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Purpose: To present details of the recent version of the 'Local Effect Model' (LEM), that has been developed and implemented in treatment planning for the ion beam therapy pilot project performed at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany., Materials and Methods: The new version of the model is based on a detailed consideration of the spatial distribution of the initial damages, i.e., double-strand breaks (DSB). This spatial distribution of DSB is obtained from the radial dose profile of the ion track using Monte Carlo methods. These distributions are then analyzed with regard to the proximity of DSB. This version of the model also facilitates the calculation of full dose response curves up to arbitrary high doses, thus allowing to thoroughly check the approximations previously used to estimate the quadratic term (β-term) for the linear-quadratic description of dose response curves., Results: The accuracy of the model predictions is demonstrated by good agreement of the relative biological effectiveness (RBE) as a function of the linear energy transfer (LET) with experimental data obtained for V79 cells after carbon irradiation. The β-values predicted by the full simulation tend to be larger as compared to the approximation in the intermediate LET range., Conclusion: The new version of the model allows a more mechanistic description of the biological effects of ion radiation. The full simulation is a prerequisite for tests of the validity of the approach at high doses, which are of particular interest for application in hypofractionation studies.

Unlabelled: PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center., Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility., Results: In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms., Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Treatment of surgically unresectable recurrence in the head and neck region remains a therapeutic problem with the only curative option being a second course of radiation with a tumouricidal dose. We report initial toxicity and efficacy of charged particle therapy in this situation., Methods: Treatment-related side-effects of patients treated with charged particle beams for recurrent tumours of the head and neck were prospectively collected and patient data was retrospectively analysed with regard to toxicity and efficacy of the treatment according to CTCAE v. 4.03 and RECIST., Results: Treatment was tolerated well without any severe acute toxicity. In non-chordoma/chondrosarcoma patients, overall response rate was 53.3% at 8 weeks post RT. 4/5 chordoma/chondrosarcoma patients showed no signs of further tumour progression., Conclusion: Initial experience of re-irradiation with scanned particle beams in recurrent tumours of the head and neck seems feasible and encouraging. Further follow-up is needed to investigate potential late effects., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: There is a need for safe and effective treatment options for irritable bowel syndrome (IBS). AST-120 (spherical carbon adsorbent) is a non-absorbed, carbon-based adsorbent with extensive adsorbing capability for histamine, serotonin and other substances implicated in IBS pathogenesis., Aim: To evaluate the efficacy and safety of AST-120 in non-constipating forms of IBS., Methods: This randomised, double-blind, placebo-controlled trial conducted in the US and Belgium enrolled 115 male and female patients fulfilling Rome III criteria for IBS; individuals with predominantly constipation symptoms were excluded. Subjects were randomised to AST-120 2 g tds or placebo for an 8-week double-blind treatment period, followed by a 2-week single-blind placebo washout and 8-week single-blind active treatment. The primary efficacy endpoint was the proportion of subjects achieving at least a 50% reduction in the number of days with abdominal pain compared with baseline., Results: At Week 4, 26.8% of subjects treated with AST-120 responded on the primary endpoint vs. 10.2% in the placebo arm (P=0.029); at Week 8 response rates were 32.1 and 25.4% respectively (NS). More AST-120 treated subjects experienced improvement in bloating and stool consistency. These benefits abated when AST-120 was replaced by placebo, and resumed once AST-120 was restarted. The frequency of adverse events with AST-120 were less than or equal to placebo., Conclusions: AST-120 is safe and well-tolerated and reduces pain and bloating in non-constipating IBS, although beneficial effects may be limited in duration. AST-120 represents a locally acting, non-absorbed, novel treatment for IBS and warrants further studies., (© 2011 Blackwell Publishing Ltd.)

Cytogenetic assay of the chromosomal apparatus of human blood lymphocytes was carried out after in vitro irradiation by heavy charged particles with high LET values. Blood plasm samples enriched with lymphocytes were irradiated by accelerated ions of carbon 12C (290 MeV/nucleon and LET = 70 keV/microm), neon 20Ne (400 MeV/nucleon and LET = 70 keV/microm), and iron 56Fe (500 MeV/nucleon and LET = 200 keV/microm) in the dose range from 0.25 to 1 Gy. Rate of chromosome aberrations showed a linear dependence on doses from the densely ionizing radiations with high LET values. Frequency of dicentrics and centric rings in human lymphocytes irradiated by 12C with the energy of 290 MeV/nucleon was maximal at 1 Gy (p < 0.05) relative to the other heavy particles. It was found that relative biological effectiveness of heavy nuclei is several times higher than of 60Co gamma-radiation throughout the range of doses in this investigation.

Our work aims to understand the effects of shielding on the induction of biological damage by heavy charged particles and to compare the shielding effects of different materials at the same LET from two aspects: the biological effectiveness including or not including secondary particles emitted at large angles and the biological effectiveness at different angles with respect to the beam direction. We designed and conducted biological experiments to determine the biological effectiveness of 200 MeV/u carbon ions after traversing different shielding materials (Lucite and aluminium). Whole blood samples, which were either attached to the shielding material (48 mm Lucite or 29 mm aluminium)or positioned at 300 cm away from it at different angles with respect to the beam axis, were exposed to carbon ion beams. For comparison, whole blood samples were exposed directly to 200 MeV/u carbon ions. Chromosomal aberrations in lymphocytes were scored. The results indicated that the biological effectiveness per unit dose was not significantly changed by 48 mm Lucite or 29 mm aluminium, and no significant differences were observed in lymphocytes attached to the target and in lymphocytes positioned at a distance of 300 cm away from the target, at 0º angle of the beam axis. However, when plotted as a function of the number of ions hitting the shielding target, the curves are separated and the shield increases the effectiveness per unit ion. The frequency of chromosomal aberrations at tilted angles behind 29 mm Al and 48 mm Lucite was almost the same. These lesions were considered to be caused by secondary particles due to the passage of particles through the shielding materials.

The characteristics and sources of organic carbon (OC) and elemental carbon (EC) in PM(2.5) in 2006-2007 as well as their impact on the formation of heavy haze in Shanghai were investigated. Daily average concentrations of OC and EC ranged from 1.8 to 20.1 μg m(-3) and 0.5-7.8 μg m(-3) with averages of 7.2 and 2.8 μg m(-3), respectively. The carbonaceous aerosol (OC plus EC) contributed to ∼ 27.2% of the total mass of PM(2.5) on annual average. Obvious seasonal variation was observed in both OC and EC. The percentage of secondary organic carbon (SOC) contributed to OC was in a range of 2.4-66.8%, with an average of 40.1%. Three types of haze were classified based on their chemical composition. OC, EC, SO(2)/NO(2) (in turn, SO(4)(2-)/NO(3)(-)) were responsible for the formation of the three types of haze, respectively. The carbonaceous aerosol was one of the key factors in the formation of haze. Local emissions were the dominant sources of OC and EC in warm seasons, and long-range transport had a significant contribution to OC and EC in PM(2.5) in spring and winter in Shanghai., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The life cycle thinking was integrated with risk assessment to develop the life cycle risk assessment (LCRA) methodology in this study. Because LCRA assessed risks from a life cycle perspective of the concerned policies, it was helpful to identify important sources, contaminants, receptors and exposure pathways along the life cycle of reuse activities. The case study showed that different reuse scenarios resulted in risk shift between different life stages and receptors, and using duration of pavement was an essential factor for risk management. When ash reuse strategies were made based on a focus on the stage of reuse, the rank of strategies were shown to be different from the one based on the total population risks over the entire life cycle. This demonstrated the importance of decision criteria used in selecting reuse strategies. The results also showed that when bottom ash was reused, the health risk was shifted to the laborers; the individual risks of laborers were higher than residents through exposure to Cr and Cd via inhalation and dermal contact. Although the population risk at the treatment stage was the highest, the smaller size of exposed population would make it quite effective to reduce the risk of the laborers., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Little is known about exposure control strategies currently being implemented to minimize exposures during the production or use of nanomaterials in the United States. Our goal was to estimate types and quantities of materials used and factors related to workplace exposure reductions among companies manufacturing or using engineered carbonaceous nanomaterials (ECNs)., Methods: Information was collected through phone surveys on work practices and exposure control strategies from 30 participating producers and users of ECN. The participants were classified into three groups for further examination., Results: We report here the use of exposure control strategies. Observed patterns suggest that large-scale manufacturers report greater use of nanospecific exposure control strategies particularly for respiratory protection., Conclusion: Workplaces producing or using ECN generally report using engineering and administrative controls as well as personal protective equipment to control workplace employee exposure.

Background: The advent of fishing rods made of carbon fiber and graphite rods has greatly increased the risks of electrical injuries associated with fishing. The braided fishing lines and metal hooks put the fishermen at risk for electrical injuries., Purpose: We review our burn center's experience with electrical injuries related to fishing activities during the last four years., Patients and Method: We retrospectively collected data on patients with electrical burns related to fishing activities between January 2006, when our burns unit was established, and December 2009. Eight patients with electrical burns were admitted during this period of time, five who sustained the injury while fishing, due to contact of the fishing rod with overhead high-voltage cables and three who were injured during illegal fishing, using electricity to stun the fish., Results: The total burn surface area ranged from 0.5% to 70%. Three of the patients sustained fourth degree burns, while the rest had second and third degree burns. One patient underwent scapulohumeral disarticulation and an above-knee amputation. Two patients had fingers and toes amputated. Latissimus dorsi and anterolateral thigh flaps were used to cover the defects in two cases. Local flaps were employed in other two cases to cover the tissue defects. Two patients died., Conclusion: Fishing-related burns and illegal fishing can lead to serious injuries and death., (Copyright © 2010 Elsevier Ltd and ISBI. All rights reserved.)

Oil fly ash (OFA), containing high amounts of transition metals, is among the most reactive airborne particulate matter emissions, which have been associated with several diseases, such as chronic obstructive pulmonary diseases (COPD), lung cancer, and cardiovascular diseases. The aim of the present study was to evaluate mitochondrial alterations in OFA-exposed cultured pneumocytes and in their progeny. Alveolar epithelial cells (A549 line) were exposed either to an OFA water solution, containing 68.8 μM vanadium (V), 110.4 μM iron (Fe), and 18.0 μM nickel (Ni), or to the individual metal solutions. Structural and functional mitochondrial parameters were determined in exposed cultures and in 3 consecutive subcultures. OFA, V and Fe solutions caused a time-dependent loss of mitochondrial enzymatic activity, glutathione depletion, generation of lipid hydroperoxides, hydrogen peroxide and other reactive oxygen species, especially in G(0)-G(1) phase cells, accompanied by a decrease in mitochondrial mass and transmembrane potential. Mitochondrial alterations were partly transmissible to daughter cells for up to 3 generations. Fe and especially V were responsible for the observed mitochondrial alterations in pneumocytes exposed to OFA. Spread of mitochondrial dysfunctions to daughter cells is expected to amplify oxidative stress in the respiratory epithelium and to play an important role in the pathogenesis of respiratory diseases., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Purpose: To study the relative biological effectiveness (RBE) of carbon ion beams relative to X-rays for local tumor control in a syngeneic rat prostate tumor (Dunning subline R3327-AT1)., Methods and Materials: A total of 198 animals with tumors in the distal thigh were treated with increasing single and split doses of either (12)C ions or photons using a 20-mm spread-out Bragg peak. Endpoints of the study were local control (no tumor recurrence within 300 days) and volumetric changes after irradiation. The resulting values for D(50) (dose at 50% tumor control probability) were used to determine RBE values., Results: The D(50) values for single doses were 32.9 ± 0.9 Gy for (12)C ions and 75.7 ± 1.6 Gy for photons. The respective values for split doses were 38.0 ± 2.3 Gy and 90.6 ± 2.3 Gy. The corresponding RBE values were 2.30 ± 0.08 for single and 2.38 ± 0.16 for split doses. The most prominent side effects were dry and moist desquamation of the skin, which disappeared within weeks., Conclusion: The study confirmed the effectiveness of carbon ion therapy for severely radioresistant tumors. For 1- and 2-fraction photon and (12)C ion radiation, we have established individual D(50) values for local tumor control as well as related RBE values., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The article covers results of clinical and roentgenologic data analysis. The data were obtained in the study that covered 447 pneumoconiosis patients, 75 of which were subjected to high resolution CT. If compared to chest X-ray, high resolution CT helps more precise forecast of further course in pneumoconiosis.

Inhalation of carbon nanoparticles (CNP) from toner dust has been shown to have impact on the respiratory health of persons exposed. Office printers are known emitters of CNP. We report about a female open office worker who developed weight loss and diarrhoea. Laparoscopy done for suspected endometriosis surprisingly revealed black spots within the peritoneum. Submesothelial aggregates of CNP with a diameter of 31-67 nm were found by scanning and transmission electron microscopy in these tissue specimens. Colon biopsies showed inflammatory bowel disease with typically signs of Crohn disease, but no dust deposits. Transport of CNP via lymphatic and blood vessels after inhalation in the lungs has to be assumed. In this case respiratory symptoms were not reported, therefore no lung function tests were done. We have shown that workers with toner dust exposure from laser printers can develop submesothelial deposition of CNP in the peritoneum. Impact of toner dust exposure on the respiratory health of office workers, as suspected in other studies, has to be evaluated further.

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst-case biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices., (© 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Three cases, including one case report and two clinical images, have been reported of extraintestinal or peritoneal black maculae detected at laparoscopy after colonoscopic tattooing, presumably from intraperitoneal spillage of India ink during tattooing., Aims: Report three cases of inadvertent extraintestinal tattooing from endoscopic tattooing of intestinal lesions, provide histologic evidence for the presumed pathophysiology, and promulgate recommendations to prevent this complication., Methods: Three patients underwent endoscopic tattooing of intestinal lesions using India ink, surgery for lesion removal, and pathologic analysis., Results: Three patients had black macular patches or streaks identified intraoperatively at extraintestinal sites after endoscopic tattooing of intestinal lesions with India ink: (1) black patches on peritoneum 7 days after colonoscopic tattooing of cecal cancer, (2) black streaks on band connecting cecum to peritoneum 13 days after colonoscopic tattooing of cecal cancer, and (3) blackish band on jejunal mesentery 28 days after tattooing presumptive bleeding jejunal lesion. Pigmentation was detected at both injection and extraintestinal sites in all patients by (1) surgery, (2) gross pathology, and (3) microscopic examination demonstrating intracellular black pigmentation within mesothelial cells and macrophages. Special histologic stains were consistent with a carbon-based pigment, and inconsistent with iron or melanin as the pigment. The proposed mechanism is intraperitoneal India ink spillage from deep intestinal injection, as supported by histologic findings of subserosal pigment accumulation. An alternative histologic mechanism is migration of pigment-laden macrophages via lymphovascular channels., Conclusions: Endoscopic injection of India ink using standard sclerotherapy needles can inadvertently tattoo extraintestinal sites in addition to tattooing the primary lesion. Despite its striking appearance, this intraoperative, gross, and microscopic finding is likely not pathologically significant, given its proposed pathophysiology. Surgical recognition of this entity is important, however, to prevent misinterpretation of findings as peritoneal melanoma, endometrial implants, infarcted mesentery, or tattooed cancer. This complication may be prevented by proper tattooing technique.

Summary Background: The translocation of nanoparticles in the lung toward effector organs via the circulation is considered an important direct pathway for systemic effects of nanoparticles after inhalation. Recently, we have reported that a moderate dose of systemically administered nanosized carbon black particles exerted thrombogenic effects in hepatic microvessels of healthy mice., Objectives: This study addresses the questions of whether similar thrombogenic effects are also evoked upon inhalation of nanosized carbon particles (NCP) and whether NCP-induced hepatic platelet accumulation is associated with pulmonary or systemic inflammation., Methods: Two and 8 h after a 24-h exposure to either filtered air or to NCP, intravital fluorescence microscopy of the hepatic microcirculation was performed in C57Bl/6 mice. Parameters of pulmonary or systemic inflammatory response were determined in bronchoalveolar lavage and blood/plasma samples., Results: Inhalative exposure to NCP caused platelet accumulation in the hepatic microvasculature, whereas leukocyte recruitment and sinusoidal perfusion did not differ from controls. Fibrinogen deposition was detected by immunohistochemistry in both hepatic and cardiac microvessels from NCP-exposed mice. In contrast, inhalation of NCP affected neither the plasma levels of proinflammatory cytokines nor blood cell counts. Moreover, the bronchoalveolar lavage data indicate that no significant inflammatory response occurred in the lung., Conclusions: Thus, exposure to NCP exerts thrombogenic effects in the microcirculation of healthy mice independent of the route of administration (i.e. inhalation or systemic intra-arterial administration). The NCP-induced thrombogenic effects are not liver specific, are associated with neither a local nor a systemic inflammatory response, and seem to be independent of pulmonary inflammation.

Objective: We examined whether more precise exposure measures would better detect associations between traffic-related pollution, elemental carbon (EC), nitrogen dioxide (NO2), and heart rate variability (HRV)., Methods: Repeated 24-hour personal and ambient PM2.5, EC, and NO2 were measured for 30 people living in Atlanta, GA. The association between HRV and either ambient concentrations or personal exposures was examined using linear mixed effects models., Results: Ambient PM2.5, EC, NO2, and personal PM2.5 were not associated with HRV. Personal EC and NO2 measured 24 hours before HRV were associated with decreased RMSSD, PNN50, and HF and with increased LF/HF. RMSSD decreased by 10.97% (95% confidence interval: -18.00 to -3.34) for an inter-quartile range change in personal EC (0.81 microg/m3)., Conclusions: Results indicate decreased vagal tone in response to traffic pollutants, which can best be detected with precise personal exposure measures.

In large epidemiological studies, many researchers use surrogates of air pollution exposure such as geographic information system (GIS)-based characterizations of traffic or simple housing characteristics. It is important to evaluate quantitatively these surrogates against measured pollutant concentrations to determine how their use affects the interpretation of epidemiological study results. In this study, we quantified the implications of using exposure models derived from validation studies, and other alternative surrogate models with varying amounts of measurement error on epidemiological study findings. We compared previously developed multiple regression models characterizing residential indoor nitrogen dioxide (NO(2)), fine particulate matter (PM(2.5)), and elemental carbon (EC) concentrations to models with less explanatory power that may be applied in the absence of validation studies. We constructed a hypothetical epidemiological study, under a range of odds ratios, and determined the bias and uncertainty caused by the use of various exposure models predicting residential indoor exposure levels. Our simulations illustrated that exposure models with fairly modest R(2) (0.3 to 0.4 for the previously developed multiple regression models for PM(2.5) and NO(2)) yielded substantial improvements in epidemiological study performance, relative to the application of regression models created in the absence of validation studies or poorer-performing validation study models (e.g., EC). In many studies, models based on validation data may not be possible, so it may be necessary to use a surrogate model with more measurement error. This analysis provides a technique to quantify the implications of applying various exposure models with different degrees of measurement error in epidemiological research.

Carbon soot is produced in the process of diamond manufacture. Recent experimental and epidemiological studies have associated exposure to carbon nanoparticles with effects on cardiovascular system and blood cells. The objective of this study is to assess the cardiovascular effects consequent to chronic respiratory exposure of carbon soot. A cross-sectional occupational health survey was conducted in all consenting workers who employed in the production wing of diamond-processing industries. Blood pressure, ECGs, height, weight, and blood counts were measured and evaluated. Blood pressure measurements revealed a high prevalence of hypertension in young workers. Left atrial abnormality (LAA) was the major finding in the electrocardiograms. We found a high prevalence of hypertension in young diamond workers. The LASER saw operators had highest prevalence of LAA. White cell count and prevalence of hypertension was highest for the workers in grinder operations.

Rationale: The effects of exposure to specific components of ambient fine particulate matter (PM(2.5)), including metals and elemental carbon (EC), have not been fully characterized in young children., Objectives: To compare temporal associations among PM(2.5); individual metal constituents of ambient PM(2.5), including nickel (Ni), vanadium (V), and zinc (Zn); and EC and longitudinal reports of respiratory symptoms through 24 months of age., Methods: Study participants were selected from the Columbia Center for Children's Environmental Health birth cohort recruited in New York City between 1998 and 2006. Respiratory symptom data were collected by questionnaire every 3 months through 24 months of age. Ambient pollutant data were obtained from state-operated stationary monitoring sites located within the study area. For each subject, 3-month average inverse-distance weighted concentrations of Ni, V, Zn, EC, and PM(2.5) were calculated for each symptom-reporting period based on the questionnaire date and the preceding 3 months. Associations between pollutants and symptoms were characterized using generalized additive mixed effects models, adjusting for sex, ethnicity, environmental tobacco smoke exposure, and calendar time., Measurements and Main Results: Increases in ambient Ni and V concentrations were associated significantly with increased probability of wheeze. Increases in EC were associated significantly with cough during the cold/flu season. Total PM(2.5) was not associated with wheeze or cough., Conclusions: These results suggest that exposure to ambient metals and EC from heating oil and/or traffic at levels characteristic of urban environments may be associated with respiratory symptoms among very young children.

Burns from seemingly innocuous substances are rare, probably underrecognized and typically present late. We describe a case of a child who sustained a full-thickness burn after an application of a coal ash poultice for ankle pain. This case report highlights a rare cause of a chemical burn that may become more common with increasing use of traditional remedies worldwide.

The threat to human health from climate change means that all levels of government and private and public agencies will need to change their current practices to reduce carbon emissions. The health sector will also need to respond and change practice. The National Health Service in the United Kingdom is developing a systematic and strategic approach to reduce its carbon footprint, as described in the recently released NHS Carbon Reduction Strategy for England. The work is being led by the Service's new Sustainable Development Unit. While the Australian health care system has not yet embraced a shared vision for carbon reduction, there are examples emerging of how the sector is contributing to reduce greenhouse gas production. Examples from two NSW area health services to reduce energy use and promote active transport are presented. In both countries, these changes are supported by new legislation and policy.

Purpose: To assess the incidence of early delayed or late morbidity of the brain after particle therapy for skull base tumors and head-and-neck cancers., Methods and Materials: Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volume of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months., Results: Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between the brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses., Conclusion: Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between the brain lobes with and without RIBCs.

Fly-ash is a byproduct of the combustion of coal in power stations for the generation of electricity. The fly-ash forms from the melting of incombustible minerals found naturally in the coal. The very high coal combustion temperatures result in the formation of microscopic glass particles from which minerals such as quartz, haematite and mullite can later recrystallize. In addition to these minerals, the glassy fly-ash contains a number of leachable metals. Mullite is a well-known material in the ceramics industry and a known respiratory hazard. Macroscopically mullite can be found in a large range of morphologies; however microscopic crystals appear to favour a fibrous habit. Fly-ash is a recognized bioreactive material in rat lung, generating hydroxyl radicals, releasing iron, and causing DNA damage. However, the mechanisms of the bioreactivity are still unclear and the relative contributions of the minerals and leachable metals to that toxicity are not well known.

Background: Particulate air pollution has been consistently related to cardiovascular mortality. Some evidence suggests that particulate matter may accelerate the atherosclerotic process. Effects of within-city variations of particulate air pollution on survival after an acute cardiovascular event have been little explored., Methods: We conducted a cohort study of hospital survivors of acute myocardial infarction (MI) from the Worcester, MA, metropolitan area to investigate the long-term effects of within-city variation in traffic-related air pollution on mortality. The study builds on an ongoing community-wide investigation examining changes over time in MI incidence and case-fatality rates. We included confirmed cases of MI in 1995, 1997, 1999, 2001, and 2003. Long-term survival status was ascertained through 2005. A validated spatiotemporal land use regression model for traffic-related air pollution was developed and annual averages of elemental carbon at residence estimated. The effect of estimated elemental carbon on the long-term mortality of patients discharged after MI was analyzed using a Cox proportional hazards model, controlling for a variety of demographic, medical history, and clinical variables., Results: Of the 3895 patients with validated MI, 44% died during follow-up. Exposure to estimated elemental carbon in the year of entry into the study was 0.44 microg/m on average. All-cause mortality increased by 15% (95% confidence interval = 0.03%-29%) per interquartile range increase in estimated yearly elemental carbon (0.24 microg/m) after the second year of survival. No association between traffic-related pollution and all-cause mortality was observed during the first 2 years of follow-up., Conclusions: Chronic traffic-related particulate air pollution is associated with increased mortality in hospital survivors of acute MI after the second year of survival.

Objective: Laparoscopic surgery for colorectal cancer is now widespread. Small lesions in the colon can be difficult to palpate and with lack of tactile sensation, it is essential to accurately localize them preoperatively. This is a review article on current methods of tattooing including the use of different agents and associated complications. Aim To review current techniques in preoperative tumour localization and methods used for colonic tattooing including agents used, dosage and potential complications., Method: A literature search (Medline and Pubmed) was performed with manual cross referencing of all articles related to colonic tattooing., Results: Methods for localizing colonic tumours for laparoscopic resection include preoperative barium enema examination, CT colonography and intraoperative colonoscopy. The most effective method is, however, by tattooing with India ink performed endoscopically before surgery., Conclusion: India ink is a reliable method of marking tumour location within the colon as prelude to laparoscopic resection. Surgeons must, however, be aware of potential complications associated with this technique.

To determine the association between several elements of fine particulate air pollution (PM2.5) and mortality in a general population sample, daily time-series analysis was used to test the association between daily mortality and components of PM2.5 measured in downtown Santiago, Chile between 1998 and 2006. The strongest individual effect was seen for elemental carbon. A 5.28 ug/m3 increase in elemental carbon was associated with a relative risk (RR) of 1.08 (95% CI = 1.07-1.09) for total non-accidental mortality. Using factor analysis, a group of elements consistent with a mobile combustion source (carbon monoxide, nitrogen dioxide, elemental and organic carbon) was significantly associated with total mortality (RR 1.11; 95% CI = 1.083-1.138). Soil-sourced particles had a weaker but statistically significant mortality effect. Of the many sources of particulate air pollution, those from motor vehicle exhaust had the greatest observed effect on mortality.

Among particulate matter emissions from combustion processes, oil fly ash (OFA) displays a marked oxidative and inflammogenic reactivity, due to the high content of bioavailable transition metals. In the present study, we evaluated the biological effects of an OFA water solution, composed of the transition metals Fe (57.5%), V (32.4%), and Ni (10.1%), in human epithelial alveolar cells (A549 line). The fluorimetric analysis by 2',7'-dichlorofluorescein showed a significant, dose- and time-dependent induction of intracellular reactive oxygen species (ROS) triggered by OFA metal components at subtoxic doses. The metal chelator deferoxamine and the radical scavenger dimethylsulfoxide attenuated the metal-induced generation of ROS. Confocal microscopy observations strengthened these findings and showed an intense cytoplasmic fluorescence with perinuclear thickenings in A549 cells, in the absence of morphological damage. Metal-induced generation of ROS was significantly correlated with a dose- and time-dependent DNA damage, as assessed by single cell gel electrophoresis (comet assay). Catalase was able to decrease dramatically DNA damage. Fluorimetric analyses by diphenyl-1-pyrenylphosphine showed a parallelism between generation of ROS and formation of lipid peroxides. The results obtained in the experiments evaluating the effects of individual metal solutions did not show any significant difference in DNA damage between Fe(III) and V(IV), but highlighted the higher capability of V(IV) to increase ROS in the cytoplasmic compartment. The different behavior of these two elements, confirmed by the weak Fe-induced lipid peroxidation, may be ascribed to the presence of Fe-binding proteins, such as ferritin, in the cytoplasm. Finally, Ni(II) had negligible effects on ROS production. On the whole, the results obtained in this study show the strong capability of transition metals adsorbed to OFA to cause widespread damage to biological macromolecules, and suggest potential health effects resulting from exposure to power plant emissions in industrialized sites.

Purpose: The objective of this experiment was to compare the oncogenic potential of carbon ion beams and conventional photon beams for use in radiotherapy., Methods and Materials: The HeLa X human skin fibroblast cell line CGL1 was irradiated with carbon ions of three different energies (270, 100, and 11.4 MeV/u). Inactivation and transformation data were compared with those for 15 MeV photons., Results: Inactivation and transformation frequencies for the 270 MeV/u carbon ions were similar to those for 15-MeV photons. The maximal relative biologic effectiveness (RBE(alpha)) values for 100MeV/u and 11.4 MeV/u carbon ions, respectively, were as follows: inactivation, 1.6 +/- 0.2 and 6.7 +/- 0.7; and transformation per surviving cell, 2.5 +/- 0.6 and 12 +/- 3. The curve for dose-transformation per cell at risk exhibited a maximum that was shifted toward lower doses at lower energies., Conclusions: Transformation induction per cell at risk for carbon ions in the entrance channel was comparable to that for photons, whereas for the lower energies, 100 MeV/u and 11 MeV/u, which are representative of the energies delivered to the tumor margins and volume, respectively, the probability of transformation in a single cell was greater than it was for photons. In addition, at isoeffective doses with respect to cell killing, the 11.4-MeV/u beam was more oncogenic than were photons.

The mechanisms underlying the association between air pollution and cardiovascular morbidity and mortality are unknown. This study aimed to determine whether controlled exposure to elemental carbon ultrafine particles (UFP) affects electrocardiogram (ECG) parameters describing heart rate variability; repolarization duration, morphology, and variability; and changes in the ST segment. Two separate controlled studies (12 subjects each) were performed using a crossover design, in which each subject was exposed to filtered air and carbon UFP for 2 hours. The first protocol involved 2 exposures to air and 10 microg/m(3) (approximately 2 x 10(6) particles/cm(3), count median diameter approximately 25 nm, geometric standard deviation approximately 1.6), at rest. The second protocol included 3 exposures to air, 10, and 25 microg/m(3) UFP (approximately 7 x 10(6) particles/cm(3)), with repeated exercise. Each subject underwent a continuous digital 12-lead ECG Holter recording to analyze the above ECG parameters. Repeated measures analysis of variance (ANOVA) was used to compare tested parameters between exposures. The observed responses to UFP exposure were small and generally not significant, although there were trends indicating an increase in parasympathetic tone, which is most likely also responsible for trends toward ST elevation, blunted QTc shortening, and increased variability of T-wave complexity after exposure to UFP. Recovery from exercise showed a blunted response of the parasympathetic system after exposure to UFP in comparison to air exposure. In conclusion, transient exposure to 10-25 microg/m(3) ultrafine carbon particles does not cause marked changes in ECG-derived parameters in young healthy subjects. However, trends are observed indicating that some subjects might be susceptible to air pollution, with a response involving autonomic modulation of the heart and repolarization of the ventricular myocardium.

Previous studies have demonstrated an association between air pollution and asthma exacerbation. Less understood is the effect of elemental carbon (EC), and the interaction of EC with temperature, on increases in pediatric asthma emergency department visits and how these relationships change across the seasons in a metropolitan area with several industries and relatively low air pollution. Measurements of EC, ozone (O(3)), sulfur dioxide (SO(2)), and total oxides of nitrogen (NO(x)) were available from the St. Louis EPA Supersite for June 1, 2001 to May 31, 2003. We obtained ICD-9 information on 281,763 pediatric ED visits from 27 hospitals in the St. Louis, MO metropolitan area. The relationship between EC and pediatric asthma ED visits, controlling for season, weekend exposure, allergens, and other pollutants known to exacerbate asthma, was assessed using Poisson generalized estimating equations using a 1-day lag between exposure and ED visit. We evaluated the interaction of EC and temperature and EC and weekend vs. weekday exposure. An interaction effect existed between EC and temperature for 11-17-year-olds during the summer and winter seasons. During the summer, a 0.10 microg/m(3) increase in EC resulted in a 9.45% increase in asthma ED visits among 11-17-year-olds (95%CI = 1.02,1.17) at the median seasonal temperature (86.5 degrees F). This risk increased with increasing temperature. During the winter, a 0.10 microg/m(3) increase in EC resulted in 2.80% increase in asthma ED visits among 11-17-year-olds (95%CI = 1.01,1.05) at the median seasonal temperature (43.3 degrees F). This risk increased with decreasing temperature. Among 11-17-year-olds, daily number of asthma ED visits is associated with increased levels of EC at higher temperatures in the summer and lower temperatures in the winter.

Objective: This experiment was designed to test if controlled exposure to particles and ozone would result in decreased heart rate variability (HRV)., Methods: Five asthmatic adults were exposed for 4 hours to; filtered-air, carbon and ammonium nitrate particles, and particles and ozone. Twenty-minute electrocardiograms were obtained before and after each exposure., Results: Standard deviation of all normal-to-normal beat intervals (SDNN) decreased significantly across particles and ozone exposure compared with across filtered-air exposure (P = 0.01). Changes in SDNN-I (P = 0.04) and normalized low and high frequency (P = 0.02) were also seen across particles and ozone exposure; although these changes may best be characterized as trends given the small sample size. No significant changes in HRV were seen across the filtered-air or particles-only exposures., Conclusions: The results of this study suggest that combined particle and ozone exposure may decrease HRV in asthmatics. Further investigation is needed to confirm this finding.

Rationale: Recent epidemiologic studies have shown that homocysteine, a sulfur-containing amino acid formed during the metabolism of methionine, is a risk factor for atherosclerosis, myocardial infarction, stroke, and thrombosis. Particulate air pollution has been related to cardiovascular death and hospital admission, but the underlying mechanisms are not fully elucidated., Objectives: We examined the associations between ambient particulate air pollution and plasma concentrations of homocysteine among 960 community-residing older men (mean age, 73.6 +/- 6.9 yr)., Methods: Total homocysteine in plasma, measured using high-performance liquid chromatography with fluorescence detection, was regressed on each ambient particulate pollutant (black carbon, organic carbon, sulfate or PM(2.5)), and effect modification by plasma and dietary B vitamins (folate, B6, and B12) was examined., Measurements and Main Results: The median concentration of total homocysteine was 10.6 micromol/L. Statistically significant positive associations of total homocysteine were observed with traffic-related particles (black carbon and organic carbon). No association was observed with sulfate, an indicator of coal combustion particles, or PM(2.5) (particulate matter < or = 2.5 microm in aerodynamic diameter). The effects of black carbon and organic carbon were more pronounced in persons with low concentrations of plasma folate and vitamin B12., Conclusions: Exposures to ambient particles, particularly from traffic, are associated with elevated plasma total homocysteine. Homocysteine may be a component or biological marker of the oxidation pathways underlying the effect of ambient particles on the cardiovascular system.

A 68-year-old woman with insulin-dependent diabetes mellitus presented with blue nodules on the ventral aspect of the thorax. According to the past history, these lesions had developed repeatedly. She had already had bilateral mastectomies and lymph node dissection. The histologic diagnosis was always mastitis with plasma cells and no neoplasia. Yet another biopsy was taken; the subcutis was stained blue-black. Histology revealed exogenous black pigment and mastitis. With Raman spectroscopy the pigment was identified as carbon black, which is a component of India ink. These findings together with the unusual course of the disease suggested the diagnosis of an artificial disorder. The likely conclusion is that our patient, over years, used her own (insulin) syringe to inject India ink into her skin and subcutaneous tissue; the damaging effect and tissue reaction was probably caused by preservatives such as phenol.

F-18 FDG PET-CT is a useful modality for monitoring residual or recurrent tumors after surgical resection. We report on 3 patients with intraperitoneal charcoal-induced granulomas mimicking peritoneal carcinomatosis on PET-CT images. Two of them underwent a radical gastrectomy because of advanced gastric cancer, and the other underwent a hemicolectomy because of sigmoid colon cancer. All 3 patients had a history of intraperitoneal chemotherapy using mitomycin C bound to activated carbon particles during surgery. Follow-up PET-CT studies demonstrated increased FDG uptake mimicking peritoneal carcinomatosis on PET images alone. However, the accompanying noncontrast CT showed variously shaped hyperdense nodules in the dependent positions of the peritoneal cavity, including the paracolic gutter and rectovesical space, indicating charcoal-induced granulomas rather than peritoneal carcinomatosis.

A primary means to reduce environmental levels of diesel particulate matter (DPM) exposure to miners is to reduce the amount of DPM emission from the engine. A quick and economic method to estimate engine particulate emission levels has been developed. The method relies on the measurement of pressure increase across a filter element that is briefly used to collect a DPM sample directly from the engine exhaust. The method has been refined with the inclusion of an annular aqueous denuder to the tube which permits dry filter samples to be obtained without addition of dilution air. Tailpipe filter samples may then be directly collected in hot and water-supersaturated exhaust gas flows from water bath-cooled coal mine engines without the need for dilution air. Measurement of a differential pressure (DP) increase with time has been related to the mass of elemental carbon (EC) on the filter. Results for laboratory and field measurements of the method showed agreement between DP increase and EC collected on the filter with R(2) values >0.86. The relative standard deviation from replicate samples of DP and EC was 0.16 and 0.11, respectively. The method may also have applications beyond mining, where qualitative evaluation of engine emissions is desirable to determine if engine or control technology maintenance may be required.

We have utilized a range of manufactured or commercial nanoparticulate materials, including surrogate carbon nano-PM along with combustion-generated carbonaceous (soot) nano-PM characteristic of environmental nano- PM (both indoor and outdoor) to investigate and compare their cytotoxic response in vitro with an immortalized human epithelial (lung model) cell line (A549). These have included nano-Ag, Al2O3, TiO2, Fe2O3, ZrO2, Si3N4, chrysotile asbestos, BC, 2 types of MWCNT-aggregate PM (MWCNT-R and MWCNT-N), and high-volume glass fiber collected soots: candle, wood, diesel (truck), tire, and 3-types of natural gas kitchen burner-generated soots: yellow (fuel-rich) flame, low-flow blue flame, and normal flow blue flame soot PM. These carbonaceous nano-PM species can be found in either the indoor and outdoor environments or microenvironments. Two-day and two-week in-vitro cultures of A549 showed cell death (or decreased cell viability) for all nanoparticulate materials, but especially significant for all but the TiO2 and candle, wood, and diesel PM. The natural gas kitchen burner combustion PM cell death response was characteristic of BC and MWCNT PM. There was no correlation with total PAH content of the soot PM. Cytokine release (IL-6, IL-8) was detected for the Ag, Fe2 O3, asbestos, BC and the MWCNT PM. Reactive oxygen species (ROS) production was also detected for Ag, Fe2 O3, ZrO2, asbestos, BC, and the MWCNT aggregate PM, as well as the natural gas kitchen burner combustion PM. TEM, FESEM, and optical microscopy examination of these nanomaterials illustrate the wide range in PM morphologies and crystallinities as well as cell morphologies. Taken together, these results illustrate proinflammatory and related respiratory health issues in relation to environmental nanoparticulates.

While studies show that ultrafine and fine particles can be translocated from the lungs to the central nervous system, the possible neurodegenerative effect of air pollution remains largely unexplored. The authors examined the relation between black carbon, a marker for traffic particles, and cognition among 202 Boston, Massachusetts, children (mean age = 9.7 years (standard deviation, 1.7)) in a prospective birth cohort study (1986-2001). Local black carbon levels were estimated using a validated spatiotemporal land-use regression model (mean predicted annual black carbon level, 0.56 mug/m(3) (standard deviation, 0.13)). The Wide Range Assessment of Memory and Learning and the Kaufman Brief Intelligence Test were administered for assessment of cognitive constructs. In analysis adjusting for sociodemographic factors, birth weight, blood lead level, and tobacco smoke exposure, black carbon (per interquartile-range increase) was associated with decreases in the vocabulary (-2.2, 95% confidence interval (CI): -5.5, 1.1), matrices (-4.0, 95% CI: -7.6, -0.5), and composite intelligence quotient (-3.4, 95% CI: -6.6, -0.3) scores of the Kaufman Brief Intelligence Test and with decreases on the visual subscale (-5.4, 95% CI: -8.9, -1.9) and general index (-3.9, 95% CI: -7.5, -0.3) of the Wide Range Assessment of Memory and Learning. Higher levels of black carbon predicted decreased cognitive function across assessments of verbal and nonverbal intelligence and memory constructs.

Nickel-titanium (NiTi) has been used for implants in orthodontics due to the unique properties such as shape memory effect and superelasticity. However, NiTi alloys are eroded in the oral cavity because they are immersed by saliva with enzymolysis. Their reactions lead corrosion and nickel release into the body. The higher concentrations of Ni release may generate harmful reactions. Ni release causes allergenic, toxic and carcinogenic reactions. It is well known that diamond-like carbon (DLC) films have excellent properties, such as extreme hardness, low friction coefficients, high wear resistance. In addition, DLC film has many other superior properties as a protective coating for biomedical applications such as biocompatibility and chemical inertness. Therefore, DLC film has received enormous attention as a biocompatible coating. In this study, DLC film coated NiTi orthodontic archwires to protect Ni release into the oral cavity. Each wire was immersed in physiological saline at the temperature 37 degrees C for 6 months. The release concentration of Ni ions was detected using microwave induced plasma mass spectrometry (MIP-MS) with the resolution of ppb level. The toxic effect of Ni release was studied the cell growth using squamous carcinoma cells. These cells were seeded in 24 well culture plates and materials were immersed in each well directly. The concentration of Ni ions in the solutions had been reduced one-sixth by DLC films when compared with non-coated wire. This study indicated that DLC films have the protective effect of the diffusion and the non-cytotoxicity in corrosive environment.

1. The general term 'nanoparticle' (NP) is used to define any particle less than 100 nm in at least one dimension and NPs are generally classified as natural, anthropogenic or engineered in origin. Anthropogenic, also referred to as 'ultrafine' particles (UFPs), are predominately combustion derived and are characterized by having an equivalent spherical diameter less than 100 nm. 2. These particles, considered to be 'combustion-derived nanoparticles' (CDNPs), are of toxicological interest given their nanosized dimensions, with properties not displayed by their macroscopic counterparts. 3. The pulmonary deposition efficiency of inhaled UFPs, along with their large surface areas and bound transition metals, is considered important in driving the emerging health effects linked to respiratory toxicity. 4. The toxicology of CDNPs is currently used to predict the health outcomes in humans following exposure to manufactured NPs. Their similar physicochemistry would suggest similar adverse health effects (i.e. pulmonary (and perhaps cardiac) toxicity). As such, it is essential to fully understand CDNP nanotoxicology in order to minimize occupational and environmental exposure.

Purpose: The high relative biologic effectiveness (RBE) of high-linear energy transfer (LET) heavy-ion radiation has enabled powerful radiotherapy. The potential risk of later onset of secondary cancers, however, has not been adequately studied. We undertook the present study to clarify the RBE of therapeutic carbon ion radiation and molecular changes that occur in the rat mammary cancer model., Methods and Materials: We observed 7-8-week-old rats (ACI, F344, Wistar, and Sprague-Dawley) until 1 year of age after irradiation (0.05-2 Gy) with either 290 MeV/u carbon ions with a spread out Bragg peak (LET 40-90 keV/mum) generated from the Heavy-Ion Medical Accelerator in Chiba or (137)Cs gamma-rays., Results: Carbon ions significantly induced mammary carcinomas in Sprague-Dawley rats but less so in other strains. The dose-effect relationship for carcinoma incidence in the Sprague-Dawley rats was concave downward, providing an RBE of 2 at a typical therapeutic dose per fraction. In contrast, approximately 10 should be considered for radiation protection at low doses. Immunohistochemically, 14 of 18 carcinomas were positive for estrogen receptor alpha. All carcinomas examined were free of common H-ras and Tp53 mutations. Importantly, lung metastasis (7%) was characteristic of carbon ion-irradiated rats., Conclusions: We found clear genetic variability in the susceptibility to carbon ion-induced mammary carcinomas. The high RBE for carbon ion radiation further supports the importance of precise dose localization in radiotherapy. Common point mutations in H-ras and Tp53 were not involved in carbon ion induction of rat mammary carcinomas.

Objective: It is still unknown whether specific components in fine particles are associated with heart rate variability (HRV) reduction., Methods: We recruited 46 patients with or at risk for cardiovascular diseases to measure 24-hour HRV by ambulatory electrocardiographic monitoring. Fixed-site air-monitoring stations were used to represent participants' exposures to particles with aerodynamic diameters less than 10 microm (PM 10) and 2.5 microm (PM2.5), and particulate components of sulfate, nitrate, organic carbon (OC) and elemental carbon, and gaseous pollutants., Results: We found that HRV reduction was associated with sulfate, OC, and PM2.5 but not with the other five pollutants in single-pollutant models. Sulfate was found to remain in significant association with HRV reduction adjusting for OC and PM2.5 in three-pollutant models., Conclusions: Exposures to sulfate and OC in PM2.5 were associated with HRV reduction in patients with or at risk for cardiovascular diseases.

The development of a clinically durable small-diameter vascular graft as well as permanently implantable biosensors and artificial organ systems that interface with blood, including the artificial heart, kidney, liver, and lung, remain limited by surface-induced thrombotic responses. Recent breakthroughs in materials science, along with a growing understanding of the molecular events that underlay thrombosis, has led to the design and clinical evaluation of a variety of biologically active coatings that inhibit components of the coagulation pathway and platelet responses by surface immobilization or controlled release of bioactive agents. This report reviews recent progress in generating synthetic thromboresistant surfaces that inhibit (1) protein and cell adsorption, (2) thrombin and fibrin formation, and (3) platelet activation and aggregation.