Integrated whole transcriptome and DNA methylation analysis identifies gene networks specific to late-onset Alzheimer’s disease

Previous transcriptome studies observed disrupted cellular processes in late-onset Alzheimer\u27s disease (LOAD), yet it is unclear whether these changes are specific to LOAD, or are common to general neurodegeneration. In this study, we address this question by examining transcription in LOAD and comparing it to cognitively normal controls and a cohort of disease controls. Differential transcription was examined using RNA-seq, which allows for the examination of protein coding genes, non-coding RNAs, and splicing. Significant transcription differences specific to LOAD were observed in five genes: C10orf105, DIO2, a lincRNA, RARRES3, and WIF1. These findings were replicated in two independent publicly available microarray data sets. Network analyses, performed on 2,504 genes with moderate transcription differences in LOAD, reveal that these genes aggregate into seven networks. Two networks involved in myelination and innate immune response specifically correlated to LOAD. FRMD4B and ST18, hub genes within the myelination network, were previously implicated in LOAD. Of the five significant genes, WIF1 and RARRES3 are directly implicated in the myelination process; the other three genes are located within the network. LOAD specific changes in DNA methylation were located throughout the genome and substantial changes in methylation were identified within the myelination network. Splicing differences specific to LOAD were observed across the genome and were decreased in all seven networks. DNA methylation had reduced influence on transcription within LOAD in the myelination network when compared to both controls. These results hint at the molecular underpinnings of LOAD and indicate several key processes, genes, and networks specific to the disease

Focus on vulnerable populations and promoting equity in health service utilization ––an analysis of visitor characteristics and service utilization of the Chinese community health service

Background Community health service in China is designed to provide a convenient and affordable primary health service for the city residents, and to promote health equity. Based on data from a large national study of 35 cities across China, we examined the characteristics of the patients and the utilization of community health institutions (CHIs), and assessed the role of community health service in promoting equity in health service utilization for community residents. Methods Multistage sampling method was applied to select 35 cities in China. Four CHIs were randomly chosen in every district of the 35 cities. A total of 88,482 visitors to the selected CHIs were investigated by using intercept survey method at the exit of the CHIs in 2008, 2009, 2010, and 2011. Descriptive analyses were used to analyze the main characteristics (gender, age, and income) of the CHI visitors, and the results were compared with that from the National Health Services Survey (NHSS, including CHIs and higher levels of hospitals). We also analyzed the service utilization and the satisfactions of the CHI visitors. Results The proportions of the children (2.4%) and the elderly (about 22.7%) were lower in our survey than those in NHSS (9.8% and 38.8% respectively). The proportion of the low-income group (26.4%) was apparently higher than that in NHSS (12.5%). The children group had the lowest satisfaction with the CHIs than other age groups. The satisfaction of the low-income visitors was slightly higher than that of the higher-income visitors. The utilization rate of public health services was low in CHIs. Conclusions The CHIs in China appears to fulfill the public health target of uptake by vulnerable populations, and may play an important role in promoting equity in health service utilization. However, services for children and the elderly should be strengthened

Internet-based medical education: a realist review of what works, for whom and in what circumstances

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Determinants of anthropometric measurement use amongst dieticians

Background: Nutritional assessment, including the measurement and interpretation of anthropometric data, is a pivotal part of the dietitian’s role. However, the extent to which dietitians use anthropometry in their day-to-day activities is poorly documented. Anecdotal evidence suggests that this is below ideal levels. Attitudes and perceived barriers towards the use of anthropometry may further differ by work setting and patient group (e.g. between acute and community-based dietitians). In order to evaluate factors influencing the use of anthropometry amongst dietitians, sensitive, validated tools are needed. Visual analogue scales (VAS) are easily used and interpreted, but have not been validated for assessing confidence levels, in particular when taking body measurements. Aims: This study investigated the use of, and barriers/attitudes towards taking anthropometric measurements amongst dietitians using a cross-sectional survey. For this, a new type of confidence scale (VAS-based) was validated against two other commonly used scales (the Likert and the general-labelled magnitude scale, gLMS). Design and procedure: A pre-piloted questionnaire including confidence scales and attitudinal scales was sent to all NHS dietitians in the North West of England between March-April 2010. The pilot sample (n=32) rated their perceived confidence at taking various anthropometric measures using VAS, Likert and gLMS scales on 2 separate occasions, with scale order randomised. Results: ANOVA and Bland-Altman plot tests indicated VAS to be as sensitive and as reproducible as Likert; VAS also had greater level of agreement with Likert than gLMS, therefore VAS were chosen for the final questionnaire. Of the 397 questionnaires posted, 213 (54%) were returned. Highest confidence ratings were for BMI, height and weight, and lowest for BodPod and head circumference measurements. Average confidence scores across all measurements were lower for community dietitians compared with acute dietitians (mean + SEM scores for community: 54.21 + 14.78 mm; vs. acute: 60.27 + 12.11 mm; p<0.05). The majority of anthropometric measures were reported to be taken on an infrequent basis (‘Never’/’Less than monthly’). Height, weight and BMI were the most commonly used. Significantly more acute than community dietitians used ‘estimated’ (50% vs. 11.3%) and ‘recalled’ weight (50% vs. 11.4%) on a daily basis. The most common barriers against taking measurements were ‘Not appropriate for patient’, ‘Lack of equipment’ and ‘Time/work load constraints’. Significantly more acute responders reported ‘Time’ (81.4%, α=0.003) and ‘Confidence’ (75.5%, α=0.05) to be barriers to anthropometry use. Beyond half of the sample (61%) would attend future training, primarily to increase confidence and competency. Conclusions: Regardless of the importance/reported benefits of anthropometry, it is performed to a very limited degree by dietitians in the North West and is often limited to estimates, BMI, heights and weights. There are numerous barriers to anthropometry use for acute and community dietitians, namely time, equipment and confidence. It may therefore be unrealistic to expect many anthropometric measures to be taken and training should be adapted to reflect the reality of practice. This study also supports the use of VAS scales when assessing dietitians’ confidence at taking anthropometric measurements as a sensitive and reliable tool compared to the more widely used, however less sensitive, Likert scales

The dissemination and implementation of national asthma guidelines in south africa: the use of outcome mapping

Asthma is an important chronic inflammatory disorder with significant morbidity and mortality in South Africa. The development of national asthma guidelines by the South African Thoracic Society and National Asthma Education Programme has been one approach to try and improve the quality of care. The impact of previous guidelines has been limited and therefore it is hoped that the newly revised 2007 guidelines will have a more effective approach to dissemination, implementation and evaluation. Outcome mapping (OM) is one approach to integrated planning, monitoring and evaluation of projects that intend to contribute to change in complex systems. It has a structured, systematic and logical approach that focuses on changes in behaviour, actions or relationships in the people or organizations that the project is working with. OM has three stages - intentional design, outcome/performance monitoring and evaluation - which are described in this article and illustrated with reference to the Asthma Guideline Implementation Project (AGIP). In the intentional design stage the AGIP created a vision and mission statement to guide the project and then identified seven boundary partners. For each boundary partner the AGIP defined the project's outcome challenge and a series of progress markers to monitor achievement of the outcome. Following this the AGIP conceptualized the strategies and organizational practices that will be engaged with to realize the outcomes. In the monitoring stage the AGIP will regularly document and reflect on the progress markers, strategies and organizational practices using pre-determined structured journals. In the evaluation stage there is the opportunity to plan the evaluation of key aspects of the project in more depth. In the AGIP project the team engaged with the development of a doctoral research project to evaluate the process of implementation in private and public primary care settings in the Cape Town metropole. This article describes the methodology of Outcome Mapping and illustrates this in relation to the Asthma Guidelines Implementation Project. The methodology has the potential to be applied in many other development projects and is also congruent with action research. It is hoped that the readers will find this approach useful in their own settings

Evaluation of a school-based nutrition and physical activity programme for Grade 4 learners in the Western Cape province

Objective: This study aimed to evaluate the effectiveness of the Making the Difference programme (MTDP), an education-and activity-based intervention for Grade 4 learners at primary schools in the Western Cape. Design: This was a cross-sectional, post-intervention survey of an existing programme, using control schools as a comparator. Setting and subjects: The study involved Western Cape primary schools in the 2009 school year. Schools were randomly sampled from two regions. Four intervention (active in the MTDP) and five control (non-participating) schools (n = 325 learners) were selected. Outcome measures: The following outcome measures were assessed using an administered questionnaire to learners: learners' knowledge of, attitudes towards, and behaviour in relation to nutrition and physical activity. Results: A small but significant improvement (eating vegetables and taking lunch boxes to school) was demonstrated with regard to self-reported behaviour in relation to nutrition in the intervention group. However, this behaviour was not explained by differences in barriers to healthy eating, self-efficacy or knowledge, which were not different between the groups, or by perceived social support, which was actually significantly increased in the control group. Groups displayed no differences in physical activity or sedentary behaviour. However, the results showed a significant difference between the groups in terms of a reduction in perceived barriers to physical activity and increased physical activity self-efficacy in the active group. Conclusion: While the MTDP only had a modest effect on the self-reported nutrition and physical activity behaviour of the learners, results regarding lower perceived barriers to physical activity and increased physical activity self-efficacy were promising

A new evaluation of the uncertainty associated with CDIAC estimates of fossil fuel carbon dioxide emission

Three uncertainty assessments associated with the global total of carbon dioxide emitted from fossil fuel use and cement production are presented. Each assessment has its own strengths and weaknesses and none give a full uncertainty assessment of the emission estimates. This approach grew out of the lack of independent measurements at the spatial and temporal scales of interest. Issues of dependent and independent data are considered as well as the temporal and spatial relationships of the data. The result is a multifaceted examination of the uncertainty associated with fossil fuel carbon dioxide emission estimates. The three assessments collectively give a range that spans from 1.0 to 13% (2 σ). Greatly simplifying the assessments give a global fossil fuel carbon dioxide uncertainty value of 8.4% (2 σ). In the largest context presented, the determination of fossil fuel emission uncertainty is important for a better understanding of the global carbon cycle and its implications for the physical, economic and political world

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.Postprint (published version

Multifaceted empathy differences in children and adults with autism

Although empathy impairments have been reported in autistic individuals, there is no clear consensus on how emotional valence influences this multidimensional process. In this study, we use the Multifaceted Empathy Test for juveniles (MET-J) to interrogate emotional and cognitive empathy in 184 participants (ages 8–59 years, 83 autistic) under the robust Bayesian inference framework. Group comparisons demonstrate previously unreported interaction effects between: (1) valence and autism diagnosis in predictions of emotional resonance, and (2) valence and age group in predictions of arousal to images portraying positive and negative facial expressions. These results extend previous studies using the MET by examining differential effects of emotional valence in a large sample of autistic children and adults with average or above-average intelligence. We report impaired cognitive empathy in autism, and subtle differences in emotional empathy characterized by less distinction between emotional resonance to positive vs. negative facial expressions in autism compared to neurotypicals. Reduced emotional differentiation between positive and negative affect in others could be a mechanism for diminished social reciprocity that poses a universal challenge for people with autism. These component- and valence- specific findings are of clinical relevance for the development and implementation of target-specific social interventions in autism