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Using Multivariate Statistics

A report of two cases

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

https://journals.sagepub.com/doi/pdf/10.1016/j.icrp.2012.02.001

ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs – Threshold Doses for Tissue Reactions in a Radiation Protection Context

GUEST EDITORIAL PART I: ICRP STATEMENT ON TISSUE REACTIONS PART II: EARLY AND LATE EFFECTS OF RADIATION IN NORMAL TISSUES AND ORGANS - THRESHOLD DOSES FOR TISSUE REACTIONS IN A RADIATION PROTECTION CONTEXT ABSTRACT PREFACE EXECUTIVE SUMMARY GLOSSARY 1. INTRODUCTION 1.1. Purpose of report 1.2. Definition and nature of tissue reactions to ionising radiation 1.3. General principles of radiation effects in cells and tissues 1.4. References 2. RESPONSE OF TISSUES AND ORGANS TO RADIATION 2.1. Haematopoietic and immune systems 2.2. Digestive system 2.3. Reproductive system 2.4. Skin 2.5. Cardiovascular and cerebrovascular systems 2.6. Eye 2.7. Respiratory system 2.8. Urinary tract 2.9. Musculoskeletal system 2.10. Endocrine system 2.11. Nervous system 2.12. References 3. MODIFIERS OF NORMAL TISSUE RESPONSE 3.1. Terminology 3.2. Mechanisms of action 3.3. Influence of modifiers on radiation response in tissue 3.4. References 4. THRESHOLD DOSES IN RELATION TO RADIOSENSITIVITY OF ORGANS AND TISSUES 4.1. Introduction 4.2. Haematopoietic and immune systems 4.3. Digestive system 4.4. Reproductive system 4.5. Skin 4.6. Cardiovascular and cerebrovascular systems 4.7. Eye 4.8. Respiratory system 4.9. Urinary tract 4.10. Musculoskeletal system 4.11. Endocrine system 4.12. Nervous system 4.13. Conclusions 4.14. References ANNEX A. SUMMARY OF STUDIES OF EXPOSURE AND OPACITIES OR CATARACTS

ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs -- threshold doses for tissue reactions in a radiation protection context

Here are two books on a topic new to Technometrics: statistical and mathematical demography. The first author of Applied Mathematical Demography wrote the first two editions of this book alone. The second edition was published in 1985. Professor Keyfritz noted in the Preface (p. vii) that at age 90 he had no interest in doing another edition; however, the publisher encouraged him to find a coauthor. The result is an additional focus for the book in the world of biology that makes it much more relevant for the sciences. The book is now part of the publisher’s series on Statistics for Biology and Health. Much of it, of course, focuses on the many aspects of human populations. The new material focuses on mature population models, the particular focus of the new author (see, e.g., Caswell 2000). As one might expect from a book that was originally written in the 1970s, it does not include a lot of information on statistical computing. The new book by Alho and Spencer is focused on putting a better emphasis on statistics in the discipline of demography (Preface, p. vii). It is part of the publisher’s Series in Statistics. The authors are both statisticians, so the focus is on statistics as used for demographic problems. The authors are targeting human applications, so their perspective on science does not extend any further than epidemiology. The book actually strikes a good balance between statistical tools and demographic applications. The authors use the first two chapters to teach statisticians about the concepts of demography. The next four chapters are very similar to the statistics content found in introductory books on survival analysis, such as the recent book by Kleinbaum and Klein (2005), reported by Ziegel (2006). The next three chapters are focused on various aspects of forecasting demographic rates. The book concludes with chapters focusing on three areas of applications: errors in census numbers, financial applications, and small-area estimates.

Univariate Discrete Distributions

Medical exposures form the largest manmade contributor to total ionising radiation exposure of the UK population. In recent years, new technologies have been developed to improve treatment and prog...

The 2019 Bo Lindell Laureate Lecture: On the use of interdisciplinary, stakeholder-driven, radiation protection research in support of medical uses of ionising radiation.

Estimated Radiation Dose to the Operator During Endovascular Aneurysm Repair.

Higher Incidence of Chromosomal Aberrations in Operators Performing a Large Volume of Endovascular Procedures.

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0 Gy to 4 Gy at two different facilities in Germany (PTB) and USA (CINF). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semi-automatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semi-automatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed non-linear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts.

International comparison exercise for biological dosimetry after exposures with neutrons performed at two irradiation facilities as part of the BALANCE project.

Elizabeth A. Ainsbury

Papers

The 2019 Bo Lindell Laureate Lecture: On the use of interdisciplinary, stakeholder-driven, radiation protection research in support of medical uses of ionising radiation.

Estimated Radiation Dose to the Operator During Endovascular Aneurysm Repair.

Higher Incidence of Chromosomal Aberrations in Operators Performing a Large Volume of Endovascular Procedures.

International comparison exercise for biological dosimetry after exposures with neutrons performed at two irradiation facilities as part of the BALANCE project.