Professor John Harrison

Background. Dietary interventions including consumption of flavonoids, plant compounds found in certain foods, may have the ability to improve fatigue. However, to date, no well-designed intervention studies assessing the role of flavonoid consumption for fatigue management in people with MS (pwMS) have been performed. The hypothesis is that the consumption of a flavonoid-rich pure cocoa beverage will reduce fatigue in pwMS. The aim of this study is to determine the feasibility and potential outcome of running a trial to evaluate this hypothesis.
Methods. Using a randomised (1:1) double-blind placebo-controlled feasibility study, 40 men and women (20 in each trial arm) with a recent diagnosis (< 10 years) of relapsing and remitting MS (RRMS) and who are over 18 years of age will be recruited from neurology clinics and throughout the Thames Valley community. During a 6-week nutrition intervention period, participants will consume the cocoa beverage, high flavonoid or low flavonoid content, at breakfast daily. At baseline, demographic factors and disease-related factors will be assessed. Fatigue, activity and quality of life, in addition to other measures, will be taken at three visits (baseline, week 3 and week 6) in a university setting by a researcher blinded to group membership. Feasibility and fidelity will be assessed through recruitment and retention, adherence and a quantitative process evaluation at the end of the trial. We will describe demographic factors (age, gender, level of education) as well as disease-related factors (disease burden scores, length of time diagnosed with MS) and cognitive assessment, depression and quality of life and general physical activity in order to characterise participants and determine possible mediators to identify the processes by which the intervention may bring about change. Feasibility (recruitment, safety, feasibility of implementation of the intervention and evaluation, protocol adherence and data completion) and potential for benefit (estimates of effect size and variability) will be determined to inform future planned studies. Results will be presented using point estimates, 95% confidence intervals and p values. Primary statistical analysis will be on an intention-to-treat basis and will use the complete case data set. Discussion. We propose that a flavonoid-enriched cocoa beverage for the management of fatigue will be well received by participants. Further, if it is implemented early in the disease course of people diagnosed with RRMS, it will improve mobility and functioning by modifying fatigue. Trial registration: Registered with ISRCTN Registry. Trial registration No: ISRCTN69897291; Date April 2016.

Mr Litvinenko died on 23rd November 2006, having been poisoned with polonium-210 on 1st November, with evidence of a previous poisoning attempt during October 2006. Measurements of 210Po in urine samples were made for a large number of people to determine whether they may have been contaminated. In the majority of cases, measured levels were attributable to the presence of 210Po from normal dietary sources. For a small number of cases, elevated levels provided evidence of direct contamination associated with the poisonings. For one individual,
while estimated doses were below thresholds for irreversible organ damage, a notably increased risk of cancer can be inferred. The use of the chelating agent, Unithiol, to increase 210Po excretion in this case was only moderately effective in reducing doses received.

Assessments of risk to a specific population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficients used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the associated risk is important for informing judgments on reliability; a derived uncertainty factor, UF, is an estimate of the 95% probable geometric difference between the best risk estimate and the nominal risk and is a useful tool for making this assessment. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioiodine by members of the public, specifically 1, 10 and 20-year old females from the population of England and Wales. Best estimates of thyroid cancer incidence risk (lifetime attributable risk) are calculated for ingestion or inhalation of 129I and 131I, accounting for uncertainties in biokinetic model and cancer risk model parameter values. These estimates are compared with the equivalent ICRP derived nominal age-, sex- and population-averaged estimates of excess thyroid cancer incidence to obtain UFs. Derived UF values for ingestion or inhalation of 131I for 1 year, 10-year and 20-year olds are around 28, 12 and 6, respectively, when compared with ICRP Publication 103 nominal values, and 9, 7 and 14, respectively, when compared with ICRP Publication 60 values. Broadly similar results were obtained for 129I. The uncertainties on risk estimates are largely determined by uncertainties on risk model parameters rather than uncertainties on biokinetic model parameters. An examination of the sensitivity of the results to the risk models and populations used in the calculations show variations in the central estimates of risk of a factor of around 2–3. It is assumed that the direct proportionality of excess thyroid cancer risk and dose observed at low to moderate acute doses and incorporated in the risk models also applies to very small doses received at very low dose rates; the uncertainty in this assumption is considerable, but largely unquantifiable. The UF values illustrate the need for an informed approach to the use of ICRP dose and risk coefficients.

Mr Litvinenko died on 23 November 2006 after having been poisoned with polonium-210 on 1 November. Measurements of the polonium-210 content of post-mortem tissue samples and samples of urine and blood showed the presence of large amounts of 210Po. Autoradiography of hair samples showed two regions of 210Po activity, providing evidence of an earlier poisoning attempt during October 2006, resulting in absorption to blood of about one-hundredth of that estimated for 1 November. Intake by ingestion on 1 November was estimated to be around 4 GBq, assuming 10% absorption to blood, and the resulting organ doses reached estimated values that were generally in a range from about 20 Gy to over 100 Gy. Comparison with estimates of protracted alpha particle doses required to cause irreversible organ damage supported the conclusion that death was the inevitable consequence of multiple organ failure, with destruction of the haemopoietic bone marrow, as well as damage to kidneys and liver, being important contributors. If the earlier poisoning during October 2006 had not been followed by a second major intake on 1 November, it is possible that the earlier intake of around 40 MBq, with absorption of 4 MBq to blood, might have caused irreversible kidney damage over a prolonged period of months or years, with doses of approaching 3 Gy.