ABSTRACT Occupational exposure to wood dust and biohazards associated with wood dust (endotoxins, (1->3)-b-D-glucans, Gram (-)ve bacteria and fungi), their correlation to respiratory function, and symptoms among woodworkers have been investigated in the present study. Wood dust, endotoxins, and allergenic fungi are the main hazards found in woodworking environments. Relatively very few studies have been done on wood dust exposure. The present study was designed to comprehensively investigate the health effects of wood dust exposure, and in particular provide new information regarding: Exposure to (1->3)-b-D-glucans in an occupational environment; Levels of exposure to wood dust and biohazards associated with wood dust in different woodworking environments; Correlations among personal exposures, especially correlations between (1->3)-b-D-glucans and fungi exposures, and endotoxins and Gram (-)ve bacteria exposures; Effects of personal exposure to biohazards on lung function; Effects of personal exposure to biohazards on work-related symptoms; and Determinants of inhalable exposures (provide which factors in the environment influence the personal inhalable exposures). Workers at four different woodworking processes; two logging sites, four sawmills, one major woodchipping operation and five joineries situated in the state of New South Wales in Australia were studied for personal exposure to inhalable dust (n=182) and respirable dust (n=81), fungi (n=120), Gram (-)ve bacteria (n=120), inhalable endotoxin (n=160), respirable endotoxin (n=79), inhalable (1->3)-b-D-glucan (n=105), and respirable (1->3)-b-D-glucan (n=62). The workers (n=168) were also tested for lung function. A questionnaire study (n=195) was carried out to determine the prevalence of work-related symptoms. The geometric mean inhalable exposure at logging sites was 0.56 mg/m3 (n=7), sawmills 1.59 mg/m3 (n=93), the woodchipping mill 1.86 mg/m3 (n=9) and joineries 3.68 mg/m3 (n=66). Overall, sixty two percent of the exposures exceeded the current standards. Among joineries, 95% of the hardwood exposures and 35% of the softwood exposures were above the relevant standards. Compared with green mills, the percentage of samples, which exceeded the hardwood standard was high for dry mills (70% in dry mills, 50% in green mills). The respirable dust exposures were high at the joineries compared with the other worksites. Exposure levels to fungi at logging sites and sawmills were in the range 103-104 cfu/m3, woodchipping 103-105 cfu/m3 and joineries 102-104 cfu/m3. The predominant fungi found at sawmills were Penicillium spp. High exposure levels of Aureobasidium pullulans were also found at two sawmills. At the woodchipping mill the predominant species were Aspergillus fumigatus, Penicillium spp., and Paecilomyces spp. The sawmills, which employed kiln drying processes, had lower exposure levels of fungi compared with the green mills. Those workplaces which had efficient dust control systems showed less exposure to fungi and bacteria. Although mean endotoxin levels were lower than the suggested threshold value of 20 ng/m3, some personal exposures at sawmills and joineries exceeded the threshold limit value. The mean inhalable (1->3)-b-D-glucan level at the woodchipping mill was 2.32 ng/m3, at sawmills 1.37 ng/m3, at logging sites 2.02 ng/m3, and at joineries 0.43 ng/m3. For the respirable size fraction, mean endotoxin and mean (1->3)-b-D-glucan concentrations were much lower, being similar to observed dust concentrations. Significant correlations were found between mean inhalable endotoxin and Gram (-)ve bacteria levels (p<0.0001), and mean airborne inhalable (1->3)-b-D-glucan and fungi levels (p=0.0003). The correlations between mean respirable endotoxin levels vs Gram (-)ve bacteria exposure levels (p=0.005), and respirable (1->3)-b-D-glucan exposure levels vs total fungi levels (p=0.005) were also significant. Significant correlations were found between lung function and personal exposures. Multivariate analyses showed that the effect of all the personal exposures on cross-shift decrements in lung function was more prominent among sawmill and chip mill workers compared with joinery workers. Woodworkers had markedly high prevalence of cough, phlegm, chronic bronchitis, frequent headaches, throat and eye irritations, and nasal symptoms compared with controls. Among the woodworkers, smokers had a high prevalence of chronic bronchitis (20%) compared with non-smokers (10%). Some workers also reported a variety of allergy problems due to exposure to various types of wood dust. Both joinery workers and sawmill and chip mill workers revealed significant correlations between work-related symptoms and personal exposures. Chronic bronchitis was significantly correlated with personal exposure to wood dust, endotoxin, (1->3)-b-D-glucan, fungi, and Gram (-)ve bacteria among joinery workers. Whereas among sawmill workers chronic bronchitis was significantly correlated with personal exposure to endotoxin, (1->3)-b-D-glucan, and fungi. Woodworkers showed significant positive correlations between percentage cross-shift change (decrease) in lung function and respiratory symptoms. Significant inverse correlations were also found among percentage predicted lung function and respiratory symptoms. The elevated inhalable dust exposures observed in this study can be explained by a combination of factors, including: lack of awareness of potential health effects of wood dust exposure among both management and workers, aging equipment, inadequate and ineffective dust extraction systems or usually none especially for hand held tools, poor maintenance of the ventilation system in some, non-segregation of dusty processes, dry sweeping, and the use of compressed air jets. The determinant-of-exposure analysis confirmed the field observations. The significant determinants of personal inhalable dust exposures (n=163) were found to be: local exhaust ventilation, job title, use of hand-held tools, cleaning method used, use of compressed air, and green or dry wood processed. Type of wood processed was not found to be statistically significant. A majority of workers (~90%) did not wear appropriate respirators approved for wood dust, while the workers who did wear them, used them on average less than 50% of the time. Workers should be protected by controlling dust at its source. When exposure to wood dust cannot be avoided, engineering controls should be supplemented with the use of appropriate personal protective equipment.

<p>Since 1986 patients with ocular malignant melanoma have been treated with Ru-106 plaques at S:t Erik Eye Hospital. In 1998 I-125 radioactive seed plaques was presented as an alternative to Ru-106 when treating tumors with an apical height greater than 7 mm. Until June 2005 the doseplanning of these plaques was based on a depth-dose curve made in the dose planning system Cadplan supplied by Varian Medical Systems. In the recent years the capabilities of computerized 3D dose planning system has increased greatly. The number of types of seeds on the market has also increased.</p><p>In order to implement the modern 3D dose planning system Brachy Vision 7.3.10 in planning the I-125 plaques, a review of the dose planning process have been done.</p><p>The ultra sound equipment used by the ophthalmologist to determine the apical height of the tumor has been investigated in terms of accuracy. A phantom has been developed for this task.</p><p>As new seeds entered the market a comparision have been made comparing the Amersham 6711 seed with the Bebig I25.S06 seed. A method for measuring the activity of the single seeds has also been developed.</p><p>The dose planning system Brachy Vision 7.3.10 have been compared to the old dose planning method, and an implementation of the plaques into Brachy Vision have been made.</p><p>The ultra sound equipment was accurate in the regions of interest. It was also discovered that the Bebig I25.S06 seed gave slightly higher dose compared to the Amersham 6711 with the same activity. The difference between the seeds is however small. The results indicate that the old dose planning method gave a slight underdosage.</p>

<p>The present thesis is focused on the development and application of dose response models for radiation therapy. Radiobiological models of tissue response to radiation are an integral part of the radiotherapeutic process and a powerful tool to optimize tumor control and minimize damage to healthy tissues for use in clinical trials. Ideally, the models could work as a historical control arm of a clinical trial eliminating the need to randomize patents to suboptimal therapies. In the thesis overview part, some of the basic properties of the dose response relation are reviewed and the most common radiobiological dose-response models are compared with regard to their ability to describe experimental dose response data for rat spinal cord using the maximum likelihood method. For vascular damage the relative seriality model was clearly superior to the other models, whereas for white matter necrosis all models were quite good except possibly the inverse tumor and critical element models. The radiation sensitivity, seriality and steepness of the dose-response relation of the spinal cord is found to vary considerably along its length. The cervical region is more radiation sensitive, more parallel, expressing much steeper dose-response relation and more volume dependent probability of inducing radiation myelitis than the thoracic part. The higher number of functional subunits (FSUs) consistent with a higher amount of white matter close to the brain may be responsible for these phenomena. With strongly heterogeneous dose delivery and due to the random location of FSUs, the effective size of the FSU and the mean dose deposited in it are of key importance and the radiation sensitivity distribution of the FSU may be an even better descriptor for the response of the organ. An individual optimization of a radiation treatment has the potential to increase the therapeutic window and improve cure for a subgroup of patients.</p>

<p>Patient dose in diagnostic radiology is usually expressed in terms of organ dose and effective dose. The latter is used as a measure of the stochastic risk. Determinations of these doses are obtained by measurements (Thermoluminescent dosemeters) or by calculations (Monte Carlo simulation).</p><p>Conversion factors for the calculation of effective dose from dose-area product (DAP) values are commonly used to determine radiation dose in conventional x-ray imaging to realize radiation risks for different investigations, and for different ages. The exposure can easily be estimated by converting the DAP into an effective dose.</p><p>The aim of this study is to determine the conversion factor in procedures by computing the ratio between effective dose and DAP for fluoroscopic cardiac procedures in adults and for conventional lung and urography examinations in children.</p><p>Thermoluminescent dosemeters (TLD) were placed in an anthropomorphic phantom (Alderson Rando phantom) and child phantom (one year old) in order to measure the organ dose and compute the effective dose. A DAP meter was used to measure dose-area product.</p><p>MC calculations of radiation transport in mathematical anthropomorphic phantoms were used to obtain the effective dose for the same conditions with DAP as input data.</p><p>The deviation between the measured and calculated data was less than 10 %. The conversion factor for cardiac procedures varies between 0.19 mSvGy-1 cm-2 and 0.18 mSvGy-1 cm-2, for TLD respective MC. For paediatric simulation of a one year old phantom the average conversion factor for urography was 1.34 mSvGy-1 cm-2 and 1,48 mSvGy-1cm-2 for TLD respective MC. This conversion factor will decrease to 1.07 mSvGy-1 cm-2 using the TLD method, if the new ICRP (ICRP Publication 103) weighting factors were used to calculate the effective dose.</p><p>For lung investigations, the conversion factor for children was 1.75 mSvGy-1 cm-2 using TLD, while this value was 1.62 mSvGy-1 cm-2 using MC simulation. The conversion value increased to 2.02 mSvGy-1 cm-2 using ICRP’s new recommendation for tissue weighting factors and child phantom.</p>

Current protection of the marine environment from radiation is based largely on measuring, estimating and modelling accumulation and impact(s) of radionuclides in a few marine species. Using a relevant marine organism, this thesis focusses on investigating some poorly described phenomena that could cause deviations from predicted measurements. Paper I investigated the biological transformation of tritium (radioactive hydrogen) into an organic compound. The resulting organically bound tritium (OBT) showed increased accumulation in mussels, unique incorporation into a key biological molecule (DNA), extended persistence in tissues, and greater toxicity than the inorganic form. Paper II demonstrated significant disparity in OBT accumulation between functionally similar microalgae species and that OBT in algae is readily transferred to a consumer. Highly radioactive particles are a complex issue in radioecology due to their concentrated dose geometry, potentially inducing very different impacts in organisms, compared to external irradiation. Paper III developed a method to introduce radioactive particles that would facilitate their recovery, improve dose-calculation, and aid the measurement of toxicological endpoints. It also showed that such particles can be incorporated into mussel tissues, causing significant effects. In Paper IV, hypoxia – another major ecological hazard in the marine environment – was expected to reduce radiosensitivity. The minimal observable effect from radiation prevented identification of such an interaction, and indicates drawbacks in the (otherwise sensitive) endpoints used. It appears that stressors like hypoxia may be more of a health hazard to marine organisms than environmental levels of ionising radiation. By understanding such causes of variation in accumulation and impact, it is possible to improve risk assessment, providing more justification for regulations chosen and minimising conservatism in setting environmental standards. / <p>At the time of doctoral defense, the following papers were not published and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>

The electrochemical treatment (EChT) of tumours entails thattumour tissue is treated with a continuous direct currentthrough two or more electrodes placed in or near the tumour.Promising results have been reported from clinical trials inChina, where more than ten thousand patients have been treatedwith EChT during the past ten years. Before clinical trials canbe conducted outside of China, the underlying destructionmechanism behind EChT must be clarified and a reliabledose-planning strategy has to be developed. One approach inachieving this is through mathematical modelling. Mathematical models, describing the physicochemical reactionand transport processes of species dissolved in tissuesurrounding platinum anodes and cathodes, during EChT, aredeveloped and visualised in this thesis. The consideredelectrochemical reactions are oxygen and chlorine evolution, atthe anode, and hydrogen evolution at the cathode. Concentrationprofiles of substances dissolved in tissue, and the potentialprofile within the tissue itself, are simulated as functions oftime. In addition to the modelling work, the thesis includes anexperimental EChT study on healthy mammary tissue in rats. Theresults from the experimental study enable an investigation ofthe validity of the mathematical models, as well as of theirapplicability for dose planning. The studies presented in this thesis have given a strongindication of the destruction mechanism involved in EChT. It isshown by the modelling work, in combination with theexperiments, that the most probable cause of tissue destructionis acidification at the anode and alkalisation at the cathode.The pH profiles obtained from the theoretical models have showngood correlation with the experimentally measured destructionzones, assuming that a pH above and below certain values causetissue destruction. This implies that the models presented inthis thesis could be of use in predicting the tumourdestruction produced through EChT, and thereby provide a basisfor a systematic dose planning of clinical treatments.Moreover, the models can serve as valuable tools in optimisingthe operating conditions of EChT. Modelling work of theanode processes has explained the roleof chlorine in the underlying destruction mechanism behindEChT. It is found that the reactions of chlorine with tissueplay important roles as generators of hydrogen ions. Thecontribution of these reactions to the acidification of tissue,surrounding the anode, is strongly dependent on the appliedcurrent density and increases with decreasing currentdensity. <b>Keywords:</b>cancer, direct current, dose planning,electrochemical treatment (EChT), electrotherapy, mathematicalmodelling, tumour.

Threats from man-made radionuclides include waste issues, increasing number of power plants, underground bomb testing, nuclear weapons, and “dirty bombs”. Until recently the ionizing radiation protection system focused on protecting humans with an implied protection of biota. However, goals of sustainable development and precautionary principles for human activity are leading to an inclusion of plant and animal populations in the protection system. From this perspective, the present thesis examines wetlands that function as sinks for the radionuclide 137Cs, and describes calculated and measured radiation doses to residing biota. Also, multi-level effects from exposure to low-dose rate ionizing radiation were studied. Accumulation of 137Cs after the Chernobyl accident fallout was studied in a riparian wetland with a mean activity concentration of 1 200 kBq m-2 in Sweden (paper I). A mass balance budget of 137Cs showed that the sedimentation of new material was balanced by the decay process of 137Cs in parts of the wetland (paper I). Frogs were identified as organisms of concern in this wetland. Internal radiation doses, based on whole body measurements of frogs, were estimated to be lower than external doses based on soil samples (paper II). Current dose models for biota resulted in a wide range of doses depending on different levels of conservatism in the models. Therefore, in situ measurements with frog-phantoms were found to provide valuable dose information (paper III). Measured doses using frog-phantoms were lower than calculated doses using several dose models. Although a dose conversion factor by FASSET was found to be useful for comparison with measurements in the field. A higher dose was measured to the phantom surface in comparison to inner parts, i.e. the sensitive skin of frogs receives the highest dose. Estimated and measured radiation doses to frogs were below suggested dose rate limits. Low-dose rate 137Cs exposure of eggs and tadpoles from three amphibian species, Scaphiopus holbrookii, Bufo terrestris, and Rana catesbeiana, showed no increased levels of strand breaks in red blood cells, and no effects on development, survival or growth up to metamorphosis (paper IV). The ecological factor larval density had a stronger effect on metamorphic traits than low-dose rate radiation. Higher levels of strand breaks were detected after an acute dose in R. catesbeiana than after a chronic dose supporting a dose rate limit for protection of amphibians rather than a dose limit (paper IV). Based on current knowledge, frogs in the contaminated wetland are probably not exposed to radiation doses from 137Cs that are harmful for the population. However, variations in sensitivity between populations and species, and adaptive responses have been shown for amphibians exposed to other stressors. This supports further research on effects of chronic low-dose rates of ionizing radiation on amphibians.

The present thesis is focused on the development and application of dose response models for radiation therapy. Radiobiological models of tissue response to radiation are an integral part of the radiotherapeutic process and a powerful tool to optimize tumor control and minimize damage to healthy tissues for use in clinical trials. Ideally, the models could work as a historical control arm of a clinical trial eliminating the need to randomize patents to suboptimal therapies. In the thesis overview part, some of the basic properties of the dose response relation are reviewed and the most common radiobiological dose-response models are compared with regard to their ability to describe experimental dose response data for rat spinal cord using the maximum likelihood method. For vascular damage the relative seriality model was clearly superior to the other models, whereas for white matter necrosis all models were quite good except possibly the inverse tumor and critical element models. The radiation sensitivity, seriality and steepness of the dose-response relation of the spinal cord is found to vary considerably along its length. The cervical region is more radiation sensitive, more parallel, expressing much steeper dose-response relation and more volume dependent probability of inducing radiation myelitis than the thoracic part. The higher number of functional subunits (FSUs) consistent with a higher amount of white matter close to the brain may be responsible for these phenomena. With strongly heterogeneous dose delivery and due to the random location of FSUs, the effective size of the FSU and the mean dose deposited in it are of key importance and the radiation sensitivity distribution of the FSU may be an even better descriptor for the response of the organ. An individual optimization of a radiation treatment has the potential to increase the therapeutic window and improve cure for a subgroup of patients.

Since 1986 patients with ocular malignant melanoma have been treated with Ru-106 plaques at S:t Erik Eye Hospital. In 1998 I-125 radioactive seed plaques was presented as an alternative to Ru-106 when treating tumors with an apical height greater than 7 mm. Until June 2005 the doseplanning of these plaques was based on a depth-dose curve made in the dose planning system Cadplan supplied by Varian Medical Systems. In the recent years the capabilities of computerized 3D dose planning system has increased greatly. The number of types of seeds on the market has also increased. In order to implement the modern 3D dose planning system Brachy Vision 7.3.10 in planning the I-125 plaques, a review of the dose planning process have been done. The ultra sound equipment used by the ophthalmologist to determine the apical height of the tumor has been investigated in terms of accuracy. A phantom has been developed for this task. As new seeds entered the market a comparision have been made comparing the Amersham 6711 seed with the Bebig I25.S06 seed. A method for measuring the activity of the single seeds has also been developed. The dose planning system Brachy Vision 7.3.10 have been compared to the old dose planning method, and an implementation of the plaques into Brachy Vision have been made. The ultra sound equipment was accurate in the regions of interest. It was also discovered that the Bebig I25.S06 seed gave slightly higher dose compared to the Amersham 6711 with the same activity. The difference between the seeds is however small. The results indicate that the old dose planning method gave a slight underdosage.

Xylitol, classified as a natural sugar substitute, has for about 35 years been known as an agent that may act against caries. The mechanism of action; how it inhibits mutans streptococci (MS) and the clinical dose-response relationship are not however fully investigated. The general aim of the investigations was to evaluate the effect of xylitol on oral ecology in children and adolescents. A series of experimental and controlled clinical trials were performed in which samples of saliva and plaque was collected and analysed with respect to xylitol content, pH, microbial composition and lactic acid production. In paper I, significantly reduced proportions of xylitol-sensitive MS in saliva were demonstrated after 18 weeks of regular use of two dose regimens of xylitol-containing tablets (1.7g and 3.4g xylitol/day) but the acidogenicity in dental plaque was not affected. In paper II, the effect on interdental plaque-pH of two different single dose intakes (2.0g and 6.0g) of xylitol was evaluated. The higher xylitol dose counteracted the pH-drop significantly (p&lt;0.05) when the chewing was followed by a sucrose rinse while the lower dose did not differ from the control. In paper III, the xylitol concentrations in saliva after use of different common xylitol-containing products (0.1g-1.3g) were investigated. Statistically significant elevations of salivary xylitol levels were demonstrated for all products during the first 8-16 min when compared with baseline (p&lt;0.05) but the individual variation was considerable. In samples of supragingival dental plaque, a high dose rinse (6.0g) increased the xylitol concentrations for a longer period (&gt;30 min) than a low dose rinse (2.0g). In paper IV, it was demonstrated that 6.0g of xylitol in chewing gums, every day in 4 weeks, gave significantly less visible plaque and a significantly reduced sucrose-induced lactic acid formation (p&lt;0.05) in saliva. Furthermore, the proportion of MS decreased significantly (p&lt;0.05) compared to baseline. In paper V, the salivary uptake of [14C]-xylitol was compared with a specific assay determining xylitol-sensitive MS and a fair positive correlation (p&lt;0.05) between the two assays was found. In a controlled trial, the proportions of MS and the salivary xylitol uptake decreased significantly (p&lt;0.05) in the xylitol gum test group after 4 weeks compared to baseline which was in contrast to the control gum group. No serious adverse effects were reported in any of the investigations. The main conclusions from this thesis were: a) various xylitol-containing products increased the xylitol levels in saliva and plaque, b) 6.0g of xylitol could counteract the interdental pH-drop after sugar consumption and reduce lactic acid formation in saliva c) a daily dose of 6.0g xylitol reduced the amount of visible plaque and altered the salivary microbial composition, d) a transient shift of MS strains in saliva was demonstrated during periods of regular intake of xylitol products but no long-term impact was found after its termination. The relatively high amount of xylitol needed for a beneficial effect on the oral ecology calls for a further development of effective and safe routes for administration.