COLD-PCR Amplification of Bisulfite-Converted DNA Allows the Enrichment and Sequencing of Rare Un-Methylated Genomic Regions

Aberrant hypo-methylation of DNA is evident in a range of human diseases including cancer and diabetes. Development of sensitive assays capable of detecting traces of un-methylated DNA within methylated samples can be useful in several situations. Here we describe a new approach, fast-COLD-MS-PCR, which amplifies preferentially un-methylated DNA sequences. By employing an appropriate denaturation temperature during PCR of bi-sulfite converted DNA, fast-COLD-MS-PCR enriches un-methylated DNA and enables differential melting analysis or bisulfite sequencing. Using methylation on the MGMT gene promoter as a model, it is shown that serial dilutions of controlled methylation samples lead to the reliable sequencing of un-methylated sequences down to 0.05% un-methylated-to-methylated DNA. Screening of clinical glioma tumor and infant blood samples demonstrated that the degree of enrichment of un-methylated over methylated DNA can be modulated by the choice of denaturation temperature, providing a convenient method for analysis of partially methylated DNA or for revealing and sequencing traces of un-methylated DNA. Fast-COLD-MS-PCR can be useful for the detection of loss of methylation/imprinting in cancer, diabetes or diet-related methylation changes

Innovating Pedagogy 2017: Exploring new forms of teaching, learning and assessment, to guide educators and policy makers. Open University Innovation Report 6

This series of reports explores new forms of teaching, learning and assessment for an interactive world, to guide teachers and policy makers in productive innovation. This sixth report proposes ten innovations that are already in currency but have not yet had a profound influence on education. To produce it, a group of academics at the Institute of Educational Technology in The Open University collaborated with researchers from the Learning In a NetworKed Society (LINKS) Israeli Center of Research Excellence (I-CORE). Themes: • Big-data inquiry: thinking with data • Learners making science • Navigating post-truth societies • Immersive learning • Learning with internal values • Student-led analytics • Intergroup empathy • Humanistic knowledge-building communities • Open Textbooks • Spaced Learnin

Recalibrating the White Cube as a hub for social action

A new form of practice is developing in which cultural organisations are transformed from white cubes to hubs for social action and learning. Focus extends from the showing of art to its creation, and the empowerment and agency of communities through enactive learning. In this model the arts organisation acts as a catalyst for collaborative action and enquiry involving academia and a wider ecosystem of communities and stakeholders including the public, artists, digital creative industry, maker spaces and local government. The new model entails embedding of research, innovation and arts practice within the arts organisation itself. We illustrate the approach with examples of projects spanning mental health, physical disability, young people, veterans, children and parents, which have had a real impact on health and well-being of our communities

Recalibrating the White Cube as a hub for social action

A new form of practice is developing in which cultural organisations are transformed from white cubes to hubs for social action and learning. Focus extends from the showing of art to its creation, and the empowerment and agency of communities through enactive learning. In this model the arts organisation acts as a catalyst for collaborative action and enquiry involving academia and a wider ecosystem of communities and stakeholders including the public, artists, digital creative industry, maker spaces and local government. The new model entails embedding of research, innovation and arts practice within the arts organisation itself. We illustrate the approach with examples of projects spanning mental health, physical disability, young people, veterans, children and parents, which have had a real impact on health and well-being of our communities

Effects of environmental impact and nutrition labelling on food purchasing: An experimental online supermarket study

Nutrition labels and ecolabels can support consumers to make healthier and more sustainable choices, and the former is now widespread. But there is no information on the impact of ecolabels in the presence of nutrition labels. The aims of this study were primarily to examine whether (1) ecolabels are effective at promoting sustainable purchasing behaviour if presented alongside nutrition labels; (2) and secondarily, whether nutrition labels are effective at promoting healthier purchasing if presented alongside ecolabels. Participants (N = 2730) visited an experimental online supermarket platform, and were randomised to see products with (1) environmental impact labels only; (2) nutrition (NutriScore) labels only; (3) both environmental and nutrition labels; (4) no labels. Linear regressions compared the mean environmental impact scores (EIS; primary outcome) and health scores of products in participants’ shopping baskets across each condition. Compared to control (no labels) there were significant reductions in the EIS when environmental impact labels were presented: Alone (−1.3, 95%CI: −2.3 to −0.4) or With nutrition labels (−2.0, 95%CI: −2.9 to −1.0), with no evidence of differences in effectiveness between these two conditions. There was no evidence of an impact of nutrition labels on either the EIS or the healthiness of purchases, both when nutrition labels were shown alone and when ecolabels were also present. Environmental impact labels may be effective at encouraging more sustainable purchases alone or when used alongside nutrition labels. This adds to the evidence base on the feasibility and effectiveness of environmental impact labelling as an important measure to change dietary behaviour to improve planetary health

The global and regional costs of healthy and sustainable dietary patterns: a modelling study.

BACKGROUND: Adoption of healthy and sustainable diets could be essential for safe-guarding the Earth's natural resources and reducing diet-related mortality, but their adoption could be hampered if such diets proved to be more expensive and unaffordable for some populations. Therefore, we aimed to estimate the costs of healthy and sustainable diets around the world. METHODS: In this modelling study, we used regionally comparable food prices from the International Comparison Program for 150 countries. We paired those prices with estimates of food demand for different dietary patterns that, in modelling studies, have been associated with reductions in premature mortality and environmental resource demand, including nutritionally balanced flexitarian, pescatarian, vegetarian, and vegan diets. We used estimates of food waste and projections of food demand and prices to specify food system and socioeconomic change scenarios up to 2050. In the full cost accounting, we estimated diet-related health-care costs by pairing a comparative risk assessment of dietary risks with cost-of-illness estimates, and we estimated climate change costs by pairing the diet scenarios with greenhouse gas emission footprints and estimates of the social cost of carbon. FINDINGS: Compared with the cost of current diets, the healthy and sustainable dietary patterns were, depending on the pattern, up to 22-34% lower in cost in upper-middle-income to high-income countries on average (when considering statistical means), but at least 18-29% more expensive in lower-middle-income to low-income countries. Reductions in food waste, a favourable socioeconomic development scenario, and a fuller cost accounting that included the diet-related costs of climate change and health care in the cost of diets increased the affordability of the dietary patterns in our future projections. When these measures were combined, the healthy and sustainable dietary patterns were up to 25-29% lower in cost in low-income to lower-middle-income countries, and up to 37% lower in cost on average, for the year 2050. Variants of vegetarian and vegan dietary patterns were generally most affordable, and pescatarian diets were least affordable. INTERPRETATION: In high-income and upper-middle-income countries, dietary change interventions that incentivise adoption of healthy and sustainable diets can help consumers in those countries reduce costs while, at the same time, contribute to fulfilling national climate change commitments and reduce public health spending. In low-income and lower-middle-income countries, healthy and sustainable diets are substantially less costly than western diets and can also be cost-competitive in the medium-to-long term, subject to beneficial socioeconomic development and reductions in food waste. A fuller accounting of the costs of diets would make healthy and sustainable diets the least costly option in most countries in the future. FUNDING: Global Panel on Agriculture and Food Systems for Nutrition and Wellcome Trust

Evaluating the Benefits of Restricted Grazing to Protect Wet Pasture Soils in Two Dairy Regions of New Zealand

Many dairy farms in the Manawatu and Southland regions of New Zealand have poorly drained soils that are prone to treading damage, an undesirable outcome on grazed pastures during the wetter months of the year. Removing cows to a stand-off pad during wet conditions can reduce damage, but incurs costs. The objective of this study was to evaluate the impact of different levels of restricted grazing (from 0 to 10 hours grazing time/day for lactating cows) on pasture yield, damage and wastage, feed and stand-off expenses, and farm operating profit. A simulated farm from each region was used in a farm systems model. This model simulated pasture-cow-management interactions, using site-specific climate data as inputs for the soil-pasture sub-models. Days to recover previous yield potential for damaged paddocks can vary widely. A sensitivity analysis (40 to 200 days to recover) was conducted to evaluate the effect of this parameter on results. Full protection when there is risk of damage (0 grazing hours/day) appeared to be less profitable compared with some level of grazing, because the advantages of reduced damage were outweighed by the disadvantages of managing infrequently grazed pastures. The differences in operating profit between full protection and some level of grazing became less as the recovery time increased, but for both regions grazing durations of 6-8 hours/day when a risk of damage is present appeared to be a sensible strategy irrespective of recovery time

Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations