given the higher prevalence of childhood obesity in underresourced communities. Several groups were based in high schools as part of health science pipeline programs to educate and encourage youth to pursue health-related careers. This setting provides an opportunity to train a new generation of health professionals to be current and future advocates for policies supporting wellness. Institutionalizing YEAH! groups in any of these settings would leverage leader experience, allow youth to mentor each other, and offer the continuity needed to address issues requiring sustained advocacy.Following completion of the evaluation, COI modified the YEAH! training seminars and manual to incorporate the above-mentioned video, more assessment instruments, expanded resources and advocacy planning information, and case studies of successful groups. In 2013, working through its community domain, COI fielded a request for proposals to youth-serving organizations interested in developing YEAH! groups. COI will provide a stipend of $800 to each of the 4 groups selected to participate, as well as technical assistance from a COI advisor who trains leaders, offers individual consultations, and coordinates networking meetings of active group leaders. COI continues to seek funding for the YEAH! coordinator, and future plans are to institutionalize YEAH! in youth-serving organizations such as schools with health-science programs.Key elements of the YEAH! program included 1) close partnerships with organizations serving youth, 2) committed adult leaders trained in the importance of policy and environmental change, and 3) ongoing support to adult leaders from experts with the skills to identify decision makers and facilitate advocacy connections. A community initiative like COI, with existing community partnerships, as well as experienced staff trained in local political process and policy and environmental approaches to obesity issues, was an efficient means to provide the infrastructure and continuity to support the program.We are currently analyzing short-term positive changes among the participating youth based on pre- and post-survey data . Long-teAt the outset of the evaluation, it was unclear if a half-day YEAH! leader training seminar would be adequate to provide skills and information to leaders to engage groups of youth. This evaluation provides evidence that the YEAH! model of providing a brief training, paired with a practical manual and ongoing support for adult mentors, was successful in engaging youth to conduct assessments and advocacy with decision makers in a variety of school and community settings, including groups located in underresourced schools and communities. Ongoing technical support to leaders was important in bridging the process between initial neighborhood assessment and final advocacy with decision makers. As the field accumulates evidence about which policy and environmental changes will best support physical activity and nutrition, it should continue to explore how communities can effectively implement these changes. Next steps in exploring youth advocacy as a policy-change strategy should include exploration of the extent and maintenance of changes secured through advocacy, the potential for institutionalization of youth advocacy in youth-serving organizations, and long-term effects of participation on youth and adult participants.