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P Jacob

Publications and source records attributed to P Jacob.

At least 37 records · Page 2Linked to original sources

Mechanistic modelling in large case-control studies of lung cancer risk from smoking.

The two-step clonal expansion (TSCE) model is applied to large case-control studies, frequency matched for age, which allow estimation of the RR of lung tumour risk caused by smoking. For estimating background hazard rates, mortality data from the study areas are used to supplement the case-control data. Two approaches are used to analyse the data, based on the unconditional and the conditional likelihoods. They are demonstrated to give nearly identical results. Some model diagnostics are performed and demonstrate a good model fit. Our results indicate that smoking acts on the promotion and transformation parameters, but not on the initiation parameter of the TSCE model. The fitted relative risk of current smokers peaks between ages 50 and 60 years. The relative risk of male ex-smokers decreases strongly with time since end of exposure, but does not reach the risk of non-smokers, and does not decrease as much as for female ex-smokers.

Adult↗

External exposure of the population living in areas of Russia contaminated due to the Chernobyl accident.

An updated version of external dose modeling is presented with reference to the population in Russian areas contaminated due to the Chernobyl accident. An earlier version has been modified by applying a study time interval with a starting point immediately after radionuclide deposition (rather than 4 years after the accident as applied earlier) and by introducing an estimate of individual dose distributions. New input data to the model are the nuclide-specific composition of the deposit, additional data about migration of caesium in soil, time dependence of location factors and uncertainty distributions of all input parameters. Model results (i.e. effective dose-rates and accumulated effective doses) from external exposure for the rural and urban populations in contaminated areas of Russia during 100 years after the accident are presented. Radionuclide contributions to the dose during various time intervals after the accident have been estimated. The model has been validated by measurements of absorbed dose-rate in air during the first 30 days after the accident and by TLD measurements of individual external doses among inhabitants of contaminated rural settlements in the year 1993. Both the measurements and model show that the geometric mean of individual external doses is about 10% lower than the arithmetic mean and the upper bound of the 95% confidence range is larger by a factor of about 2.

Adolescent↗

Investigations of thermoluminescence dosimetry in the Techa river flood plain: analysis of the new results.

The Techa river region was highly contaminated due to radioactive releases from a nuclear production facility in the period from 1949 to 1956. The inhabitants of the upper Techa river settlements received significant doses of external radiation. The majority of the houses in the upper Techa river villages were demolished after the evacuation of the population in 1956. Only three buildings (red-brick construction) in the former village of Metlino can still be used for thermoluminescence (TL) investigations in an external dose reconstruction study. The radiation source configuration changed in 1956 after an artificial reservoir was created next to Metlinsky pond. Preliminary TL studies showed good properties of the bricks that were sampled from the buildings. This paper presents an analysis of new results of TL investigations obtained on the samples collected from different walls of the buildings. The highest dose values in the range 1-4 Gy were found in bricks collected from the walls of building exposed to the artificial reservoir (Reservoir-10) and values of 1-1.5 Gy were found next to the Metlinsky pond shoreline. The measurements of the radiation source geometry were carried out simultaneously with the dose rates, radionuclide concentration in water and bottom sediments near the wall facing the old river bed. The measurements allow a validation of models used in the current Techa River Dosimetry System (TRDS-2000) to estimate external doses of the former inhabitants of the upper Techa riverside. In particular, the results can be applied for a more correct description of the source geometry in the settlement.

Fresh Water↗

Thin layer alpha-Al2O3:C beta dosemeters for the assessment of current dose rate in teeth due to 90Sr intake, and comparison with electron paramagnetic resonance dosimetry.

The use of thin-layer alpha-Al2O3:C thermoluminescent detectors (TLDs) for the assessment of current beta dose rate in human teeth due to 90Sr intake is investigated. The teeth used in this study were collected from members of the Techa river population who were exposed to radiation as a result of releases of the Mayak plutonium production facilities (Southern Urals-Russia) between 1949 and 1956. The beta dose rates from different parts of the tooth (enamel, crown dentine, and root) were determined by storing the detectors over the samples in a shielded environment. The cumulative dose measured by electron paramagnetic resonance (EPR) in different dental tissues is found to be proportional to current dose rate obtained from alpha-Al2O3:C thermoluminescence dosemeters. The retention of 90Sr in various parts of the teeth is discussed.

Aluminum Oxide↗

Simulation of 125I induced DNA strand breaks in a CAP-DNA complex.

The E. coli catabolite gene activator protein (CAP)-DNA complex with 125I located at the position of the H5 atom of the cytosine near the centre was incorporated into the PARTRAC track structure code. DNA strand breaks due to irradiation were calculated by track structure and radical attack simulations; strand breaks due to neutralisation of the highly charged 125Te ion were derived from a semi-empirical distribution. According to the calculations, the neutralisation effect dominates the strand breakage frequency at 2 bases away from the 125I decay site on both strands. The first breakage distribution counted from a 32P labelled end on the strand with 125I agreed well with experimental data, but on the opposite strand, the calculated distribution is more concentrated around the decay site and its yield is about 20% larger than the measured data.

Base Pairing↗

Monte Carlo simulation of DNA damage by low LET radiation using inhomogeneous higher order DNA targets.

To test possible effects of the heterogeneous nature of the cell nucleus on simulation results of radiation-induced DNA damage, inhomogeneous targets have been implemented in the biophysical code PARTRAC. The geometry of the DNA and the histones was defined by spheres around the constituent atoms. Electron cross sections in liquid water were scaled according to the mass density of the different materials, whereas photon cross sections were derived from the sum of the cross sections for the constituent atoms. In the case of higher energy electrons the simulations show an increase of energy deposition in the DNA proportional to its high mass density. For photons with energies in the range of the carbon and the oxygen K-shell (0.28-0.53 keV), cross sections of DNA are larger than those of water, leading to an increased yield of strand breaks per average absorbed dose in the cell nucleus.

Computer Simulation↗

Possible implications of non-linear radiobiological effects for the estimation of radiation risk at low doses.

Possible implications of the effects of low LET radiation on the induction of cancer at low doses are studied. Low dose hypersensitivity and adaptive response were identified as candidates which may give a non-linear dose effect curve for acute exposures, whereas adaptive response may influence protracted exposures. In this paper acute exposures are studied. Several radiobiological reports on studies with mammalian cell lines have indicated the presence of a hypersensitive region in the radiation survival response at low doses followed by an increase in radioresistance. The two step clonal expansion (TSCE) model for the process of carcinogenesis was adapted in such a way that cell killing after acute radiation induces increased clonal expansion for some time and thus gives a promoting effect of radiation. As a first step, the Radiation Effects Research Foundation (RERF) data on the lung cancer incidence are fitted to study how such a model would influence the assessment of the cancer risk at low doses.

DNA Repair↗

Simulation of DNA damage after proton and low LET irradiation.

A module for proton track structure simulation in liquid water was implemented in the biophysical model PARTRAC. Simulated tracks of energy deposition events from the radiation under investigation were superimposed on a higher-order DNA target model describing the whole genome inside a human cell. The parameters controlling DNA damage from direct and indirect effects were adapted to agree with yields and pathway contributions derived from gamma ray irradiation experiments. Single and double strand break (DSB) induction was simulated for irradiations by protons, photons and electrons over a wide range of initial energies. The relative biological effectiveness for DSB induction after proton irradiation was found to rise from 1.2 at 5 keV.micron-1 to about 2.5 at 70 keV.micron-1. About half of this growth resulted from an increased production of DSB clusters associated with small (< 10 kbp) fragments.

Computer Simulation↗

First international intercomparison of luminescence techniques using samples from the Techa River Valley.

Bricks collected from a contaminated village (Muslyumovo) of the lower Techa river valley, Southern Urals, Russia, were measured using thermoluminescence and optically stimulated luminescence by four European laboratories and a U.S. laboratory to establish and compare the applied dose reconstruction methodologies. The bricks, collected from 60-100-year-old buildings, had accumulated a relatively high dose due to natural sources of radiation in the brick and from the surrounding environment. This work represents the results of a first international intercomparison of luminescence measurements for bricks from the Southern Urals. The luminescence measurements of absorbed dose in bricks collected from the most shielded locations of the same buildings were used to determine the background dose due to natural sources of radiation and to validate the age of the bricks. The absorbed dose in different bricks measured by four laboratories using thermoluminescence and optically stimulated luminescence at a depth of 10 +/- 2.5 mm from the exposed brick surface agreed within +/-21%. After subtraction of the natural background dose, the absorbed dose in brick due to contaminated river sediments and banks was calculated and found to range between 150 and 200 mGy. The cumulative doses in brick due to man-made sources of radiation at 100 and 130 mm depths in the bricks were also measured and found to be consistent with depth dose profiles calculated by Monte Carlo simulations of photon transport for possible source distributions.

Background Radiation↗

Cardiovascular effects of carbon monoxide and cigarette smoking.

OBJECTIVES: This study was designed to compare the effects of inhaled carbon monoxide (CO), administered to achieve concentrations similar to those found in cigarette smoking, with the effects of cigarette smoking and air inhalation on heart rate and blood pressure, catecholamine release, platelet activation and C-reactive protein (CRP), a marker of inflammation. BACKGROUND: Carbon monoxide may contribute to smoking-induced cardiovascular disease. Exposure to environmental CO has been associated with increased cardiovascular morbidity and mortality. Animal and in vitro studies suggest that CO may contribute to atherosclerosis and endothelial injury. There is conflicting evidence about the hemodynamic consequences of exposure to CO and its role in platelet activation. METHODS: In a single-blind, crossover design, 12 healthy smokers inhaled CO at 1,200 ppm to 1,500 ppm to simulate CO intake from cigarette smoking, inhaled air on a similar schedule and smoked 20 cigarettes per day, each for seven days. Mean carboxyhemoglobin was 5 +/- 1% on CO treatment, 6 +/- 1% while smoking and 0.4 +/- 0.2% on air inhalations. RESULTS: There was no difference in blood pressure between the treatments. Mean heart rate was higher during cigarette smoking compared with CO and air inhalations (75 beats/min vs. 66 beats/min; p < 0.05). Plasma levels of platelet factor 4 and CRP and urine epinephrine and norepinephrine were higher while smoking, with no effect of CO compared with air. CONCLUSIONS: Carbon monoxide administered under conditions similar to those of cigarette smoking had no significant effect on blood pressure, heart rate, plasma catecholamines, platelet aggregation or CRP. The short-term chronotropic effect, adrenergic-activating, platelet-activating and CRP-increasing effects of smoking in healthy smokers are probably due to components of cigarette smoke other than CO.

Adult↗

Phase transfer and freezing processes investigated on acoustically levitated aqueous droplets.

An acoustic trap was designed and constructed to investigate, on a microscale, physicochemical processes relevant to the troposphere, mainly focusing on the temperature range below 0 degrees C. Droplets ranging from 0.5 nL to 4 microliter (0.1 to 2 mm in diameter) were introduced into the cooled reaction chamber by means of a piezo-driven micro pump with a reproducibility better than 5%. Up-take of H2O2 from the gas phase by the levitated droplet was measured and calibrated by in-situ chemiluminescence. Freezing of stably positioned droplets was observed and documented by means of a microscope and a video camera; this demonstrated the usefulness of the technique for simulation and investigation of cloud processes. Ex-situ microanalysis of sub-microliter droplets by use of a fiber optic luminometer was also shown to be a suitable means of investigating relevant physicochemical processes on a micro scale.

Journal Article↗

Uncertainty analysis of the external gamma-dose rate due to the variability of the vertical distribution of 137Cs in the soil.

The external gamma-dose rate at 1 m height above a flat area due to the presence of fallout radiocesium in the soil is frequently calculated from the observed depth profile of the 137Cs activity as well as the soil mass per unit area. At a given site, these depth profiles may, however, vary considerably, thus introducing an uncertainty to the external gamma-dose calculated in this way. To assess this source of uncertainty for a typical grassland site, the activity of Chernobyl-derived 137Cs and the wet bulk density in the three upper soil layers at 100 plots in a 100 m x 100 m pasture were determined. Analysis of these data shows that the frequency distribution of the dose rates calculated from the corresponding depth profiles of all plots is similar to a log-normal distribution (mean 25 nGy h-1, median 22 nGy h-1, standard deviation 11 nGy h-1; range 1.6-56 nGy h-1). The various sources which contribute to the uncertainty of the dose rate are quantified. The semi-variogram indicates that any spatial dependence of the dose rates occurs on this pasture only over distances that are smaller than the shortest sampling interval (here about 10 m). It is estimated which errors have to be expected for the median dose rate when the depth profiles of 137Cs and of the wet bulk density are determined only for a small number of plots. It is preferable to calculate the mean dose rate as a mean from the n individual dose rates rather than from an averaged 137Cs depth profile of the n plots.

Agriculture↗

Remediation strategies for rural territories contaminated by the Chernobyl accident.

The objective of the present paper is to derive remediation strategies for rural settlements contaminated by the Chernobyl accident in which annual doses to a critical group still exceed 1 mSv. Extensive radioecological data have been collected for 70 contaminated settlements. A dose model based on these data resulted in estimates that are on average close to and a bit less than the official dose estimates ('catalogue doses') published by the responsible Ministries of Belarus, Russia and Ukraine. For eight remedial actions that can be applied on a large scale, effectiveness and costs have been assessed in light of their dependence on soil type, contamination level and on the degree of previous application of remedial actions. Remediation strategies were derived for each of the 70 settlements by choosing remedial actions with lowest costs per averted dose and with highest degree of acceptability among the farmers and local authorities until annual doses are assessed to fall below 1 mSv. The results were generalised to 11 contamination/internal-dose categories. The total numbers of rural inhabitants and privately owned cows in the three countries distributed over the categories were determined and predicted until the year 2015. Based on these data, costs and averted doses were derived for the whole affected population. The main results are (i) about 2000 Sv can be averted at relatively low costs, (ii) the emphasis on reducing external exposures should be increased, (iii) radical improvement of hay-land and meadows and application of Prussian blue to cows should be performed on a large scale if annual doses of 1 mSv are an aim to be achieved, (iv) additional remedial actions of importance are fertilising of potato fields, distribution of food monitors and restriction of mushroom consumption, and (v) for inhabitants of some settlements (in total about 8600) annual doses cannot be reduced below 1 mSv by the remedial actions considered.

Algorithms↗

Important factors governing exposure of the population and countermeasure application in rural settlements of the Russian Federation in the long-term after the Chernobyl accident.

Rural settlements located in areas of the Russian Federation contaminated after the Chernobyl accident and exceeding an annual dose of 1 mSv a-1 have been classified according to 137Cs contamination density, internal dose and the neighbourhood of forests. It has been shown that, with the exception of the most contaminated areas, the internal doses decreased in accordance with a decline in 137Cs availability for plant root uptake. An inverse tendency was observed in areas with 137Cs contamination above 555 kBq m-2 which can be explained by a reduction or even termination of countermeasure application and by an increasing consumption of forest products in areas where restrictive countermeasures are still implemented. Twenty-seven settlements have been studied to estimate the effectiveness of countermeasures applied previously and to identify the most important factors governing the radiation exposure to the population and its change with time. It has been shown that the effectiveness of countermeasures which resulted in a decrease of up to 40% of doses has a tendency to decline in the long term. The need for continuation of remediation in rural settlements was evaluated both for selected settlements and extrapolated to the whole contaminated area and it has been shown that the application of countermeasures will be of importance at least up to the year 2045. Rather high effectiveness in terms of internal dose reduction (factor of 2-2.5) of radical improvement (disking, ploughing and reseeding) and administration of Cs binders to animals (Ferrocyn) was demonstrated for the selected settlements. It could be demonstrated that for forest-remote settlements there is a linear dependence between internal dose normalised to the density of contamination and the proportion of peat soils around settlements. For near-forest settlements, this dependence was less pronounced which can be explained by the high contribution of forest food products to the internal dose. Milk is still the major dose-forming product in rural Russian settlements (its contribution to internal dose in forest-remote settlements is above 70%); however, in near-forest settlements, the contribution of mushrooms to the internal dose is comparable to the contribution from milk.

Agriculture↗

Trans-3'-hydroxycotinine: disposition kinetics, effects and plasma levels during cigarette smoking.

AIMS: (3'R,5'S)-trans-3'-hydroxycotinine (3-HC) is a major metabolite of nicotine. The aim of this study was to characterize the disposition kinetics of 3-HC in healthy smokers, including metabolism to (3'R,5'S)-trans-3'-hydroxycotinine glucuronide (3-HC-Gluc). We also studied pharmacologic responses to 3-HC and plasma levels of 3-HC in a group of smokers. METHODS: Eight cigarette smokers were studied on a clinical research ward. After 5 days of supervised nonsmoking, each subject received an intravenous infusion of 3-HC, 4 microg x kg(-1) x min(-1) for 60 min. Plasma and urine levels of 3-HC and 3-HC-Gluc and cardiovascular and subjective responses were examined. Plasma levels of 3-HC, nicotine, and cotinine were measured in 62 smokers on up to three occasions. RESULTS: The total plasma clearance of 3-HC averaged 1.3 ml x min(-1) x kg(-1), of which 63% was renal excretion of unchanged drug. An average of 29% of the dose was excreted as 3-HC-Gluc. 3-HC did not have nicotine-like cardiovascular effects. CONCLUSIONS: These findings extend our understanding of the quantitative nature of nicotine metabolism. Such data may be of use in quantitating human exposure to nicotine from tobacco and in studying individual variability in nicotine metabolism.

Adult↗

Age- and sex-specific relative thyroid radiation exposure to 131I in Ukraine after the Chernobyl accident.

The age- and sex-dependence of the 131I induced count rates is determined for the measurements performed in Ukraine after the Chernobyl accident on the thyroids of over 60,000 persons. For this, the individual measurements are scaled in such a way that the mean values over age and sex on one side and the mean values over measurement series on the other side are normalized to one. The resulting distribution of all scaled measurements is roughly log-normal. Half of them lie within a factor 1.6 of the median. 131I induced count rates have a minimum at birth year 1986, about half the value of adults. The maximum count rates with about 30% above adults are reached for males around age 16 y. The count rates are up to about 40% (at age 14-17 y) higher for males than for females. The results are within statistical uncertainties independent of the geographical area and the urban or rural nature of the settlements. Starting from the relative count rates, the age- and sex-dependence is calculated for the thyroid activities 1 mo after the accident for the integrated activities and for the doses. The dose of young children is a factor of about 6.5 higher than that of adults. Uncertainties are estimated throughout.

Adolescent↗

Correction factors in the EPR dose reconstruction for residents of the Middle and Lower Techa riverside.

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.

Age Factors↗