Detecting and characterizing special nuclear material for nuclear nonproliferation applications.

There is an urgent need for new, better instrumentation and techniques for detecting and characterizing special nuclear material (SNM), i.e., highly enriched uranium and plutonium. The development of improved instruments and techniques requires experiments performed with the SNM itself, which is of limited availability. This paper describes the findings of experiments performed at the National Criticality Experiments Research Center conducted using new instruments and techniques on unclassified, kg-quantity SNM objects. These experiments, performed in the framework of the Department of Energy, National Nuclear Security Administration Consortium for Monitoring, Technology, and Verification, focused on detecting, characterizing, and localizing SNM samples with masses ranging from 3.3 to 13.8 kg, including plutonium and highly enriched uranium using prototype detectors and techniques. The work demonstrates SNM detection and characterization using recently-developed prototype detection systems. Specifically, we present new results in passive detection and imaging of plutonium and uranium objects using gamma-ray and dual particle (fast neutron and gamma-ray) imaging. We also present a new analysis of the delayed neutron emissions during active interrogation of uranium using a neutron generator.

DUAL-PARTICLE DOSEMETER BASED ON ORGANIC SCINTILLATOR.

Traditionally available handheld dosemeters are generally sensitive to only one type of radiation: neutrons or photons. Some dosemeters also rely on very specific attenuation correlations between response and dose, are not scalable in size and multiple dosemeters are required to characterise mixed-particle fields. The research presented here serves as a proof-of-concept for a method to simultaneously measure dose rates from neutrons and photons using a particle discriminating organic scintillation detector without the need for spectral deconvolution. The method was compared with traditional instruments and to simulation. Isotopic photon dose rates measured with this method were within 4% of simulated truth, whereas fission spectrum neutron dose rates were measured within 21%. Measurements of dose rates from both particles agree with simulated truth better than traditional instruments. This new method allows for measurement of dose equivalent from both neutrons and photons with a single instrument and no reliance on spectral deconvolution.

Angular distribution of neutron production by proton and carbon-ion therapeutic beams.

Carbon-ion beams are increasingly used in the clinical practice for external radiotherapy treatments of deep-seated tumors. At therapeutic energies, carbon ions yield significant secondary products, including neutrons, which may be of concern for the radiation protection of the patient and personnel. We simulated the neutron yield produced by proton and carbon-ion pencil beams impinging on a clinical phantom at three different angles: 15°, 45° and 90°, with respect to the beam axis. We validated the simulated results using the measured response of organic scintillation detectors. We compared the results obtained with FLUKA 2011.2 and MCNPX 2.7.0 based on three different physics models: Bertini, Isabel, and CEM. Over the different ions, energies, and angles, the FLUKA simulation results agree better with the measured data, compared to the MCNPX results. Simulations of carbon ions at low angles exhibit both the highest deviation from measured data and inter-model discrepancy, which is probably due to the different treatment of the pre-equilibrium stage. The reported neutron yield results could help in the comparison of carbon-ion and proton treatments in terms of secondary neutron production for radiation protection applications.

Electromagnetic Interference in Measurements of Radial Stress During Split Hopkinson Pressure Bar Experiments.

Split Hopkinson pressure bar experiments on soils are often carried out using a rigid steel confining ring to provide plane strain conditions, and measurements of the circumferential strain in the ring can be used to infer the radial stress on the surface of the specimen. Previous experiments have shown evidence of irregular electromagnetic interference in measurements of radial stress, which obscures the signals and impedes analysis. The development of robust constitutive models for soils in blast and impact events relies on the accurate characterisation of this behaviour, and so it is necessary to isolate and remove the source of interference. This paper uses an induction coil to identify the source of the anomalous signals, which are found to be due to induced currents in the gauge lead wires from the movement of magnetised pressure bars (martensitic stainless steel, 440C). Comparative experiments on sand and rubber specimens are used to show that the deforming soil specimen does not make a significant contribution to this activity, and recommendations are made on reducing electromagnetic interference to provide reliable radial stress measurements.

A scintillator-based approach to monitor secondary neutron production during proton therapy.

PURPOSE: The primary objective of this work is to measure the secondary neutron field produced by an uncollimated proton pencil beam impinging on different tissue-equivalent phantom materials using organic scintillation detectors. Additionally, the Monte Carlo code mcnpx-PoliMi was used to simulate the detector response for comparison to the measured data. Comparison of the measured and simulated data will validate this approach for monitoring secondary neutron dose during proton therapy. METHODS: Proton beams of 155- and 200-MeV were used to irradiate a variety of phantom materials and secondary particles were detected using organic liquid scintillators. These detectors are sensitive to fast neutrons and gamma rays: pulse shape discrimination was used to classify each detected pulse as either a neutron or a gamma ray. The mcnpx-PoliMi code was used to simulate the secondary neutron field produced during proton irradiation of the same tissue-equivalent phantom materials. RESULTS: An experiment was performed at the Loma Linda University Medical Center proton therapy research beam line and corresponding models were created using the mcnpx-PoliMi code. The authors' analysis showed agreement between the simulations and the measurements. The simulated detector response can be used to validate the simulations of neutron and gamma doses on a particular beam line with or without a phantom. CONCLUSIONS: The authors have demonstrated a method of monitoring the neutron component of the secondary radiation field produced by therapeutic protons. The method relies on direct detection of secondary neutrons and gamma rays using organic scintillation detectors. These detectors are sensitive over the full range of biologically relevant neutron energies above 0.5 MeV and allow effective discrimination between neutron and photon dose. Because the detector system is portable, the described system could be used in the future to evaluate secondary neutron and gamma doses on various clinical beam lines for commissioning and prospective data collection in pediatric patients treated with proton therapy.

Designing simulator tools for rail research: the case study of a train driving microworld.

The microworld simulator paradigm is well established in the areas of ship-navigation and spaceflight, but has yet to be applied to rail. This paper presents a case study aiming to address this research gap, and describes the development of a train driving microworld as a tool to overcome some common research barriers. A theoretical framework for microworld design is tested and used to explore some key methodological issues and characteristics of train driving, enhancing theory development and providing a useful guideline for the designers of other collision-avoidance systems. A detailed description is given of the ATREIDES (Adaptive Train Research Enhanced Information Display & Environment Simulator) microworld, which simulates the work environment of a train driver in a high-speed passenger train. General indications of the testable driving scenarios that may be simulated are given, and an example of an ATREIDES-based study is presented to illustrate its applied research potential. The article concludes with a review of the design process, considers some strengths and limitations, and explores some future initiatives towards enhancing the systematic study of rail research in the human factors community.

Metabolism and functions of highly unsaturated fatty acids: an update.

This review briefly examines the recent progress in knowledge about the synthesis and degradation of highly unsaturated fatty acids (HUFA) and their functions. Following the cloning of mammalian Delta6-desaturase (D6D), the D6D mRNA was found in many tissues, including adult brain, maternal organs, and fetal tissue, suggesting an active synthesis of HUFA in these tissues. The cloning also confirmed the long-postulated hypothesis that the same pathway is followed in n-6 and n-3 HUFA synthesis. Dietary n-6 and n-3 HUFA both induce fatty acid oxidation enzymes in peroxisomes when compared to their respective precursor polyunsaturated fatty acids. This suggests that peroxisomes may be the primary site of HUFA degradation when HUFA are supplied in excess from the diet. Peroxisome proliferators strongly induce the enzymes for the HUFA synthesis. The mechanism of this induction is currently unknown. Recent studies revealed new HUFA functions that are not mediated by eicosanoids. These functions include endocytosis/exocytosis, ion-channel modulation, DNA polymerase inhibition, and regulation of gene expression. These new discoveries will enable us to re-examine the underlying mechanisms for the classical symptoms of essential fatty acid deficiency as well as vitamin E deficiency. Progress has also been made in understanding the mechanism by which dietary HUFA reduce body fat deposition. One mechanism is induction of genes for fatty acid oxidation, which is mediated by peroxisome proliferator-activated receptor-alpha. Another likely mechanism is that HUFA suppress genes for fatty acid synthesis by reducing both mRNA and protein maturation of sterol regulatory element binding protein-1.

Transcriptional regulation of fatty acid synthase gene by somatotropin in 3T3-F442A adipocytes.

Somatotropin (ST) antagonizes insulin stimulation of fatty acid synthase (FAS) enzyme activity and gene transcription in adipocytes. Previous studies have shown that an insulin response element (IRE) is located in the proximal region of the FAS promoter (-71 to -50) and upstream stimulatory factor (USF) 1 binds to this IRE. The present study was conducted to initially evaluate whether there is a somatotropin response element (STRE) in the 5'flanking region of the FAS gene and to determine whether USF1 mediates the effect of ST on FAS gene transcription in 3T3-F442A adipocytes. Two 5' deletion FAS promoter constructs (pFAS-CATS4 and pFAS-CAT5), which contain the 5' flanking sequences of the rat FAS gene at -112 to +65 and -2195 to +65, respectively, were stably transfected into 3T3-F442A preadipocytes. Insulin stimulated chloramphenicol acetyltransferase (CAT) activity 1.7- and 4.7-fold (P < 0.05) in 3T3-F442A adipocytes transfected with pFAS-CATS4 and pFAS-CAT5, respectively. In contrast, bovine somatotropin (bST) attenuated the stimulatory effect of insulin on CAT activity by approximately 60% (P < 0.05) in both constructs. When 3T3-F442A adipocytes were treated with insulin (10 ng/mL) or insulin (10 ng/mL) plus bST (100 ng/mL) for 24, 48, or 72 h, neither insulin nor bST significantly affected USF1 mRNA levels. When human USF1 (hUSF1) cDNA probe was used, however, insulin increased the abundance of an unidentified transcript (named hUSF1-like mRNA) 11- to 25-fold (P < 0.05) and ST decreased the stimulatory effect of insulin on hUSF1-like mRNA levels by 50 to 90% (P < 0.05). Western blot analyses of nuclear extracts from cells treated with insulin (10 ng/mL) or insulin (10 ng/mL) plus bST (100 ng/mL) for 48 h demonstrated that the abundance of USF1 was not affected by insulin or ST. Furthermore, electrophoretic mobility shift analyses (EMSA) of nuclear extracts revealed that neither insulin nor ST had an effect on the binding of USF1 to the IRE. These results suggest that a STRE may be located within the first 112 bp of the FAS promoter and that USF1 does not directly mediate the effect of ST on transcription of the FAS gene in 3T3-F442A adipocytes.

Nonalcoholic steatosis and steatohepatitis. I. Molecular mechanism for polyunsaturated fatty acid regulation of gene transcription.

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the n-3 family, play pivotal roles as "fuel partitioners" in that they direct fatty acids away from triglyceride storage and toward oxidation and they enhance glucose flux to glycogen. In doing this, PUFA may reduce the risk of enhanced cellular apoptosis associated with excessive cellular lipid accumulation. PUFA exert their beneficial effects by upregulating the expression of genes encoding proteins involved in fatty acid oxidation while simultaneously downregulating genes encoding proteins of lipid synthesis. PUFA govern oxidative gene expression by activating the transcription factor peroxisome proliferator-activated receptor-alpha. PUFA suppress lipogenic gene expression by reducing the nuclear abundance and DNA binding affinity of transcription factors responsible for imparting insulin and carbohydrate control to lipogenic and glycolytic genes. In particular, PUFA suppress the nuclear abundance and expression of sterol regulatory element binding protein-1 and reduce the DNA binding activities of nuclear factor Y, stimulatory protein 1, and possibly hepatic nuclear factor-4. Collectively, the studies discussed suggest that the fuel "repartitioning" and gene expression actions of PUFA should be considered among the criteria used in defining the dietary needs of n-6 and n-3 fatty acids and in establishing the dietary ratio of n-6 to n-3 fatty acids needed for optimum health benefit.

Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome.

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the (n-3) family, play pivotal roles as "fuel partitioners" in that they direct fatty acids away from triglyceride storage and toward oxidation, and that they enhance glucose flux to glycogen. In doing this, PUFA may protect against the adverse symptoms of the metabolic syndrome and reduce the risk of heart disease. PUFA exert their beneficial effects by up-regulating the expression of genes encoding proteins involved in fatty acid oxidation while simultaneously down-regulating genes encoding proteins of lipid synthesis. PUFA govern oxidative gene expression by activating the transcription factor peroxisome proliferator-activated receptor alpha. PUFA suppress lipogenic gene expression by reducing the nuclear abundance and DNA-binding affinity of transcription factors responsible for imparting insulin and carbohydrate control to lipogenic and glycolytic genes. In particular, PUFA suppress the nuclear abundance and expression of sterol regulatory element binding protein-1 and reduce the DNA-binding activities of nuclear factor Y, Sp1 and possibly hepatic nuclear factor-4. Collectively, the studies discussed suggest that the fuel "repartitioning" and gene expression actions of PUFA should be considered among criteria used in defining the dietary needs of (n-6) and (n-3) and in establishing the dietary ratio of (n-6) to (n-3) needed for optimum health benefit.

Involvement of a unique carbohydrate-responsive factor in the glucose regulation of rat liver fatty-acid synthase gene transcription.

Refeeding carbohydrate to fasted rats induces the transcription of genes encoding enzymes of fatty acid biosynthesis, e.g. fatty-acid synthase (FAS). Part of this transcriptional induction is mediated by insulin. An insulin response element has been described for the fatty-acid synthase gene region of -600 to +65, but the 2-3-fold increase in fatty-acid synthase promoter activity attributable to this region is small compared with the 20-30-fold induction in fatty-acid synthase gene transcription observed in fasted rats refed carbohydrate. We have previously reported that the fatty-acid synthase gene region between -7382 and -6970 was essential for achieving high in vivo rates of gene transcription. The studies of the current report demonstrate that the region of -7382 to -6970 of the fatty-acid synthase gene contains a carbohydrate response element (CHO-RE(FAS)) with a palindrome sequence (CATGTGn(5)GGCGTG) that is nearly identical to the CHO-RE of the l-type pyruvate kinase and S(14) genes. The glucose responsiveness imparted by CHO-RE(FAS) was independent of insulin. Moreover, CHO-RE(FAS) conferred glucose responsiveness to a heterologous promoter (i.e. l-type pyruvate kinase). Electrophoretic mobility shift assays demonstrated that CHO-RE(FAS) readily bound a unique hepatic ChoRF and that CHO-RE(FAS) competed with the CHO-RE of the l-type pyruvate kinase and S(14) genes for ChoRF binding. In vivo footprinting revealed that fasting reduced and refeeding increased ChoRF binding to CHO-RE(FAS). Thus, carbohydrate responsiveness of rat liver fatty-acid synthase appears to require both insulin and glucose signaling pathways. More importantly, a unique hepatic ChoRF has now been shown to recognize glucose responsive sequences that are common to three different genes: fatty-acid synthase, l-type pyruvate kinase, and S(14).

Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay.

The reduction in hepatic abundance of sterol regulatory element binding protein-1 (SREBP-1) mRNA and protein associated with the ingestion of polyunsaturated fatty acids (PUFA) appears to be largely responsible for the PUFA-dependent inhibition of lipogenic gene transcription. Our initial studies indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA. Nuclear run-on assays suggested PUFA reduced SREBP-1 mRNA by post-transcriptional mechanisms. In this report we demonstrate that PUFA enhance the decay of both SREBP-1a and -1c. When rat hepatocytes in monolayer culture were treated with albumin-bound 20:4(n-6) or 20:5(n-3) the half-life of total SREBP-1 mRNA was reduced by 50%. Ribonuclease protection assays revealed that the decay of SREBP-1c mRNA was more sensitive to PUFA than was SREBP-1a, i.e. the half-life of SREBP-1c and -1a was reduced from 10.0 to 4.6 h and 11.6 to 7.6 h, respectively. Interestingly, treating the hepatocytes with the translational inhibitor, cycloheximide, prevented the PUFA-dependent decay of SREBP-1. This suggests that SREBP-1 mRNA may need to undergo translation to enter the decay process, or that the decay process requires the synthesis of a rapidly turning over protein. Although the mechanism by which PUFA accelerate SREBP-1 mRNA decay remains to be determined, cloning and sequencing of the 3'-untranslated region for the rat SREBP-1 transcript revealed the presence of an A-U-rich region that is characteristic of a destablizing element.

Copper deficiency induces hepatic fatty acid synthase gene transcription in rats by increasing the nuclear content of mature sterol regulatory element binding protein 1.

Dietary copper (Cu) deficiency results in an accelerated rate of hepatic fatty acid synthase gene transcription and an enhanced rate of hepatic lipid synthesis. Because the nuclear transcription factor sterol regulatory element binding protein-1 (SREBP-1) is a strong enhancer of fatty acid synthase promoter activity, it was hypothesized that Cu deficiency induces fatty acid synthase gene transcription by increasing the nuclear localization of mature SREBP-1. Male weanling rats were pair-fed a Cu-adequate (6.0 mg/kg) or Cu-deficient (0.6 mg/kg) diet (AIN-93) for 28 d. DNase I hypersensitivity site mapping of the hepatic fatty acid synthase gene revealed the presence of four major hypersensitivity sites located at -8700 to -8600, -7300 to -6900, -600 to -400 and -100 to +50. Although Cu deficiency did not change the hypersensitivity site pattern or intensity, in vitro footprinting of the region between -100 and +50 indicated that Cu deficiency enhanced DNA protein interactions within this region. The sequence between -68 and -58 contains the DNA recognition sequence for SREBP-1 and upstream stimulatory element-1 (USF-1). Western blot analysis revealed that the dietary Cu deficiency increased the hepatic nuclear content of mature SREBP-1 by 150% (P: < 0.05), and it concomitantly decreased the membrane content of precursor SREBP-1 by 45% (P: < 0.05). Changes in the hepatic distribution of SREBP-1 associated with Cu deficiency were not accompanied by changes in SREBP-1 mRNA. The nuclear content of USF-1 was unaffected by dietary Cu status. The hepatic increase in mature SREBP-1 of Cu-deficient rats was accompanied by a 400% increase and an 80% decrease in the abundance of fatty acid synthase and cholesterol 7-alpha hydroxylase mRNA, respectively. hepatic These data indicate that a Cu deficiency stimulates hepatic lipogenic gene expression by increasing the hepatic translocation of mature SREBP-1.

Polyunsaturated fatty acid regulation of gene transcription: a mechanism to improve energy balance and insulin resistance.

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the n-3 family, play essential roles in the maintenance of energy balance and glucose metabolism. The data discussed indicate that dietary PUFA function as fuel partitioners in that they direct glucose toward glycogen storage, and direct fatty acids away from triglyceride synthesis and assimilation and toward fatty acid oxidation. In addition, the n-3 family of PUFA appear to have the unique ability to enhance thermogenesis and thereby reduce the efficiency of body fat deposition. PUFA exert their effects on lipid metabolism and thermogenesis by upregulating the transcription of the mitochondrial uncoupling protein-3, and inducing genes encoding proteins involved in fatty acid oxidation (e.g. carnitine palmitoyltransferase and acyl-CoA oxidase) while simultaneously down-regulating the transcription of genes encoding proteins involved in lipid synthesis (e.g. fatty acid synthase). The potential transcriptional mechanism and the transcription factors affected by PUFA are discussed. Moreover, the data are interpreted in the context of the role that PUFA may play as dietary factors in the development of obesity and insulin resistance. Collectively the results of these studies suggest that the metabolic functions governed by PUFA should be considered as part of the criteria utilized in defining the dietary needs for n-6 and n-3 PUFA, and in establishing the optimum dietary ratio for n-6:n-3 fatty acids.

Regulation of hepatic delta-6 desaturase expression and its role in the polyunsaturated fatty acid inhibition of fatty acid synthase gene expression in mice.

Dietary polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families uniquely suppress the expression of lipogenic genes while concomitantly inducing the expression of genes encoding proteins of fatty acid oxidation. Although considerable progress has been made toward understanding the nuclear events affected by PUFA, the intracellular mediator responsible for the regulation of hepatic lipogenic gene expression remains unclear. On the basis of earlier fatty acid composition studies, we hypothesized that the Delta-6 desaturase pathway was essential for the production of the fatty acid regulator of gene expression. To address this hypothesis, male BALB/c mice (n = 8/group) were fed for 5 d a high glucose, fat-free diet (FF) or the FF plus 50 g/kg 18:2(n-6) with and without eicosa-5, 8,11,14-tetraynoic acid (ETYA) (200 mg/kg diet), a putative inhibitor of the Delta-6 desaturase pathway. ETYA had no effect on food intake or weight gain, but it completely prevented 18:2(n-6) from suppressing the hepatic abundance of fatty acid synthase mRNA. ETYA ingestion was associated with a decrease in the hepatic content of 20:4(n-6) and an increase in the amount of 18:2(n-6). The fatty acid composition changes elicited by ETYA were accompanied by a decrease in the enzymatic activity of Delta-6 desaturase. Interestingly, the hepatic abundance of Delta-6 desaturase mRNA was actually induced by ETYA one- to twofold. When the product of Delta-6 desaturase, i.e., 18:3(n-6), was added to the ETYA plus 18:2(n-6) diet, the hepatic content of 20:4(n-6) was normalized. In addition, 18:3(n-6) consumption reduced the level of hepatic Delta-6 desaturase mRNA by 50% and completely prevented the increase in fatty acid synthase mRNA that was associated with ETYA ingestion. Apparently, Delta-6 desaturation is an essential step for the PUFA regulation of the fatty acid synthase gene transcription. Finally, the suppression of Delta-6 desaturase by PUFA and its induction by ETYA suggest that the Delta-6 desaturase gene may be regulated by two different lipid-dependent mechanisms.

Omega-3 polyunsaturated fatty acid regulation of gene expression.

This review describes the mechanisms by which polyunsaturated fatty acids regulate the activity of the nuclear transcription factors, peroxisome proliferator-activated receptor and sterol regulatory element binding protein-1, and it describes the role that the peroxisome proliferator-activated receptor and sterol regulatory element binding protein-1 play in coordinating the regulation of lipid synthesis, lipid oxidation, and thermogenesis. Finally, the requirement for dietary polyunsaturated fatty acids, particularly n-3 fatty acids, is defined in terms of the effects polyunsaturated fatty acids exert on gene expression and the role that these effects play in overall energy balance.

Cloning, expression, and fatty acid regulation of the human delta-5 desaturase.

Arachidonic (20:4(n-6)), eicosapentaenoic (20:5(n-3)), and docosahexaenoic (22:6(n-3)) acids are major components of brain and retina phospholipids, substrates for eicosanoid production, and regulators of nuclear transcription factors. One of the two rate-limiting steps in the production of these polyenoic fatty acids is the desaturation of 20:3(n-6) and 20:4(n-3) by Delta-5 desaturase. This report describes the cloning and expression of the human Delta-5 desaturase, and it compares the structural characteristics and nutritional regulation of the Delta-5 and Delta-6 desaturases. The open reading frame of the human Delta-5 desaturase encodes a 444-amino acid peptide which is identical in size to the Delta-6 desaturase and which shares 61% identity with the human Delta-6 desaturase. The Delta-5 desaturase contains two membrane-spanning domains, three histidine-rich regions, and a cytochrome b(5) domain that all align perfectly with the same domains located in the Delta-6 desaturase. Expression of the open reading frame in Chinese hamster ovary cells instilled the ability to convert 20:3(n-6) to 20:4(n-6). Northern analysis revealed that many human tissues including skeletal muscle, lung, placenta, kidney, and pancreas expressed Delta-5 desaturase mRNA, but Delta-5 desaturase was most abundant in the liver, brain, and heart. However, in all tissues, the abundance of Delta-5 desaturase mRNA was much lower than that observed for the Delta-6 desaturase. When rats were fed a diet containing 10% safflower oil or menhaden fish oil, the level of hepatic mRNA for Delta-5 and Delta-6 desaturase was only 25% of that found in the liver of rats fed a fat-free diet or a diet containing triolein. Finally, a BLAST and Genemap search of the human genome revealed that the Delta-5 and Delta-6 desaturase genes reside in reverse orientation on chromosome 11 and that they are separated by <11,000 base pairs.

Spontaneous abortion in the British semiconductor industry: An HSE investigation. Health and Safety Executive.

BACKGROUND: The UK Health and Safety Executive (HSE) conducted a study to examine the risk of spontaneous abortion (SAB) in British female semiconductor industry workers, following reports from the USA which suggested an association between risk of SAB and work in fabrication rooms and/or exposure to ethylene glycol ethers. METHODS: A nested case-control study based on 2,207 women who had worked at eight manufacturing sites during a 5-year retrospective time frame was established; 36 cases were matched with 80 controls. RESULTS: The overall SAB rate in the industry was 10.0%. (65 SABs/651 pregnancies) The crude odds ratio (OR) for fabrication work was 0.65 (95% CI 0.30-1.40). This was essentially unchanged after adjustment for a range of potential confounding factors in the first 3 months of pregnancy and was reduced to 0.58 (95% CI 0.26-1.30) after adjustment for smoking in the previous 12 months. There were no statistically significantly elevated ORs for any work group or any specific chemical or physical exposure in the industry. CONCLUSIONS: There is no evidence of an increased risk of SAB in the British semiconductor industry. Am. J. Ind. Med. 36:557-572, 1999. Published 1999 Wiley-Liss, Inc.