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R Wakeford

Publications and source records attributed to R Wakeford.

At least 19 recordsLinked to original sources
PubMed2003

Risk coefficients for childhood cancer after intrauterine irradiation: a review.

PURPOSE: To review the estimates of the risk of childhood cancer per unit dose of radiation received in utero derived from the largest case-control study of obstetric X-ray examinations and to compare them with the childhood cancer risk coefficients obtained from the cohorts of Japanese atomic bomb survivors irradiated either in utero or as young children. MATERIALS AND METHODS: Data from the Oxford Survey of Childhood Cancers (OSCC) case-control study of foetal exposure to diagnostic X-rays and from the cohort studies of the Japanese survivors of the atomic bombings of Hiroshima and Nagasaki were used, together with associated dose estimates. Excess relative risk and excess absolute risk coefficients were compared, fully taking into consideration the various sources of uncertainty. RESULTS: The excess relative risk coefficient for childhood (< 15 years of age) cancer obtained from the OSCC was around 50 Gy(-1), leading to an excess absolute risk coefficient for incident cases of about 8% Gy(-1). However, the statistical, dosimetry, modelling and other uncertainties associated with these risk estimates are appreciable, and there is reason to believe that these coefficients could be systematic overestimates. When these uncertainties and those associated with the equivalent risk coefficients derived from the Japanese cohort exposed in utero are taken into account, the risk estimates for childhood cancer obtained from these two sources are compatible. These coefficients are consistent with the high relative risk of childhood leukaemia among the Japanese survivors exposed as children. The absence of cases of childhood solid tumours among the Japanese children irradiated after birth in contrast to the significant excesses found in both intrauterine exposure studies might be explained by the cells from which these cancers originate being predominantly sensitive only to exposure in utero. CONCLUSIONS: The consistency of the childhood cancer risk coefficients derived from the Oxford Survey and from the Japanese cohort irradiated in utero supports a causal explanation of the association between childhood cancer and an antenatal X-ray examination found in case-control studies. This implies that doses to the foetus in utero of the order of 10 mSv discernibly increase the risk of childhood cancer. However, uncertainties in risk estimates are such that it is difficult to conclude reliably from these epidemiological data what the level of risk at these low doses might be, beyond the inference that the risk is not zero or has been grossly underestimated.

Adolescent↗
PubMed2002

The use of portfolios for assessment of the competence and performance of doctors in practice.

BACKGROUND: The use of portfolios can potentially provide flexibility in the summative assessment of doctors in practice. An assessment system should reflect and reinforce the active and planned professional development goals of individual doctors. This paper discusses some of the issues involved in developing such a system. RESULTS: To provide a complete picture of an individual doctor's practice, we suggest that a portfolio should encompass: (1) evidence covering all three domains of patient care, personal development and context management; (2) evidence that the person continuously undertakes critical assessment of their own performance, identifies and prioritises areas requiring enhanced performance and takes action to improve them as appropriate; (3) evidence that has been generated by assessments that are acceptably reliable, and (4) evidence which, taken in its entirety, is sufficient, valid, current and authentic. We include a suggested outline of the components of such a portfolio and suggest some criteria to determine the effectiveness of learning cycles. Portfolio reliability and validity requires sufficient evidence on which to base a judgement combined with reliable processes. CONCLUSION: Carefully specified portfolios can contribute to a system that ensures all doctors take an active part in identifying and meeting their own learning needs. Such a system, if properly implemented, would have a greatly beneficial impact on continuous quality improvement for the profession in general.

Clinical Competence↗
PubMed2002

The bystander effect in experimental systems and compatibility with radon-induced lung cancer in humans.

Bystander effects following exposure to alpha-particles have been observed in C3H 10T1/2 cells and in other experimental systems, and imply that linearly extrapolating low-dose risks from high-dose data might materially underestimate risk. The ratio of lung cancer risk among persons exposed to low and high doses of radon daughters is 2.4-4.0, with an upper 95% confidence limit (CL) of about 14. Assuming that the bystander effect observed in the C3H 10T 1/2 data applies to human lung cells in vivo, the epidemiological data imply that the number of neighbouring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% CL of about 7. As a consequence, the bystander effect observed in the C3H 10T1/2 system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans. Other experimental data relating to the bystander effect after alpha-particle exposure are surveyed; some of these data are more compatible with the epidemiological data.

Air Pollutants↗
PubMed2001

Radiation litigation and the nuclear industry--the experience in the United Kingdom.

In the United Kingdom, the Nuclear Installations Act 1965 places a "strict" statutory duty on the operators of nuclear facilities to ensure that any exposure to radiation resulting from operations does not cause injury or damage. A claimant does not have to prove fault to receive compensation under the Act, only causation. The 1965 Act has been fundamental in shaping litigation involving the nuclear industry in the UK. Civil law cases brought under the Act will be heard before a single judge (with no jury or technical assessor) who must present his or her decision in a reasoned judgment. This process leads to a considerable volume of expert evidence being presented to the court and extensive cross-examination of witnesses. The expense and uncertain outcome of cases involving claims by nuclear workers that occupational exposure to radiation had caused the development of cancer has led to employers and trade unions setting up the voluntary Compensation Scheme for Radiation-linked Diseases as an alternative to litigation. This Scheme has worked well and is held up as a model of alternative dispute resolution. However, a few cases concerning personal injury or damage to property have come before the courts when the defendant nuclear operator considered that the claims were technically unjustified and where settlement was not a policy option. As anticipated, these cases were lengthy, complex, and expensive. The radiation doses assessed to have been received by the individuals who were the subject of claims, whether workers or members of the public, have been crucial to the outcome. The technical expertise of health physicists and allied specialists has been vital in establishing defensible estimates of dose, and this contribution can be expected to remain of high importance in radiation litigation in the UK.

History, 20th Century↗
PubMed2001

The bystander effect in C3H 10T cells and radon-induced lung cancer.

Little, M. P. and Wakeford, R. The Bystander Effect in C3H 10T(1/2) Cells and Radon-Induced Lung Cancer. Radiat. Res. 156, 695-699 (2001).Bystander effects, whereby cells that are not directly exposed to radiation exhibit adverse biological effects, have been observed in a number of experimental systems, including C3H 10T(1/2) cells exposed to alpha-particle radiation. The bystander effect implies that risks from exposure to low doses of radiation obtained by linear extrapolation from data for high-dose exposures might be substantial underestimates. The best estimate of the ratio of the lung cancer risk among persons exposed to low (residential) doses of radon daughters to that among persons (underground miners) exposed to high doses of radon daughters is in the range of 2.4-4.0, with an upper 95% confidence limit of about 14. Assuming that the bystander effect observed in the in vitro C3H 10T(1/2) cell system applies to human lung cells in vivo, these epidemiological data imply that the central estimate of the number of neighboring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% confidence limit of about 7. As a consequence, the bystander effect observed in the experimental C3H 10T(1/2) cell system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans.

Alpha Particles↗
PubMed1999

Design and synthesis of thrombin inhibitors: analogues of MD-805 with reduced stereogenicity and improved potency.

Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibitors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3, 3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, P2-FEP, and P1-arginine (45g) had a K(i) of 6 nM (MD-805 K(i) = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

Animals↗
PubMed1998

A review of probability of causation and its use in a compensation scheme for nuclear industry workers in the United Kingdom.

The assumption that any additional exposure to ionizing radiation leads to an increase in the risk of stochastic health effects implies that some cases of these effects will be caused by exposure incurred occupationally. The main health effect expected to arise in the exposed individuals is cancer. Such radiation-induced cancers cannot be distinguished from the far larger number of background cancers, and, therefore, causation must be assessed statistically. The probability of causation methodology has been developed to ascertain the likelihood that a particular cancer may be attributed to a particular prior exposure to radiation. Given the pertinent details of an individual case, a probability of causation value is calculated from the appropriate relative risk obtained from radiation risk models derived from the epidemiological study of exposed populations, although there are many uncertainties inherent in a particular probability of causation calculation. In the United Kingdom, the Compensation Scheme for Radiation-linked Diseases has been created to determine whether those individuals occupationally exposed to radiation in the nuclear industry who have subsequently developed a malignant disease should be compensated. The Scheme is a voluntary arrangement based upon the probability of causation methodology, which incorporates various procedures agreed by employer and employee representatives and their advisers. In a pragmatic approach to compensation, the uncertainties of a specific probability of causation calculation are accommodated through generosity factors which favor the claimant and encourage the use of the Scheme. The Scheme, which was introduced in 1982 and modified in 1987 and 1991 in the light of operational experience and revised risk estimates, has provided a successful alternative to litigation from the point of view of both employer and employee.

Humans↗