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Mathematical models play an important role in management of outbreaks of acute respiratory infections (ARI). While such models are generally used to study the spread of a solitary virus, in reality multiple viruses co-circulate in the population. These viruses have been studied in detail, including the course of infection and immune defense mechanisms. We developed an agent-based model, called ABM-ARI, assimilating heterogeneous data and theoretical knowledge into a biologically motivated system, that allows to reproduce the seasonal patterns of ARI incidence and simulate interventions. ABM-ARI uses city-specific data to create a synthetic population and to construct realistic contact networks in different activity settings. Characteristics of infection, immune protection and non-specific resistance were varied between individuals to account for the population heterogeneity. For the calibration, we minimised the normalised mean absolute error between simulated and observed epidemic curves. ABM-ARI was built based on the quantitative assessment of features of predominant respiratory viruses and epidemiological characteristics of the population. It provides a good fit to the observed epidemic curves for different age groups and viruses. We also simulated one-week school closures when student absences were at or above 10%, 20% or 30% and found that only 10% and 20% thresholds resulted in a reduction of the incidence. ABM-ARI has a great potential in tackling the challenge of emerging infections by simulating and evaluating the effectiveness of various interventions., (© 2023. The Author(s), under exclusive licence to Society for Mathematical Biology.)

Background: During the COVID-19 pandemic, many countries used lockdowns as a containment measure. While lockdowns successfully contributed to slowing down the contagion, the related mobility restrictions were reportedly associated with an increased risk of major depressive and anxiety disorders. We aimed to quantify the trade-off between the quality-adjusted life years (QALY) gain due to lower COVID-19 incidence as a result of a lockdown and QALY loss due to lockdown-induced mental disorders., Methods: We developed an agent-based model of COVID-19 epidemic and coupled mental disorder development in the population of a large city. We used data sources on the places of living, studying and working, public health and census surveys. Modeling of mental disorders was based on diathesis-stress concept. We quantified mental and physical health burden in terms of QALY taking into account major depressive and anxiety disorder episodes, lethal and non-lethal cases of COVID-19, and immunization., Findings: We evaluated the dynamics of new major depressive disorder (MDD) and anxiety disorder (AD) cases during the period between September 2020 and December 2021 in Moscow, Russia. We found that lockdown imposition increases the daily chances of getting MDD or ADD by a vulnerable person by 16.79% (95% CI [12.36%, 21.23%]). The QALY loss associated with COVID-19-induced and lockdown-induced mental disorders was estimated to be 18.93% (95% CI [16.94%, 19.73%]) of the total QALY loss caused by COVID-19, immunization, and all kinds of mental disorders. For a synthetic "strong" lockdown, it had been shown that QALY loss is minimized when about 70% of the population are isolated., Interpretation: The burden associated with mental disorders amounts to a considerable part of COVID-19-related losses. Our findings demonstrate that cost-benefit analysis of mobility restriction should include a forecast of mental disorder development in the population., Competing Interests: The authors of this study were supported by the Ministry of Education and Science of Russian Federation (grant No.075-11-2020-011 (13.1902.21.0040)). The grant supported both the research work and attending meetings and/or travel. The authors declare that there were no other funding sources or conflict of interest. The funding source (the Ministry of Education and Science of Russia) had no role in designing and conducting the study, collecting and analysing the data, writing the manuscript, or the decision to submit the manuscript. There was no other source of funding (including pharmaceutical companies). Co-authors of the study were not precluded from accessing the data. The co-authors accept responsibility to submit for publication., (© 2023 The Authors.)

Background: The control of tuberculosis (TB) may benefit from a prospective identification of areas where the incidence may increase in addition to the traditionally identified foci of high incidence. We aimed to identify residential areas with growing tuberculosis incidence rates and assess their significance and stability., Methods: We analysed the changes in TB incidence rates using case data georeferenced with spatial granularity to apartment buildings in the territory of Moscow from 2000 to 2019. We identified sparsely distributed areas with significant increases in the incidence rate inside residential areas. We tested the stability of found growth areas to case underreporting via stochastic modelling., Results: For 21 350 cases with smear- or culture-positive pulmonary TB among residents from 2000 to 2019, we identified 52 small-scale clusters of growing incidence rate responsible for 1% of all registered cases. We tested clusters of disease growth for underreporting and found them to be relatively unstable to resampling with case drop-out, but their spatial displacement was small. Territories with a stable increase in TB incidence rate were identified and compared to the rest of the city, which is characterised by a significant decrease in incidence., Conclusions: Identified areas with a tendency for an increase in the TB incidence rate may be important targets for disease control services., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Little is known about the dynamics of the early stages of untreated active pulmonary tuberculosis: unknown are both the rates of progression and the model "scheme". The "parallel" scheme assumes that infectiousness of tuberculosis cases is effectively predefined at the onset of the disease, and the "serial" scheme considers all cases to be non-infectious at the onset, with some of them later becoming infectious. Our aim was to estimate the progression of the early stages of pulmonary tuberculosis using data from a present-day population. We used the routine notification data from Moscow, Russia, 2013-2018 that contained the results and time of the last fluorographic screening preceding the detection of tuberculosis cases. This provided time limits on the duration of untreated tuberculosis. Parameters of TB progression under both models were estimated. By the goodness of fit to the data, we could prefer neither the "parallel", nor the "serial" model, although the latter had a bit worse fit. On the other hand, the observed rise in the fraction of infectious tuberculosis cases with the time since the last screening was explained by the "serial" model in a more plausible way - as gradual progression of some cases to infectiousness. The "parallel" model explained it through less realistic quick removal of non-infectious cases and accumulation of the infectious ones. The results demonstrate the potential of using such detection data enriched with reassessments of the previous screenings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The COVID-19 pandemic has created a public health emergency in Russia and across the world. The wavelike spread of the new coronavirus infection, caused by newly emerging variants of the coronavirus, has led to a high incidence rate in all subjects of the Russian Federation. It is becoming extremely topical to get the opportunity to manage the development of the epidemic and assess the impact of certain regulatory measures on this process. This will help government agencies make informed decisions to control the burden on healthcare organizations. It is often impossible to obtain such assessments without using modern mathematical models., Competing Interests: The authors declare that they have no conflicts of interest., (© Pleiades Publishing, Ltd. 2022, ISSN 1019-3316, Herald of the Russian Academy of Sciences, 2022, Vol. 92, No. 4, pp. 479–487. © Pleiades Publishing, Ltd., 2022.Russian Text © The Author(s), 2022, published in Vestnik Rossiiskoi Akademii Nauk, 2022, Vol. 92, No. 8, pp. 747–755.)

Objectives: To find residential areas with high incidence rate of tuberculosis in Moscow using spatio-temporal analysis of incidence data., Methods: We analyzed the spatial patterns of residence locations of smear or culture positive patients with pulmonary tuberculosis in Moscow. To identify clusters with high local incidence rates, the neighborhoods of detected cases were studied. We assessed the spatial and temporal stability of clusters., Results: For 19033 cases diagnosed with smear or culture positive pulmonary tuberculosis among residents of Moscow in 2000-2015 we identified 18 small-scale clusters of increased incidence rate responsible for 3% of all registered cases identified on a territory inhabited by only 1% of the population. Locations of clusters were sufficiently stable in space throughout the whole period. The local incidence rate inside clusters was significantly (3-4 times) higher than the city average during the whole observation period. The presence of clusters was associated with the incidence rate in the surrounding area. Socio-demographic characteristics of patients in clusters were not significantly different from the average characteristics of patients in the city., Conclusions: The detected small-scale clusters of increased incidence may be used to target active case finding for tuberculosis. The causes and mechanisms of cluster formation and stability need further study., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The United States Navy monitors the dose its radiation workers receive using the DT-702/PD thermoluminescent dosimeter, which consists of the Harshaw 8840 holder and the four-element Harshaw 8841 card. There were two main objectives of this research. In the first objective, the dosimeters were exposed to 100 Gy using electron and x-ray beams and found to respond approximately 30-40% lower than the delivered dose. No significant effect on the under-response was found when dose rate, radiation type, dosimeter position on the phantom, and dosimeter material were varied or when the card was irradiated while enclosed in its holder. Since the current naval policy is to remove from occupational use any thermoluminescent dosimeter with an accumulated deep dose equivalent of 0.05 Sv or greater, the functionality of the dosimeter was also investigated at deep dose equivalents of 0.05, 0.15, and 0.25 Sv using 60Co and 137Cs sources as the second main objective. All dosimeters were annealed following exposure and then exposed to 5.0 mSv from a 90Sr source. In all cases, the dosimeters responded within 3% of the delivered dose, indicating that the dosimeters remained functional as defined by naval dosimetry requirements. However, the anneal time required to clear the thermoluminescent dosimeter's reading was found to increase approximately as the cube root with the delivered dose.

Objective: To estimate tuberculosis (TB) incidence and case detection rate (CDR) using routine TB surveillance data only., Methods: A mathematical model of the case detection process, representing competition between disease progression and case finding, is proposed. The model describes disease progression as a two-stage process (bacillary and non-bacillary TB), and so relates the proportion of bacillary TB cases on detection to the effectiveness of detection. Thus, given the annual numbers of newly detected TB cases stratified by bacillary status, the model estimates detection rates, incidence and CDR. Routine notification data from eight provinces in Russia, 2000-2011, were used for the study., Results: Subnational level estimates of incidence and CDR were obtained. Incidence estimates varied by two-fold among the provinces; corrected CDR estimates varied by 1.5 times. The trend in the incidence estimates was similar to that in the World Health Organization estimates for the whole of Russia. The change in the trend in WHO CDR estimates in 2008-2009 was not supported by our estimates., Conclusion: The general approach that uses multistage models of disease progression and accordingly stratified notification data can be applied in various settings for the routine estimation of incidence and CDR.

This paper presents the results of an interlaboratory comparison of retrospective dosimetry using the electron paramagnetic resonance method. The test material used in this exercise was glass coming from the touch screens of smart phones that might be used as fortuitous dosimeters in a large-scale radiological incident. There were 13 participants to whom samples were dispatched, and 11 laboratories reported results. The participants received five calibration samples (0, 0.8, 2, 4, and 10 Gy) and four blindly irradiated samples (0, 0.9, 1.3, and 3.3 Gy). Participants were divided into two groups: for group A (formed by three participants), samples came from a homogeneous batch of glass and were stored in similar setting; for group B (formed by eight participants), samples came from different smart phones and stored in different settings of light and temperature. The calibration curves determined by the participants of group A had a small error and a critical level in the 0.37-0.40-Gy dose range, whereas the curves determined by the participants of group B were more scattered and led to a critical level in the 1.3-3.2-Gy dose range for six participants out of eight. Group A were able to assess the dose within 20 % for the lowest doses (<1.5 Gy) and within 5 % for the highest doses. For group B, only the highest blind dose could be evaluated in a reliable way because of the high critical values involved. The results from group A are encouraging, whereas the results from group B suggest that the influence of environmental conditions and the intervariability of samples coming from different smart phones need to be further investigated. An alongside conclusion is that the protocol was easily transferred to participants making a network of laboratories in case of a mass casualty event potentially feasible.

After studying the dependence of acute respiratory diseases of all etiologies on air temperature and population immunity dynamics, the authors proposed that the air temperature and the immunity level can affect disease resistance. Knowledge of the relationship between these factors must clarify the mechanisms that determine morbidity dynamics., (© Pleiades Publishing, Ltd. 2011.)

Imaging plates sensitive to beta rays were used to obtain the images of 90Sr in tooth samples taken from mammals collected in contaminated areas of the former Soviet Union. The average concentrations of 90Sr in the samples were determined by comparing the intensities of the luminescence using a single crystal of KCl. The results showed that the determined 90Sr concentration has a positive correlation with the soil contamination levels in the South Ural region. Tooth samples from both inside of the Semipalatinsk nuclear test site and the villages nearby have detectable amounts of 90Sr, indicating the possible presence of residual soil contamination. The present study demonstrates that using imaging plates is a very sensitive method to detect 90Sr in teeth as well as to estimate low-level 90Sr contamination in soil.

Population studies have shown that treatment with the antidiabetic biguanide metformin significantly reduced cancer risk. In our animal studies, metformin delayed the onset of mammary adenocarcinoma (MAC) in transgenic HER-2/neu mice but not the onset of spontaneous mammary tumors in female SHR mice. Pineal hormone also inhibits mammary carcinoma development in HER2/neu transgenic mice as well as in female SHR mice. Here we demonstrated that a combination of metformin and melatonin significantly inhibits growth of transplanted tumors in mice. Metformin (0.5 mg/ml in drinking water) increased mean life span by 8% and MAC latency by 13.2% (p < 0.05) in HER2/neu mice. The treatment with melatonin alone (2 mg/L in drinking water during the night time) or combined treatment with metformin (0.5 mg/ ml in drinking water during the day time) + melatonin (2 mg/L in drinking water during the night time) did not influence mammary carcinogenesis in the mice. The treatment metformin alone inhibited the growth of transplantable HER2 mammary carcinoma in FVB/N male mice by 46% at the 45(th) day after transplantation (p < 0.001). The combined treatment with metformin + melatonin significantly suppressed Ehrlich tumor growth (by 40%, p < 0.001). These results suggest that metformin may be useful in prevention and treatment of breast cancer.

A mathematical model of long-term immune defense against infection was used to estimate the energy involved in the principal processes of immune resistance during periods of health and infection. From these values, an optimal level of energy was determined for immune response depending on infection burden. The present findings suggest that weak but prevalent pathogens lead to latent or chronic infection, whereas more virulent but less prevalent pathogens result in acute infection. This energy-based approach offers insight into the mechanisms of immune system adaptation leading to the development of chronic infectious diseases and immune deficiencies.

Biological monitoring of dose can contribute important, independent estimates of cumulative radiation exposure in epidemiological studies, especially in studies in which the physical dosimetry is lacking. Three biodosimeters that have been used in epidemiological studies to estimate past radiation exposure from external sources will be highlighted: chromosome painting or FISH (fluorescence in situ hybridization), the glycophorin A somatic mutation assay (GPA), and electron paramagnetic resonance (EPR) with teeth. All three biodosimeters have been applied to A-bomb survivors, Chernobyl clean-up workers, and radiation workers. Each biodosimeter has unique advantages and limitations depending upon the level and type of radiation exposure. Chromosome painting has been the most widely applied biodosimeter in epidemiological studies of past radiation exposure, and results of these studies provide evidence that dose-related translocations persist for decades. EPR tooth dosimetry has been used to validate dose models of acute and chronic radiation exposure, although the present requirement of extracted teeth has been a disadvantage. GPA has been correlated with physically based radiation dose after high-dose, acute exposures but not after low-dose, chronic exposures. Interindividual variability appears to be a limitation for both chromosome painting and GPA. Both of these techniques can be used to estimate the level of past radiation exposure to a population, whereas EPR can provide individual dose estimates of past exposure. This paper will review each of these three biodosimeters and compare their application in selected epidemiological studies.

The aim of this paper is to analyze the lower limit of detection (LLD), linearity of dose response, variation of radiation sensitivity between different tooth enamel samples, and time/temperature stability of EPR biodosimetry in tooth enamel. The theoretical LLD is shown to be 0.46 mGy, which is far lower than the measured value of about 30 mGy. The main issues to lowering LLD are the differentiation of the radiation-induced component against the total EPR spectrum and the complex nature of the dose dependence of the EPR signal. The following questions are also discussed in detail: need for exfoliated or extracted teeth from persons of interest, accounting for background radiation contribution; conversion of tooth enamel absorbed dose to effective dose; accounting for internal exposure specifically from bone-seeking radionuclides. Conclusions on future development of EPR retrospective biodosimetry are made.

Spectral acquisition time is one of the limiting factors in electron paramagnetic resonance (EPR) retrospective biodosimetry in teeth. Acquisition times for one sample can be from 2 to 4h. This problem is even more acute for in vivo EPR measurements in L-band. Patients cannot be expected to remain stationary for these lengths of time. In order to overcome this limitation, we investigated the dependence of EPR dose measurements on the number of data points in an EPR spectrum. We have shown that this number could be reduced from 1024 to 256 (factor of 4 reduction in spectral acquisition time) at 5 mT magnetic field sweep without a loss of precision in the dose measurements.

Understanding the factors that determine the allocation and utilization of organism resources may provide an insight into the mechanisms of adaptation, ageing and reproduction. Resource allocation, which is regarded as a method of adaptation, increases fitness and is genetically controlled. Experiments with variable diet feeding of female Mediterranean fruitflies (Ceratitis capitata) demonstrated that the feeding regime dramatically influences lifespan, mortality and the reproduction of flies. An analysis of experimental data and numerical experiments reveals that resource allocation could explain lifespan increase when females are switched from a sugar-only to a protein-containing diet. The heterogeneity of the initial female cohort in terms of the total amount of resources and its allocation to the processes of maintenance and reproduction plays a significant role in this.

In this paper, we presented the results of analysis of experimental evidence for the decline of the human immune system functioning with age using mathematical model of immunosenescence. The most prominent changes in this system are related to the decline in the T-cellular immunity. These include the decline in the nai;ve T cells generation rate, shrinkage of the volume of the peripheral lymphoid tissue, decline of absolute and relative concentrations of nai;ve T cells in the blood, shortening of the average telomere length of T cells. These alterations in the immune system are responsible for sharp increase of morbidity and mortality caused by infectious agents at old ages. Analysis shows that concentrations of memory and nai;ve T cells in peripheral lymphoid tissue are the key variables in this process. Simulation experiments with our model show that the average life span of memory T cells must grow with age, and that decreasing of antigenic load led to considerable increase in organism's resistance in middle ages, but only to slight increase in old ages. Restriction in the rate of thymus involution resulted in an increase of organism's resistance to infections in old ages. However, this growth is accompanied by the decline of concentration of memory T cells and shortening of their life span. The proposed model describes the trade-off between concentrations of nai;ve and memory T cells and their potential to proliferate in human organism.

The present communication describes the technical aspects of the first application of an imaging plate for visualization of (90)Sr deposited in human teeth. The teeth were obtained from Techa River area residents who were exposed as a result of releases of radioactivity into the Techa River by the first Soviet nuclear plant Mayak in the early 1950s. The investigations form the basis for an experimental procedure for accurate mapping of the distribution of (90)Sr in teeth with an imaging plate. This new method can be used as an individual indicator of radionuclide intake. Its advantages are its high sensitivity (0.02 Bq/g mm(-2) of (90)Sr), it ability to examine small detectable cross-sectional areas of dental tissue (dentin) contaminated with (90)Sr (from 0.01 mm(2)), the nondestructive method of analysis, and the simplicity of use. The combined application of this method with EPR tooth biodosimetry can provide more accurate dose reconstruction and may lead to more effective radiation risk assessment.

During 1949-1956, the first Soviet nuclear weapons plant, Mayak, released about 7.6 x 10(7) m(-3) of liquid radioactive waste with a total activity of 10(17) Bq into the Techa River (Southern Urals, Russia). 90Sr contributed 11.6% to the total waste radioactivity. As a result of these radioactive discharges, about 28,000 local residents were exposed to ionizing radiation, and some of them received relatively high doses. Internal exposure of the population residing at the Middle and Lower Techa riverside was mostly from 90Sr deposited in bone and tooth tissues. In order to reconstruct radiation doses to this population group, a study of 35 teeth extracted from local residents was carried out using electron paramagnetic resonance measurements. A total of 73 samples from these 35 teeth (tooth enamel, 33; crown dentin, 20; and root dentin, 20) were prepared and measured with electron paramagnetic resonance. The study revealed high doses (up to 15 Gy) absorbed in tooth enamel of the individuals born during 1945-1949, which was attributed to very high local 90Sr concentration in tooth enamel of this particular age group in the population. The analysis presented here takes into account (a) the time courses both of the release/intake of 90Sr and of the tooth formation, and (b) expected variations in measured absorbed doses due to differing geometric sizes of tooth structures. This methodology enables a more consistent picture to be developed of the 90Sr intake by the Middle and Lower Techa riverside population, based on electron paramagnetic resonance tooth dosimetry.

The present note describes new advancements to a valued tool in retrospective biodosimetry that lower the threshold of detection of radiation dose to 29 mGy. The advanced method is based on the electron paramagnetic resonance measurements of stable radiation-induced radicals in tooth enamel. Earlier this method had been used only for reconstruction of high radiation doses obtained accidentally. New opportunity of reconstruction of doses lower than 100 mGy opens a new realm of possibilities for assessing the health effects of ionizing radiation at the natural radiation background level.

This paper addresses issues in the application of the electron paramagnetic resonance (EPR) retrospective dosimetry with dental tissues exposed by radionuclides accumulated in the dentin. A simple dosimetric model of a tooth incorporating 90Sr is presented. The tooth is modelled as two concentric cylinders: the inner cylinder composed of dentin, and the outer cylindrical shell of enamel. Extensive Monte Carlo calculations were done to obtain the distributions of absorbed dose in dentin and enamel for teeth of different sizes. The results were used to calculate the mean absorbed doses in enamel that are directly measurable by EPR. A relationship between such measured doses and the specific activity of 90Sr in dentin was derived based on a simple model of 90Sr accumulation. The roles of different tooth tissues as dose detectors are analysed, and the importance of dentin as a dosimetric material for internal exposure is pointed out.

People living on the banks of the Techa river were exposed to 90Sr in the early 1950s. Data obtained by radiochemical measurements of extracted permanent teeth, 90Sr autopsy measurements in bone and tooth samples, in vivo measurements of surface beta activity of the anterior teeth and whole-body counter (WBC) measurements of 90Sr in the skeleton have been analyzed. Surface beta activity measurements indicate a biological half-life of 90Sr of about 35 years in enamel. The WBC measurements have been performed since 1974 and a model for the age-dependent strontium retention in human bone has been used to extrapolate to previous time periods when the other measurement results were obtained. For the first decade after the intake, the ratio of the 90Sr concentrations in teeth and bones were found to decrease with age at the time of major intake, from about 10 for 1-year-old children to about 0.3 for adults. There was a considerable variability of individual data within each age group. For adults, the correlation between 90Sr in skeleton and teeth was not high at 0.47 according to radiochemical data for posterior teeth (molars and premolars) and 0.43 according to measurements of surface beta activity for anterior teeth. For children and adolescents there was no correlation between individual measurements in the skeleton and teeth. The absorbed dose in enamel due to 90Sr in dentine has been calculated by Monte Carlo simulations of the electron transport. The results are in agreement with EPR measurements of the absorbed dose in the enamel of persons exposed, mainly due to 90Sr ingestion.

A software code was developed for fitting the EPR tooth enamel spectrum using linear combinations of Gaussian functions. The software is fastening EPR dose reconstruction for routine applications. The verification of the software was done comparing with the selective saturation method as an independent procedure of signal evaluation. Both methods were applied for the dose reconstruction of 13 teeth mostly from the Techa riverside. The evaluated doses by the two methods demonstrate an excellent agreement.

This paper focuses on the opportunities to gain risk assessment information from populations exposed to ionizing radiation. Details are presented on the scale of the nuclear events in several areas within the former Soviet Union. An overview of the issues associated with dose reconstruction by electron paramagnetic resonance (EPR) is given. Principles and outline of the EPR tooth enamel dose assessment are described. Technical details, the latest achievements and the problems of each procedural step are analyzed. In addition, the present accuracy of the EPR dose reconstruction, its problems and cost are discussed.

We propose a new approach to the additive dose method in EPR dosimetry studies for tooth enamel specimens. We outline a specialized routine whereby the sample may be left for the most part unirradiated, while only a small aliquot of the sample will be additively irradiated to relatively large doses. The routine is done in such a way so as not to significantly compromise either precision or accuracy of the dose reconstruction. It is also demonstrated that the overall throughput of the dose reconstruction is not appreciably compromised. With this potential ability, the utility of an international dose/sensitivity standard for EPR dosimetry of teeth is considered.

The present paper describes results of the first independent evaluation of the accuracy of the dose-reconstruction technique by electron paramagnetic resonance using tooth enamel. Each of twenty-four teeth donated by Mayak nuclear workers with known occupational radiation exposure histories was cut into two parts so that each tooth could be shared for blind electron paramagnetic resonance examination by at least two of the four laboratories participating in the study. The mean difference (+/- SD) between electron paramagnetic resonance estimates of the paired samples of each tooth shared by the two laboratories in best agreement was 0.02 +/- 0.15 Gy. Mayak workers can be classified into two groups: modern workers (after 1961) having reliable official dose information and earlier nuclear workers whose dose information is less reliable because they were exposed mainly before 1961. Film badges did not contain filters until 1954. Doses in this earlier group are much higher (up to 5 Gy). Comparison of the electron paramagnetic resonance results with tooth doses calculated from official film-badge doses showed a close agreement for the first group, whereas in the second group, official doses appeared to be slightly higher than the electron paramagnetic resonance doses. The results suggested a possibility that the official doses were somewhat overestimated among the high-dose-exposed workers. Consequently, cancer risks derived from this high-dose group might tend to be slightly underestimated.

The results of the EPR dose reconstruction in calcified tissues of dog injected with 90Sr are presented. It has been established that there is no essential difference in the values of doses absorbed in tooth tissues of teeth in symmetric positions in the mouth, whereas a significant difference occurs in the values of absorbed doses in teeth in non-symmetric positions. In the case of 90Sr internal exposure the dose reconstruction in crown dentine plays an important role. It has been found that its quantity is close to the dose in diaphyseal cortical bone of the femur, dose at the endosteal bone surface and in femural fatty marrow. The fact that these values exceed doses absorbed in tooth enamel points out the predominant contribution of internal exposure. The highest absorbed doses have been observed in metaphyseal trabecular femur bones, tooth alveolar bone walls, and cortical and trabecular vertebra that can be considered as suitable candidates for biomarkers of internal 90Sr exposure for post-mortal autopsy. The satisfactory correlation has been found between the doses reconstructed in calcified dog tissues and the doses measured by EPR in alanine dosimeters fixed in (or nearby) the sites of autopsy of bones/teeth. The experiments provide support for the view that EPR retrospective dosimetry with calcified tissues for internal exposure is unique in providing useful information on the doses obtained.

In this article we discuss examples of challenging problems in retrospective dosimetry and describe some promising solutions. The ability to make measurements by accelerator mass spectrometry and luminescence techniques promises to provide improved dosimetry for regions of Belarus, Ukraine and Russian Federation contaminated by radionuclides from the Chernobyl accident. In addition, it may soon be possible to resolve the large neutron discrepancy in the dosimetry system for Hiroshima through novel measurement techniques that can be used to reconstruct the fast-neutron fluence emitted by the bomb some 51 years ago. Important advances in molecular cytogenetics and electron paramagnetic resonance measurements have produced biodosimeters that show potential in retrospective dosimetry. The most promising of these are the frequency of reciprocal translocations measured in chromosomes of blood lymphocytes using fluorescence in situ hybridization and the electron paramagnetic resonance signal in tooth enamel.

A review is given on the major technological and methodological aspects of retrospective ESR dosimetry with tooth enamel. Topics include the collection and preparation of samples, the evaluation, treatment and interpretation of the ESR signals, and the procedure of dose reconstruction. Two pathways are described to differentiate between doses from different internal and external sources. They are based on dose comparisons as evaluated from different tooth issues or from dose vs age dependencies obtained by ESR dosimetry from populations with different exposure conditions. The concepts given are illustrated by recently achieved ESR doses that were reconstructed from teeth of radiation workers and members of the public of the Southern Urals region, Russia.

During 1949-1956, about 76 x 10(6)m3 of radioactive liquid waste containing a total activity of 10(17) Bq was discharged into the Techa River by the first Russian industrial nuclear facility Mayak. As a consequence, the population living in the river valley received considerable internal and external radiation doses. The results of a first application of electron paramagnetic resonance (EPR) of tooth enamel for a retrospective individual dose evaluation of the residents of the Techa riverside are presented. Three main contributions to the dose absorbed in tooth enamel have been considered: external exposure mainly from the Techa River sediments, internal exposure mainly due to 90Sr; and background radiation including all other sources of exposure except the Techa River. The teeth of 86 inhabitants of the town Kamensk-Uralskii were analysed to determine the age-dependent contribution of the background radiation to the enamel dose. For 22 residents of the middle and lower Techa riverside, measurements of the 90Sr whole-body content and EPR measurements of the absorbed dose in enamel were used to establish a correlation between these two quantities. Finally, absorbed doses in the enamel of five residents of the upper Techa riverside were determined by EPR method. Contributions of the background radiation and the internal 90Sr contamination were subtracted to determine the external exposure of the residents.

Mean annual occupational exposures are reported for radiation workers at the first Russian industrial nuclear facility 'Mayak', South Ural region, for the period 1948-1988. The underlying individual doses originate from the register of the in-plant radiation safety department and are based on local film dosimetry results. Differentiation is made between personnel working at reactor and radiochemical processing plants. Verification of summed film doses is performed by means of ESR dose reconstruction using extracted teeth from selected individuals. Explanations are given for observed discrepancies between the reconstructed individual doses and original integrated film dosimetry results. The research potential of combined dose information from specific tooth enamel and dentine are shown.

The method of selective saturation proposed is based on the difference in the microwave (mw) power dependence of the background and radiation induced EPR components of the tooth enamel spectrum. The subtraction of the EPR spectrum recorded at low mw power from that recorded at higher mw power provides a considerable reduction of the background component in the spectrum. The resolution of the EPR spectrum could be improved 10-fold, however simultaneously the signal-to-noise ratio was found to be reduced twice. A detailed comparative study of reference samples with known absorbed doses was performed to demonstrate the advantage of the method. The application of the selective saturation method for EPR dosimetry with tooth enamel reduced the lower limit of EPR dosimetry to about 100 mGy.

As a result of EPR investigations on tooth enamel from radiation workers of the Russian nuclear facility "Mayak" in South Ural, individual doses are reconstructed. The individual doses obtained range up to 3.89 Gy. It is shown that the reconstructed doses are unreasonable until very good agreement with the original personal doses as provided by the radiation protection authority. The findings first prove the applicability of EPR dosimetry on tooth enamel for a life-time including accident dose reconstruction of individuals as a basis for epidemiological studies.

We present an approach to studying theoretically the regularities and the kinetic characteristics of influenza A virus (IAV) infection in man. The estimates of the "numbers" (Zinkernagel et al., 1985) characterizing evolutionary established interferon and immune responses in uncomplicated IAV infection are explored by developing a multiparameter mathematical model which allows direct quantitative references to the biological reality. The system of equations of the mathematical model of antiviral immune response, applied earlier to acute hepatitis B virus infection (Marchuk et al., 1991a, b), is modified and extended to describe the joint reaction of the interferon and immune systems in IAV infection. Macrophages infiltrating the airway's epithelium are considered to be the principal source of interferon that induces antiviral resistance in lung epithelial cells. The model is formulated as a delay-differential system with about 60 parameters characterizing the rates of various processes contributing to the typical course of IAV infection. The key aspect of the adjustment between the model and various data on the immunity to influenza is the derivation of a consistent data set--the generalized picture of uncomplicated IAV infection. It serves as a consistent theoretical definition of the structure of the normal course of the infection and the antiviral immune response suitable for model fitting. The parameter estimates for the processes considered in the model are carefully discussed. The quantitative model is used to study the organization and dynamic properties of the processes contributing to IAV infection. The threshold condition for immune protection of virus-free host to infection with IAV is analyzed. The relative roles of humoral, cellular and interferon reactions for the kinetics of the uncomplicated IAV infection are studied. The contribution of parameters of virus-sensitive tissue, interferon and IAV-specific immune processes to the variations of duration and severity of the infection is quantitatively estimated by sensitivity studies. It is shown that the variations in the parameters of a virus-epithelial cell system are more influential on the severity of the infection rather than that of the antiviral immune response. The need for fine co-ordination of the kinetics of the non-specific interferon response and the adaptive antigen-specific immune reactions to provide recovery from the infection is illustrated.

A mathematical model of the T-lymphocyte proliferation process (in vivo and in vitro) is presented. This model takes into account cell-cycle progression and the regulation by lymphokines (lymphocyte activating factor interleukin 1 and T-cell growth factor interleukin 2). Using data on the generalized picture of the short-term course of viral hepatitis B, the parameter estimation procedure is carried out. The possibility of immunocorrection (by means of injection of a pharmacologic dose of IL-2) during the immune response to viral hepatitis B with T-lymphocyte deficiency is shown.

The present approach to the mathematical modelling of infectious diseases is based upon the idea that specific immune mechanisms play a leading role in development, course, and outcome of infectious disease. The model describing the reaction of the immune system to infectious agent invasion is constructed on the bases of Burnet's clonal selection theory and the co-recognition principle. The mathematical model of antiviral immune response is formulated by a system of ten non-linear delay-differential equations. The delayed argument terms in the right-hand part are used for the description of lymphocyte division, multiplication and differentiation processes into effector cells. The analysis of clinical and experimental data allows one to construct the generalized picture of the acute form of viral hepatitis B. The concept of the generalized picture includes a quantitative description of dynamics of the principal immunological, virological and clinical characteristics of the disease. Data of immunological experiments in vitro and experiments on animals are used to obtain estimates of permissible values of model parameters. This analysis forms the bases for the solution of the parameter identification problem for the mathematical model of antiviral immune response which will be the topic of the following paper (Marchuk et al., 1991, J. theor. Biol. 15).

Considering the mathematical model of antiviral immune response, we describe a method of fitting the model to the data characterizing acute viral hepatitis B. The corresponding procedure employs an idea of sequential parameter estimation to make the problem of fitting manageable. The underlying mechanisms responsible for the quantitative manifestations of the four basic phases of acute hepatitis B are used to select the model parameters. The identified model of acute hepatitis B is then tested with regard to the following situations: the effect of HBsAg-specific antibodies on HBV challenge; the vaccination and the resistance to challenge using live hepatitis B virus; the dose of viruses--the incubation time relationships. The sensitivity of the model with respect to parameters variations is then analysed. The developed model allows us to quantitatively simulate the basic features of the antiviral immune response during acute hepatitis B and some closely related phenomena.