The challenge of modelling nitrogen management at the field scale : simulation and sensitivity analysis of N2O fluxes across nine experimental sites using DailyDayCent

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The FAOSTAT database of greenhouse gas emissions from agriculture

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Modelling spatial and inter-annual variations of nitrous oxide emissions from UK cropland and grasslands using DailyDayCent

This work contributes to the Defra funded projects AC0116: ‘Improving the nitrous oxide inventory’, and AC0114: ‘Data Synthesis, Management and Modelling’. Funding for this work was provided by the UK Department for Environment, Food and Rural Affairs (Defra) AC0116 and AC0114, the Department of Agriculture, Environment and Rural Affairs for Northern Ireland, the Scottish Government and the Welsh Government. Rothamsted Research receives strategic funding from the Biotechnology and Biological Sciences Research Council. This study also contributes to the projects: N-Circle (BB/N013484/1), U-GRASS (NE/M016900/1) and GREENHOUSE (NE/K002589/1).Peer reviewedPublisher PD

In utero antihypertensive medication exposure and neonatal outcomes : A data linkage cohort study

We acknowledge the support from the Farr Institute @ Scotland. The Farr Institute @ Scotland is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates), the Wellcome Trust, (MRC grant number MR/K007017/1).Peer reviewedPublisher PD

A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

Background: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects. Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years]) with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5) or 1000 mg (n = 7) of a Maritech® extract formulation per day. The formulation contained Maritech® seaweed extract containing Fucus vesiculosis (85% w/w), Macrocystis pyrifera (10% w/w) and Laminaria japonica (5% w/w) plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT) score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded. Results: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect seen between the two treatments (P≤0.0005) on the average COAT score and each of the four COAT subscales (pain, stiffness, difficulty with physical activity and overall symptom severity) (P≤0.05). The preparation was well tolerated and the few adverse events were unlikely to be related to the study medication. There were no changes in blood parameters measured over the course of the study with the exception of an increase in serum albumin which was not clinically significant. Conclusion: The seaweed extract nutrient complex when taken orally over twelve weeks decreased the symptoms of osteoarthritis in a dose-dependent manner. It was demonstrated to be safe to use over the study period at the doses tested. The efficacy of the preparation now needs to be demonstrated in a phase III randomized controlled trial (RCT). Australian and New Zealand Clinical Trials Register: ACTRN12607000229471

A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex

Background: Isolated fucoidans from brown marine algae have been shown to have a range of immune-modulating effects. This exploratory study aimed to determine whether a seaweed nutrient complex containing a blend of extracts from three different species of brown algae plus nutrients is safe to administer and has biological potential as an immune modulator. The study was undertaken as an open-label combined Phase I and II study. Methods: Participants (n = 10) were randomized to receive the study medication at either a 100 mg (n = 5) or 1000 mg (n = 5) dose over 4 weeks. The primary outcome measurement was in vivo changes in lymphocyte subsets. The secondary outcome measures were ex vivo changes in T-lymphocyte (CD4 and CD8) activation, phagocytosis of granulocytes and monocytes, T helper 1/T helper 2 cytokines, and serum oxygen radical absorbance capacity. Results: The preparation was found to be safe over the 4 weeks at both doses tested. There were no clinically relevant changes to blood measurements of hemopoietic, hepatic, or renal function. Immunomodulatory measurements showed no dose response between the two doses. The combined results from the two doses demonstrated a significant increase in cytotoxic T cell numbers and phagocytic capacity in monocytes, and a significant decrease in levels of the inflammatory cytokine interleukin 6. A separate analysis of the 100 mg dose (n = 5) alone showed a significant linear component over time (P \u3c 0.05) for phagocytosis by both granulocytes and monocytes. Conclusion: The seaweed nutrient complex was safe to use when taken orally over 4 weeks. The preparation was demonstrated to have potential as an immune modulator, and this bioactivity deserves further exploration

Educational and health outcomes of children and adolescents receiving antidepressant medication : Scotland-wide retrospective record linkage cohort study of 766 237 schoolchildren

Funding Health Data Research UK (grant reference number MR/S003800/1). Acknowledgements The study was sponsored by Health Data Research UK (www.hdruk.ac.uk), which is a joint investment led by the Medical Research Council, together with the National Institute for Health Research (England), the Chief Scientist Office (Scotland), Health and Care Research Wales, Health and Social Care Research and Development Division (Public Health Agency, Northern Ireland), the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the British Heart Foundation and Wellcome (grant reference number MR/S003800/1). The sponsor and funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication. This study formed part of a wider PhD thesis undertaken by the lead author within the University of Glasgow and was published in 2017. Certain sections of this paper appear in the thesis, which is accessible and downloadable from the following link: http://theses.gla.ac.uk/8594/1/2017flemingphd.pdf. Author Contributions J.P.P. had the original concept. All authors agreed the study design. D.C. and A.K. provided data and undertook record linkage. M.F. and D.F.M. undertook the statistical analyses. All authors interpreted the results. M.F. and J.P.P. drafted the manuscript and all other authors contributed revisions. All authors reviewed and approved the final version of the manuscript. M.F. is guarantor for the study. Approvals The authors applied for permission to access, link and analyse these data and undertook mandatory training in data protection, IT security and information governance. Therefore, the datasets generated and analysed during the study are not publicly available. The study was approved by the National Health Service Privacy Advisory Committee and covered by a data-processing agreement between Glasgow University and ISD, and a data-sharing agreement between Glasgow University and ScotXed. All data were linked by the Electronic Data Research and Innovation Service (eDRIS), part of NHS National Services Scotland. Ethics The NHS West of Scotland Research Ethics Service confirmed that formal NHS ethics approval was not required, since the study involved anonymized extracts of routinely collected data with an acceptably negligible risk of identification. Conflict of interest: None declaredPeer reviewedPublisher PD

Educational and health outcomes of children and adolescents receiving antiepileptic medication : Scotland-wide record linkage study of 766 244 schoolchildren

Acknowledgements The study was sponsored by Health Data Research UK (www.hdruk.ac.uk) which is a joint investment led by the Medical Research Council, together with the National Institute for Health Research (England), the Chief Scientist Office (Scotland), Health and Care Research Wales, Health and Social Care Research and Development Division (Public Health Agency, Northern Ireland), the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the British Heart Foundation and Wellcome. This study formed part of a wider PhD thesis undertaken by the lead author within the University of Glasgow, which was published in 2017. Therefore, certain sections of this paper appear in the thesis, which is accessible and downloadable from the following link: http://theses.gla.ac.uk/8594/1/2017flemingphd.pdf. Funding The study was sponsored by Health Data Research UK. The sponsor and funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript, or decision to submit the manuscript for publication. Availability of data and materials The authors applied for permission to access, link and analyse these data and undertook mandatory training in data protection, IT security and information governance. Therefore, the datasets generated and analysed during the study are not publicly available.Peer reviewedPublisher PD

Educational and health outcomes of children treated for type 1 diabetes: Scotland-wide record linkage study of 766,047 children

Objective: This study was conducted to determine the association between childhood type 1 diabetes and educational and health outcomes. Research Design and Methods: Record linkage of nine Scotland-wide databases (diabetes register, dispensed prescriptions, maternity records, hospital admissions, death certificates, annual pupil census, school absences/exclusions, school examinations, and unemployment) produced a cohort of 766,047 singleton children born in Scotland who attended Scottish schools between 2009 and 2013. We compared the health and education outcomes of schoolchildren receiving insulin with their peers, adjusting for potential confounders. Results: The 3,330 children (0.47%) treated for type 1 diabetes were more likely to be admitted to the hospital (adjusted hazard ratio [HR] 3.97, 95% CI 3.79–4.16), die (adjusted HR 3.84, 95% CI 1.98–7.43), be absent from school (adjusted incidence rate ratio [IRR] 1.34, 95% CI 1.30–1.39), and have learning difficulties (adjusted odds ratio [OR] 1.19, 95% CI 1.03–1.38). Among children with type 1 diabetes, higher mean HbA1c (particularly HbA1c in the highest quintile) was associated with greater absenteeism (adjusted IRR 1.75, 95% CI 1.56–1.96, P < 0.001), increased school exclusion (adjusted IRR 2.82, 95% CI 1.14–6.98), poorer attainment (adjusted OR 3.52, 95% CI 1.72–7.18), and higher risk of unemployment (adjusted OR 2.01, 95% CI 1.05–3.85). Conclusions: Children with type 1 diabetes fare worse than their peers in respect of education and health outcomes, especially if they have higher mean HbA1c. Interventions are required to minimize school absence and ensure that it does not affect educational attainment