Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma

T-cell non-Hodgkin's lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin's lymphoma to identify mutational signatures and associated recurrent gene mutations. Signature 1, indicative of age-related deamination, was prevalent across all T-cell lymphomas, reflecting the derivation of these malignancies from memory T-cells. Adult T-cell leukemia-lymphoma was specifically associated with signature 17, which was found to correlate with the IRF4 K59R mutation that is exclusive to Adult T-cell leukemia-lymphoma. Signature 7, implicating UV exposure was uniquely identified in cutaneous T-cell lymphoma (CTCL), contributing 52% of the mutational burden in mycosis fungoides and 23% in Sezary syndrome. Importantly this UV signature was observed in CD4 + T-cells isolated from the blood of Sezary syndrome patients suggesting extensive re-circulation of these T-cells through skin and blood. Analysis of non-Hodgkin's T-cell lymphoma cases submitted to the national 100,000 WGS project confirmed that signature 7 was only identified in CTCL strongly implicating UV radiation in the pathogenesis of cutaneous T-cell lymphoma

Study protocol: can a school gardening intervention improve children's diets?

BACKGROUND: The current academic literature suggests there is a potential for using gardening as a tool to improve children's fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children's fruit and vegetable intake. METHOD/DESIGN: Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as "Partner Schools" and the other to receive the less intensive intervention as "Associate Schools". Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention "Associate Schools" or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children's knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school's gardening activities. DISCUSSION: The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children's fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children's diets and school based interventions. TRIAL REGISTRATION: ISRCTN11396528

The Nutrinet-Santé Study: a web-based prospective study on the relationship between nutrition and health and determinants of dietary patterns and nutritional status

<p>Abstract</p> <p>Background</p> <p>Nutrition-related chronic diseases such as cardiovascular diseases and cancer are of multiple origin, and may be due to genetic, biologic, behavioural and environmental factors. In order to detangle the specific role of nutritional factors, very large population sample cohort studies comprising precisely measured dietary intake and all necessary information for accurately assessing potential confounding factors are needed. Widespread use of internet is an opportunity to gradually collect huge amounts of data from a large sample of volunteers that can be automatically verified and processed. The objectives of the NutriNet-Santé study are: 1) to investigate the relationship between nutrition (nutrients, foods, dietary patterns, physical activity), mortality and health outcomes; and 2) to examine the determinants of dietary patterns and nutritional status (sociological, economic, cultural, biological, cognitive, perceptions, preferences, etc.), using a web-based approach.</p> <p>Methods/design</p> <p>Our web-based prospective cohort study is being conducted for a scheduled follow-up of 10 years. Using a dedicated web site, recruitment will be carried out for 5 years so as to register 500 000 volunteers aged ≥ 18 years among whom 60% are expected to be included (having complete baseline data) and followed-up for at least 5 years for 240 000 participants. Questionnaires administered via internet at baseline and each year thereafter will assess socio-demographic and lifestyle characteristics, anthropometry, health status, physical activity and diet. Surveillance of health events will be implemented via questionnaires on hospitalisation and use of medication, and linkage with a national database on vital statistics. Biochemical samples and clinical examination will be collected in a subsample of volunteers.</p> <p>Discussion</p> <p>Self-administered data collection using internet as a complement to collection of biological data will enable identifying nutrition-related risks and protective factors, thereby more clearly elucidating determinants of nutritional status and their interactions. These are necessary steps for further refining nutritional recommendations aimed at improving the health status of populations.</p

Public Health Stops at the School House Door.

In the United States, all children of appropriate age are required to attend school, and many parents send their children to child care. Many school and day care buildings have been found to have environmental health problems that impact children’s health and diminish their ability to learn. No federal agency has the capacity or authority to identify, track, or remediate these problems. A recent meeting, coordinated by Healthy Schools Network, Inc., has developed a set of recommendations to begin to deal with the issue of environmental health problems in schools

Does physical activity counselling enhance the effects of a pedometer-based intervention over the long-term : 12-month findings from the Walking for Wellbeing in the West study

Peer reviewedPublisher PD

Plasma apolipoprotein J as a potential biomarker for Alzheimer\u27s disease: Australian Imaging, Biomarkers and Lifestyle study of aging

Introduction: For early detection of Alzheimer\u27s disease (AD), the field needs biomarkers that can be used to detect disease status with high sensitivity and specificity. Apolipoprotein J (ApoJ, also known as clusterin) has long been associated with AD pathogenesis through various pathways. The aim of this study was to investigate the potential of plasma apoJ as a blood biomarker for AD. Methods: Using the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the present study assayed plasma apoJ levels over baseline and 18 months in 833 individuals. Plasma ApoJ levels were analyzed with respect to clinical classification, age, gender, apolipoprotein E (APOE) ε4 allele status, mini-mental state examination score, plasma amyloid beta (Aβ), neocortical Aβ burden (as measured by Pittsburgh compound B-positron emission tomography), and total adjusted hippocampus volume. Results: ApoJ was significantly higher in both mild cognitive impairment (MCI) and AD groups as compared with healthy controls (HC; P \u3c .0001). ApoJ significantly correlated with both standardized uptake value ratio (SUVR) and hippocampus volume and weakly correlated with the plasma Aβ1-42/Aβ1-40 ratio. Plasma apoJ predicted both MCI and AD from HC with greater than 80% accuracy for AD and greater than 75% accuracy for MCI at both baseline and 18-month time points. Discussion: Mean apoJ levels were significantly higher in both MCI and AD groups. ApoJ was able to differentiate between HC with high SUVR and HC with low SUVR via APOE ε4 allele status, indicating that it may be included in a biomarker panel to identify AD before the onset of clinical symptoms. © 2016 The Authors

The combined effect of smoking tobacco and drinking alcohol on cause-specific mortality: a 30 year cohort study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Smoking and consuming alcohol are both related to increased mortality risk. Their combined effects on cause-specific mortality were investigated in a prospective cohort study.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Participants were 5771 men aged 35-64, recruited during 1970-73 from various workplaces in Scotland. Data were obtained from a questionnaire and a screening examination. Causes of death were all cause, coronary heart disease (CHD), stroke, alcohol-related, respiratory and smoking-related cancer. Participants were divided into nine groups according to their smoking status (never, ex or current) and reported weekly drinking (none, 1-14 units and 15 or more). Cox proportional hazards models were used to obtain relative rates of mortality, adjusted for age and other risk factors.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; In 30 years of follow-up, 3083 men (53.4%) died. Compared with never smokers who did not drink, men who both smoked and drank 15+ units/week had the highest all-cause mortality (relative rate = 2.71 (95% confidence interval 2.31-3.19)). Relative rates for CHD mortality were high for current smokers, with a possible protective effect of some alcohol consumption in never smokers. Stroke mortality increased with both smoking and alcohol consumption. Smoking affected respiratory mortality with little effect of alcohol. Adjusting for a wide range of confounders attenuated the relative rates but the effects of alcohol and smoking still remained. Premature mortality was particularly high in smokers who drank 15 or more units, with a quarter of the men not surviving to age 65. 30% of men with manual occupations both smoked and drank 15+ units/week compared with only 13% with non-manual ones.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Smoking and drinking 15+ units/week was the riskiest behaviour for all causes of death.&lt;/p&gt

The primary care amplification model: taking the best of primary care forward

Background: Primary care internationally is approaching a new paradigm. The change agenda implicit in this threatens to de-stabilise and challenge established general practice and primary care