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Adolescents with Hodgkin lymphoma have worse disease outcomes than children. Whether these differences persist within clinical trials is unknown. We examined survival, by age, in patients receiving response-adapted therapy for Hodgkin lymphoma on Children's Oncology Group (COG) trials.Patients (aged 1-21 years) diagnosed with classical Hodgkin lymphoma and enrolled between Sept 23, 2002, and Jan 19, 2012, on one of three phase 3 COG trials in the USA and Canada were eligible for inclusion. The three COG trials were defined by risk group according to Ann Arbor stage, B-symptoms, and bulk (AHOD0431 [low risk; NCT00302003], AHOD0031 [intermediate risk; NCT00025259], or AHOD0831 [high risk; NCT01026220]). The outcomes of this study were event-free survival (death, relapse, or subsequent neoplasm) and overall survival. Cox proportional hazards models estimated survival, adjusting for disease and treatment factors both overall and in patients with mixed cellularity or non-mixed cellularity (nodular sclerosing and not-otherwise-specified) disease.Of 2155 patients enrolled on the three trials, 1907 (88·4%; 968 [50·8%] male and 939 [49·2%] female; 1227 [64·3%] non-Hispanic White) were included in this analysis. After a median follow-up of 7·4 years (IQR 4·3-10·2), older patients (aged ≥15 years) had worse unadjusted 5-year event-free survival (80% [95% CI 78-83]) than did younger patients (aged15 years; 86% [83-88]; HR 1·38 [1·11-1·71]; p=0·0038). Older patients also had worse unadjusted 5-year overall survival than did younger patients (96% [95% CI 95-97] vs 99% [98-99]; HR 2·50 [1·41-4·45]; p=0·0012). In patients with non-mixed cellularity histology, older patients had a significantly increased risk of having an event than did younger patients with the same histology (HR 1·32 [1·03-1·68]; p=0·027). Older patients with mixed cellularity had significantly worse 5-year event-free survival than did younger patients in unadjusted (77% [95% CI 65-86] for older patients vs 94% [88-97] for younger patients; HR 2·93 [1·37-6·29]; p=0·0039) and multivariable models (HR 3·72 [1·56-8·91]; p=0·0032). Overall, older patients were more likely to die than younger patients (HR 3·08 [1·49-6·39]; p=0·0025).Adolescents (≥15 years) treated on COG Hodgkin lymphoma trials had worse event-free survival and increased risk of death compared with children (15 years). Our findings highlight the need for prospective studies to examine tumour and host biology, and to test novel therapies across the age spectrum.National Institutes of Health, St Baldrick's Foundation, and Lymphoma Research Foundation.

The U.S. National Library of Medicine and Department of Homeland Security assembled subject matter experts (SMEs) for the Toxic Chemical Syndrome Definitions and Nomenclature Workshop. The SMEs at this meeting identified a lack of research evaluating the effectiveness of field recognition of toxidromes to guide treatment. They suggested that mnemonics may be helpful for remembering and recognizing toxidromes and further, that rapid toxidrome recognition, through use of a mnemonic or otherwise, leads to rapid action and urgent intervention.(1) Determine if published studies demonstrate HPs can learn and recall hazardous materials (hazmat) toxidromes. (2) Determine if Healthcare Professionals (HPs) can learn mnemonics for muscarinic and nicotinic toxidromes during the Advanced Hazmat Life Support (AHLS) Provider Course (PC) and recall these cholinergic mnemonics when retested years later. Our hypothesis is HPs can learn these mnemonics and recall them up to four years later.We analyzed results of HPs who completed AHLS PC pre-tests and post-tests during their initial AHLS PC between March 1, 2007 and March 1, 2010, and then, within four years, took either an online retest or a pre-test for a second AHLS PC. We compared pre- and post-test answers for questions regarding muscarinic and nicotinic mnemonics to assess if HPs can learn these mnemonics during an initial AHLS PC and then recall these mnemonics later, during retesting. We compared the percentage of HPs who correctly identified each cholinergic mnemonic on the pre-test, post-test, and retest using McNemar's test for paired, nominal data. We searched six literature databases to see if there were any previous similar studies.Our literature search found no similar published studies. The mean time to re-testing was 3.6 years (SD 0.8 year). The percentage of respondents correctly answering the question for the muscarinic toxidrome was 53% on the pre-test, 100% on the post-test, and 75% on the retest. The percentage of respondents correctly answering the nicotinic toxidrome question was 52% on the pre-test, 100% on the post-test, and 77% on the retest.All studied healthcare professionals learned the cholinergic toxidrome mnemonics during their initial AHLS PC. Mnemonic recall declined somewhat on retesting; however, recall was evident in 75-77% of retest takers compared to their pre-test results up to four years earlier, a statistically significant difference (

Background Motion correction is mandatory for the functional Fourier decomposition magnetic resonance imaging (FD-MRI) of the lungs. Therefore, it is important to evaluate the quality of various image-registration algorithms for pulmonary FD-MRI and to determine their impact on FD-MRI outcome. Purpose To evaluate different image-registration algorithms for FD-MRI in functional lung imaging. Material and Methods Fifteen healthy volunteers were examined in a 1.5-T whole-body MR scanner (Magnetom Avanto, Siemens AG) with a non-contrast enhanced 2D TrueFISP pulse sequence in coronal view and free-breathing (acquisition time 45 s, 250 images). Three image-registration algorithms were used to compensate the spatial variation of the lungs (fMRLung 3.0, ANTs, and Elastix). Quality control for image registration was performed by edge detection (ED), quotient image criterion (QI), and dice similarity coefficient (DSC). Ventilation, perfusion, and a ventilation/perfusion quotient (V/Q) were calculated using the three registered datasets. Results Average computing times for the three image-registration algorithms were 1.0 ± 1.6 min, 38.0 ± 13.5 min, and 354 ± 78 min for fMRLung, ANTs, and Elastix, respectively. No significant difference in the quality of motion correction provided by different image-registration algorithms occurred. Significant differences were observed between fMRLung- and Elastix-based perfusion values ​​of the left lung as well as fMRLung- and ANTs-based V/Q quotient of the right and the entire lung ( P Conclusion The mandatory motion correction for functional FD-MRI of the lung can be achieved through different image-registration algorithms with consistent quality. However, a significantly difference in computing time between the image-registration algorithms still requires an optimization.

Psychological targeting describes the practice of extracting people's psychological profiles from their digital footprints (e.g. their Facebook Likes, Tweets or credit card records) in order to influence their attitudes, emotions or behaviors through psychologically informed interventions at scale. We discuss how the increasingly blurred lines between public and private information, and the continuation of the outdated practices of notice and consent, challenge traditional conceptualizations of privacy in the context of psychological targeting. Drawing on the theory of contextual integrity, we argue that it is time to rethink privacy and move beyond the questions of who collects what data to how the data are being used. Finally, we suggest that regulations of psychological targeting should be accompanied by a mindset that fosters (1) privacy by design to make it easy for individuals to act in line with their privacy goals, as well as (2) disclosure by choice, to allow individuals to freely decide whether and when they might be willing to forsake their privacy for better service.

In the Netherlands and in Belgium, a political debate emerged regarding the possibility of euthanasia and assisted suicide (EAS) for older adults who experience their lives as completed and no longer worth living, despite being relatively healthy. This mini-review aimed to (1) present an overview of the terms used to denote this phenomenon as well as their definitions and to (2) explore how the underlying experiences are interpreted by the study authors. A systematic search was performed in Web of Science, MEDLINE, PsycINFO, and CINAHL, yielding 35 articles meeting the selection criteria. We selected empirical, English-language articles published in peer-reviewed journals. Participants had to have a first-person experience of the phenomenon or be assessed for it, or have a third-person experience of the phenomenon. Results show that the terms tiredness of life (ToL) and weariness of life (WoL) were used most frequently, also in the broader literature on suicidal expressions across the life span. Many studies mentioned operational definitions or synonyms rather than theoretical definitions. Moreover, inside the EAS debate, the term ToL was more common, its definition incorporated death wishes, and it was regularly framed existentially. Outside of this debate, the phenomenon was generally considered as a part of suicidal ideation distinct from death wishes, and its experience was often associated with underlying psychopathology. We discuss the need to establish consensus definitions and conclude that only a multidimensional view may be suitable to capture the complex nature of the phenomenon. ispartof: FRONTIERS IN PSYCHOLOGY vol:12 ispartof: location:Switzerland status: published

Family-owned businesses (FOBs) face unprecedented challenges in the wake of COVID-19. New revenue sources, workplace health and safety issues and an urgent need to drive both internal and customer-facing systems online all require quick and effective responses.This article explores how a skilled mediator can assist FOBs in reimagining themselves for the post COVID-19 environment. ‘There is no doubt that it is around the family and the home that all the greatest virtues … are created, strengthened and maintained.’ –Winston Churchill ‘Change or Die.’ – Alan Deutschman

The simple view of the classical phytoplankton–zooplankton–fish food chain (CFC) has been replaced by a more complex framework, integrating microbial compartments (microbial food web, MFW). Few studies considered all components of the pelagic MFW in freshwaters and mostly are from temperate regions. We investigated carbon partitioning in the CFC and the MFW in an Amazonian floodplain system and analyzed the strength of interactions among components through structure equation modeling. We hypothesized that (i) MFW contributes highly to total plankton biomass throughout the year; and (ii) all plankton communities increase in biomass during low water, increasing the role of trophic interactions. We collected 30 subsurface samples (nutrients and plankton communities). MFW predominated over CFC in carbon biomass, and plankton components and their interactions changed according to the contrasting water level. Because phosphorus can be a potentially limiting resource for strict primary producers, higher biomass and a more complex MFW occurred during low water. We concluded that hydrology is a key factor shaping biotic interactions during low-water periods, and that MFW plays a key role in floodplain lakes, being potential mixotrophy an important strategy for phytoplankton.

Objective: Perseverative cognition (PC) is the repeated or long-term activation of the cognitive representation of psychological stressors and is associated with prolonged stress including somatic and mental consequences. Hence, PC might represent a cognitive process linking mental and somatic pathology, but current research on this link is limited by investigating healthy samples, markers of somatic disease, and single disorders. The present study explored the importance of PC for different mental and somatic disorders in psychiatric patients. Methods: Data from 260 naturalistic psychiatric outpatients were used. Psychiatric diagnoses were based on structured clinical interviews. Somatic diseases were assessed using a well-validated questionnaire and were clustered into (cardio)vascular and immune/endocrine diseases. PC was operationalized using the Perseverative Thinking Questionnaire (PTQ). Results: Multiple regression complemented with relative importance analyses showed that the PTQ total and subscale scores were associated with the presence of mood disorders, addiction, and anxiety. Unexpectedly, no relatively important associations were found between the PTQ and autism spectrum disorder, attention-deficit/hyperactivity disorder, or somatic disease. Conclusions: Our data complement previous work linking PC to stress-related mental disorders but question its immediate role in neurodevelopmental and somatic disorders. Targeting PC in the treatment of mood disorders and perhaps also in addiction seems promising.Key words: psychiatric disorder, somatic disorder, perseverative cognition, repetitive negative thinking, stress response.

Advances in the collection, storage, and processing of large amounts of user data have given rise to psychological targeting, which we define as the process of extracting individuals’ psychological characteristics from their digital footprints in order to target them with psychologically-informed interventions at scale. In this chapter, we introduce a two-stage framework of psychological targeting consisting of (1) psychological profiling and (2) psychologically-informed interventions. We summarize the most important research findings in relation to the two stages and discuss important methodological opportunities and pitfalls. To help researchers make the most of the opportunities, we also provide practical advice on how to deal with some of the potential pitfalls. Finally, we highlight ethical opportunities and challenges and offer some suggestions for addressing these challenges. If done right, psychological targeting has the potential to advance our scientific understanding of human nature and to enhance the well-being of individuals and society at large.

Rationale and Objectives To use an automatic computed tomography (CT) dose monitoring system to analyze the institutional chest and abdominopelvic CT dose data as regards the updated 2017 American College of Radiology (ACR) diagnostic reference levels (DRLs) based on water-equivalent diameter (Dw) and size-specific dose estimates (SSDE) to detect patient-size subgroups in which CT dose can be optimized. Materials and Methods All chest CT examinations performed between July 2016 and April 2017 with and without contrast material, CT of the pulmonary arteries, and abdominopelvic CT with and without contrast material were included in this retrospective study. Dw and SSDE were automatically calculated for all scans using a previously validated in-house developed Matlab software and stored into our CT dose monitoring system. CT dose data were analyzed as regards the updated ACR DRLs (size groups: 21–25 cm, 25–29 cm, 29–33 cm, 33–37 cm, 37–41 cm). SSDE and volumetric computed tomography dose index (CTDIvol) were used as CT dose parameter. Results Overall, 30,002 CT examinations were performed in the study period, 3860 of which were included in the analysis (mean age 62.1 ± 16.4 years, Dw 29.0 ± 3.3 cm; n = 577 chest CT without contrast material, n = 628 chest CT with contrast material, n = 346 CT of chest pulmonary, n = 563 abdominopelvic CT without contrast material, n = 1746 abdominopelvic CT with contrast material). Mean SSDE and CTDIvol relative to the updated DRLs were 43.3 ± 26.4 and 45.1 ± 27.9% for noncontrast chest CT, 52.3 ± 23.1 and 52.0 ± 23.1% for contrast-enhanced chest CT, 68.8 ± 29.5 and 70.0 ± 31.0% for CT of pulmonary arteries, 41.9 ± 29.2 and 43.3 ± 31.3% for noncontrast abdominopelvic CT, and 56.8 ± 22.2 and 58.8 ± 24.4% for contrast-enhanced abdominopelvic CT. Lowest dose compared to the DRLs was found for the Dw group of 21–25 cm in noncontrast abdominopelvic CT (SSDE 30.4 ± 21.8%, CTDIvol 30.8 ± 21.4%). Solely the group of patients with a Dw of 37–41 cm undergoing noncontrast abdominopelvic CT exceeded the ACR DRL (SSDE 100.3 ± 59.0%, CTDIvol 107.1 ± 63.5%). Conclusions On average, mean SSDE and CTDIvol of our institutional chest and abdominopelvic CT protocols were lower than the updated 2017 ACR DRLs. Size-specific subgroup analysis revealed a wide variability of SSDE and CTDIvol across CT protocols and patient size groups with a transgression of DRLs in noncontrast abdominopelvic CT of large patients (Dw 37–41 cm).

Germline mutations in

OBJECTIVES: The aim of this study is to explore the contribution of genetically driven cardiometabolic risk factors for development of carotid arterial thickening in patients with type 2 diabetes.METHODS: In total, 12 genetic risk scores for blood pressure, blood lipids and glycaemic traits were constructed. The genetic risk scores were tested for association with carotid intima-media thickness and plaques in patients with type 2 diabetes ( n = 401) and in non-diabetic individuals ( n = 648) and for association with glucose levels in two population-based cohorts ( n = 1328 and n = 6161).RESULTS: In patients with type 2 diabetes, the genetic risk scores for pulse pressure were positively associated with plaque formation ( β = 0.036 ± 0.01 standard deviation/allele, p = 0.003). The genetic risk score for diastolic blood pressure was negatively associated with carotid intima-media thickness ( β = -0.037 ± 0.01 standard deviation/allele, p = 0.005), although not significant after correction for multiple testing ( p CONCLUSION: Genetic loci for pulse pressure are associated with plaque formation among patients with type 2 diabetes, suggesting an underlying genetic contribution to arterial stiffening and atherosclerosis.

Researchers and practitioners have found that telepractice is an effective means of increasing access to high-quality services that meet children’s unique needs and is a viable mechanism to deliver speech–language services for multiple purposes. We offer a framework to facilitate the implementation of practices that are used in direct speech–language therapy into parent training and coaching. We overlay the use of telepractice onto parent training and coaching to provide a framework that guides the conversion of practices used in direct service to parent training and coaching programs that can be used via telepractice. We include recommendations for addressing common challenges to providing parent training and coaching via telepractice with an example of the framework’s application in Early Intervention. Using this framework, speech–language pathologists can combine telepractice with direct services by teaching and coaching parents in the use of strategies to improve their children’s communication skills.

Magnetic proxy methods are effective tools for detecting anthropogenic heavy metal pollution of the environment. In this study we investigated the viability of using this method in an area of a complex setting where natural geogenic input, interfering land-use, and multiple different industries affect the magnetic signal. For this purpose, we took surface (N = 70) and core (N = 18) samples from an ~80 km2 area in the south-eastern Nile delta that was partly flooded before construction of a major dam, with overlapping agricultural, residential (urbanization and land reclamation), and multiple industrial activities. Using ICP-MS we characterized the spatial pollution pattern and found enrichments in seven potentially toxic heavy metals; Cu, Zn, Pb, As, Sb, Cd, and Hg, located near industrial hotspots, with highly varying pollution levels, high concentrations in the upper soil and clear depletion with depth. Magnetic susceptibility (ϰ) was measured in-situ at 170 sites, and on all samples. Thermomagnetic runs reveal that magnetite and Ti-rich titanomagnetite control the magnetic signal. Despite industrial activities are predominantly located in more sandy areas, and ϰ is found to be strongly related to spatial lithological variation, the magnetic results reasonably outline the industrial areas and show elevated ϰ levels around drains where pollutants are discharged and redistributed by irrigation. In most of these locations, ϰ decreases with depth in parallel with the pollution level, and there is a moderate correlation of ϰ with the pollution load index for the topsoil values of the core samples normalized to their bottom values. Despite the area's complexity, the spatial ϰ pattern matches reasonably well with the chemistry data of cores located in the vicinity of the main industrial spots. Therefore, also for this complex setting, time-efficient ϰ mapping provides a helpful tool as a qualitative approach for detecting key features of the spatial distribution of pollutants, which will be useful for supporting a better-targeted chemical sampling.

To evaluate machine learning (ML) to detect chest CT examinations with dose optimization potential for quality assurance in a retrospective, cross-sectional study. Three thousand one hundred ninety-nine CT chest examinations were used for training and testing of the feed-forward, single hidden layer neural network (January 2016–December 2017, 60% male, 62 ± 15 years, 80/20 split). The model was optimized and trained to predict the volumetric computed tomography dose index (CTDIvol) based on scan patient metrics (scanner, study description, protocol, patient age, sex, and water-equivalent diameter (DW)). The root mean-squared error (RMSE) was calculated as performance measurement. One hundred separate, consecutive chest CTs were used for validation (January 2018, 60% male, 63 ± 16 years), independently reviewed by two blinded radiologists with regard to dose optimization, and used to define an optimal cutoff for the model. RMSE was 1.71, 1.45, and 1.52 for the training, test, and validation dataset, respectively. The scanner and DW were the most important features. The radiologists found dose optimization potential in 7/100 of the validation cases. A percentage deviation of 18.3% between predicted and actual CTDIvol was found to be the optimal cutoff: 8/100 cases were flagged as suboptimal by the model (range 18.3–53.2%). All of the cases found by the radiologists were identified. One examination was flagged only by the model. ML can comprehensively detect CT examinations with dose optimization potential. It may be a helpful tool to simplify CT quality assurance. CT scanner and DW were most important. Final human review remains necessary. A threshold of 18.3% between the predicted and actual CTDIvol seems adequate for CT quality assurance. • Machine learning can be integrated into CT quality assurance to improve retrospective analysis of CT dose data. • Machine learning may help to comprehensively detect dose optimization potential in chest CT, but an individual review of the results by an experienced radiologist or radiation physicist is required to exclude false-positive findings.

Background To evaluate the detection rate and image quality in CT-body-packer-screening at different radiation-dose levels and to determine a dose threshold that enables a reliable detection of incorporated body packs and incidental findings with a maximum of dose saving. Materials and methods We retrospectively included 27 individuals who underwent an abdominal CT with automated exposure control due to suspected body packing. CT images were reconstructed at different radiation-dose levels of 50%, 10, 5% and 1% using iterative reconstructions. All 135 CT reconstructions were evaluated by three independent readers. Reviewers determined the presence of foreign bodies and evaluated the image quality using a 5-point ranking scale. In addition, visualization of incidental findings was assessed. Results A threshold of 5% (effective dose 0.11 ± 0.07 mSv) was necessary to correctly identify all 27 patients with suspected body packing. Extensive noise insertion to a dose level of 1% (0.02 ± 0.01 mSV) led to false-positive solid cocaine findings in three patients. Image quality was comparable between 100 and 50%. The threshold for correct identification of incidental findings was 10% of the initial dose (effective dose 0.21 ± 0.13 mSv). Conclusions Our results indicate that dose of abdominal CT for the detection of intracorporeal cocaine body packets can be markedly reduced to up to 5% of the initial dose while still providing sufficient image quality to detect ingested body packets. However, a minimum effective dose of 0.21 mSv (10% of initial dose) seems to be required to properly identify incidental findings.

Hashimoto's Encephalopathy (HE) is a rare form of autoimmune encephalopathy associated with Hashimoto's thyroiditis in which patients experience cognitive impairment and various neurologic symptoms. We present a case of a young female that presented to the emergency department with urinary retention, and was ultimately diagnosed with HE. Examination was significant for direction-changing and vertical nystagmus (direction-changing nystagmus describes a phenomenon where the fast beat changes with the direction of gaze), hyperreflexia, clonus, and Babinski and Hoffman's reflexes (all upper motor neuron (UMN) signs). Her symptoms improved with high dose intravenous steroid administration. To our knowledge, urinary retention in the presence of other UMN signs has not been reported in association with HE; nor has this patient's type of nystagmus. Emergency physicians should be aware of this condition and can play an important role by considering it when neurologic findings are not explained by infectious, toxic, metabolic, or structural etiologies. Although relatively rare, if detected and treated early HE can have a good prognosis.

Methyleugenol--a natural constituent of herbs and spices--is hepatocarcinogenic in rodent models. It can form DNA adducts after side-chain hydroxylation and sulfation. We previously demonstrated that human sulfotransferases (SULTs) 1A1 and 1A2 as well as mouse Sult1a1, expressed in Salmonella target strains, are able to activate 1'-hydroxymethyleugenol (1'-OH-ME) and 3'-hydroxymethylisoeugenol (3'-OH-MIE) to mutagens. Now we investigated the role of these enzymes in the formation of hepatic DNA adducts by methyleugenol in the mouse in vivo. We used FVB/N mice [wild-type (wt)] and genetically modified strains in this background: Sult1a1 knockout (ko), transgenic for human SULT1A1/2 (tg) and the combination of both modifications (ko-tg). Methyleugenol (50mg/kg body mass) formed 23, 735, 3770 and 4500 N (2)-(trans-methylisoeugenol-3'-yl)-2'-deoxyguanosine adducts per 10(8) 2'-deoxyribonucleosides (dN) in ko, wt, ko-tg and tg mice, respectively. The corresponding values for an equimolar dose of 1'-OH-ME were 12, 1490, 12 400 and 13 300 per 10(8) dN. Similar relative levels were observed for the minor adduct, N (6)-(trans-methylisoeugenol-3'-yl)-2'-deoxyadenosine. Thus, the adduct formation by both compounds was nearly completely dependent on the presence of SULT1A enzymes, with human SULT1A1/2 producing stronger effects than mouse Sult1a1. Moreover, a dose of 0.05 mg/kg methyleugenol (one-fourth of the estimated average daily exposure of humans) was sufficient to form detectable adducts in humanized (ko-tg) mice. Although 3'-OH-MIE was equally mutagenic to 1'-OH-ME in Salmonella strains expressing human SULT1A1 or 1A2, it only formed 0.14% of hepatic adducts in ko-tg mice compared with an equimolar dose of 1'-OH-ME, suggesting an important role of detoxifying pathways for this isomer in vivo.

Great attention has been paid to chloropropanols like 3-monochloro-1,2-propanediol and the related substance glycidol due to their presence in food and concerns about their toxic potential as carcinogens. The other chloropropanols 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol have been found in certain foods, but occurrence data are generally limited for these compounds. 1,3-dichloro-2-propanol has the most toxicological relevance showing clear carcinogenic effects in rats possibly via a genotoxic mechanism. The dietary exposure to 1,3-dichloro-2-propanol is quite low. Calculated "Margins of Exposure" values are above 10,000. It is concluded that the 1,3-dichloro-2-propanol exposure is of low concern for human health. The toxicology of 2,3-dichloro-1-propanol has not been adequately investigated. Its toxicological potential regarding hepatotoxic effects seems to be lower than that of 1,3-dichloro-2-propanol. Limited data show that 2,3-dichloro-1-propanol occurs only in trace amounts in food, indicating that exposure to 2,3-dichloro-1-propanol seems to be also of low concern for human health. The dietary 2-monochloro-1,3-propanediol burden appears to be lower than that of 3-monochloro-1,2-propanediol. An adequate risk assessment for 2-monochloro-1,3-propanediol cannot be performed due to limited data on the toxicology and occurrence in food. This article reviews the relevant information about the toxicology, occurrence and dietary exposure to the chloropropanols 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol.

In order to quantify the relative bioavailability of glycidol from glycidyl fatty acid esters in vivo, glycidyl palmitoyl ester and glycidol were orally applied to rats in equimolar doses. The time courses of the amounts of glycidol binding to hemoglobin as well as the excretion of 2,3-dihydroxypropyl mercapturic acids were determined. The results indicate that glycidol is released from the glycidyl ester by hydrolysis and rapidly distributed in the organism. In relation to glycidol, there was only a small timely delay in the binding to hemoglobin for the glycidol moiety released from the ester which may be certainly attributed to enzymatic hydrolysis. In both cases, however, an analogous plateau was observed representing similar amounts of hemoglobin binding. With regard to the urinary excretion of mercapturic acids, also similar amounts of dihydroxypropyl mercapturic acids could be detected. In an ADME test using a virtual double tag (3H, 14C) of glycidyl palmitoyl ester, a diverging isotope distribution was detected. The kinetics of the 14C-activity reflected the kinetics of free glycidol released after hydrolysis of the palmitoyl ester. In view of this experimental data obtained in rats, it is at present justified for the purpose of risk assessment to assume complete hydrolysis of the glycidyl ester in the gastrointestinal tract. Therefore, assessment of human exposure to glycidyl fatty acid ester should be regarded as an exposure to the same molar quantity of glycidol.

Methyleugenol is a genotoxic carcinogen in mice and rats, the liver being the primary target tissue. Methyleugenol occurs in fennel and many herbs and spices. Furthermore, methyleugenol-containing plant extracts and chemically prepared methyleugenol are used as flavoring agents. We analyzed surgical human liver samples from 30 subjects for the presence of DNA adducts originating from methyleugenol using isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Twenty-nine samples unambiguously contained the N (2)-(trans-methylisoeugenol-3'-yl)-2'-deoxyguanosine adduct. A second adduct, N (6)-(trans-methylisoeugenol-3'-yl)-2'-deoxyadenosine, was also found in most samples, but at much lower levels, in agreement with the results from experimental models. The maximal and median levels of both adducts combined were 37 and 13 per 10(8) nucleosides (corresponding to 4700 and 1700, respectively, adducts per diploid genome). This is the first demonstration of DNA adducts formed by a xenobiotic in human liver using UPLC-MS/MS, the most reliable method available. It has been estimated for diverse rat and mouse hepatocarcinogens that 50-5500 adducts per 10(8) nucleosides are present after repeated treatment at the TD50 (daily dose that halves the probability to stay tumor-free in long-term studies). We conclude that the exposure to methyleugenol leads to substantial levels of hepatic DNA adducts and, therefore, may pose a significant carcinogenic risk.

Acrolein is an alpha,beta-unsaturated aldehyde formed by thermal treatment of animal and vegetable fats, carbohydrates and amino acids. In addition it is generated endogenously. As an electrophile, acrolein forms adducts with gluthathione and other cellular components and is therefore cytotoxic. Mutagenicity was shown in some in vitro tests. Acrolein forms different DNA adducts in vivo, but mutagenic and cancerogenous effects have not been demonstrated for oral exposure. In subchronic oral studies, local lesions were detected in the stomach of rats. Systemic effects have not been reported from basic studies. A WHO working group established a tolerable oral acrolein intake of 7.5 mu g/kg body weight/day. Acrolein exposure via food cannot be assessed due to analytical difficulties and the lack of reliable content measurements. Human biomonitoring of an acrolein urinary metabolite allows rough estimates of acrolein exposure in the range of a few mu g/kg body weight/day. High exposure could be ten times higher after the consumption of certain foods. Although the estimation of the dietary acrolein exposure is associated with uncertainties, it is concluded that a health risk seems to be unlikely.

Fatty acid esters of 3-chloropropane-1,2-diol (3-MCPD) and glycidol are a newly identified class of food process contaminants. They are widespread in refined vegetable oils and fats and have been detected in vegetable fat-containing products, including infant formulas. There are no toxicological data available yet on the 3-MCPD and glycidol esters, and the primary toxicological concern is based on the potential release of 3-MCPD or glycidol from the parent esters by lipase-catalyzed hydrolysis in the gastrointestinal tract. Although 3-MCPD is assessed as a nongenotoxic carcinogen with a tolerable daily intake (TDI) of 2 μg/kg body weight (bw), glycidol is a known genotoxic carcinogen, which induces tumors in numerous organs of rodents. The initial exposure estimates, conducted by Federal Institute for Risk Assessment (BfR) under the assumption that 100% of the 3-MPCD and glycidol are released from their esters, revealed especially that infants being fed commercial infant formula could ingest harmful amounts of 3-MCPD and glycidol. However, the real oral bioavailability may be lower. As this gives rise for toxicological concern, the currently available toxicological data of 3-MCPD and glycidol and their esters are summarized in this review and discussed with regard to data gaps and further research needs.

Triphenyltin (TPT) is an organotin compound (OTC) previously widely used as an antifouling agent in paints applied in the marine environment, a fungicide, and as an agricultural pesticide. In female aquatic invertebrates, certain OTCs induce the so-called imposex, an abnormal induction of male sex characteristics. OTC-induced environmental endocrine disruption also occurs in fish and mammals and a number of in vivo and in vitro studies have argued that OTCs may act through inhibition of the aromatase enzyme. In vivo studies supporting the aromatase inhibition hypothesis in mammals are lacking. Recently, the causal relationship between inhibition of aromatase and imposex was questioned, suggesting aromatase independent mechanisms of action for this phenomenon. We conducted a comprehensive investigation to identify the most sensitive window of exposure to TPTCl and to examine the effects of pre- and postnatal exposure on postnatal development in rats. The results on brain and gonadal aromatase activity obtained from offspring of dams exposed to 2 mg TPTCl/kg bw are reported here. Female and male offspring rats were exposed to 2 mg TPTCl/kg bw/d in utero from gestation day 6 through lactation until weaning on PND 21, or from gestation day 6 until termination at adulthood. Male offspring were sacrificed from PND 58 and female offspring at first estrus after PND 58. Pre- and postnatal TPT exposure clearly affected brain and gonadal aromatase activity in a sex-dependent fashion. While brain aromatase activity was significantly increased on PND 21 and at adulthood in female offspring, male offspring exhibited a significant decrease in brain aromatase activity only at adulthood. Ovarian aromatase activity was unaffected at both time points investigated. In contrast, testicular aromatase activity was significantly increased in males on PND 21 and significantly decreased at adulthood independent from the duration of treatment. The results of the present study confirm our previously reported observations regarding sex-dependent differences in sexual development after TPT exposure with the male rat being more susceptible to disturbances through this endocrine active compound than the female. We conclude that TPT administered during the particularly vulnerable period of development can affect aromatase activity in rats.

Aim To evaluate the implementation of the updated computed tomography (CT) diagnostic reference levels (DRLs) from the German Federal Office for Radiation Protection into clinical routine using an automatic CT dose monitoring system. Methods and materials CT radiation exposure was analysed before and after implementing the updated national DRLs into routine clinical work in 2016. After the implementation process, institutional CT protocols were mapped to the anatomical regions for which DRLs were provided. Systematically, protocols that exceeded the thresholds were optimised and analysed in detail. The CT radiation output parameters analysed were volumetric CT dose index (CTDIvol) and dose–length product (DLP). Three radiologists evaluated subjective image quality using a three-point Likert scale. Results The study included 94,258 CT series (from 27,103 CT examinations) in adult patients performed in 2016. When averaged over all body regions with available DRL, institutional CTDIvol/DLP values were always below the DRLs (65.2±32.9%/67.3±41.5% initially; 59.4±32%/60.5±39.9% after optimisation). Values exceeding the national DRLs were found for pelvis (n=268; CTDIvol 107.7±65.7%/DLP 106.3±79.3%), lumbar spine (n=91; 160.8±74.7%/175.2±104.1%), and facial bones (n=527; 108±39%/152.7±75.7%). After optimisation, CTDIvol and DLP were 87.9±73%/87.8±80.8% for the pelvis, 67.8±33.2%/74.5±50.6% for the lumbar spine and 95.1±45.8%/133.3±74.6% for the viscerocranium. Conclusion An automatic CT dose monitoring system enabled not only comprehensive monitoring of a DRL implementation process but can also help to optimise radiation exposure.