bluuebunny/crossref_metadata_2025 huggingface dataset:
Flash Flood Measurement and Early Warning System to Remote Perilous Locations Based on Global System for Mobile and Embedded System
Authors: Selvaraju S. , Ramani R. , Valarmathy S.
Published: April 2019

Human life saving is taking prominent role in the society, Unfortunately some of people meet accident every day at any time in various incidents. Here the accident happen due to flash flood which is rapidly changing in a river, leads to ultimate damages to the people lives and their
properties at most of time in perilous locations like waterfall, River bridge and residing areas, which are in the vicinity of the river. Predominantly the people are gathering to visit the waterfall across the river and peripatetic on the riverbank or inside the river during slow water flow,
some times it leads to fatality of people who are inside the river due to flash flood, since it can't be predictable in earlier. The proposed system is providing a solution to save the people lives under this kind of circumstances. The system has transmitting processor unit must be installed
at least minimum of certain kilometers away from the perilous location to which the information about the flash flood parameters like flood velocity, volume metric flow, flood level rise per unit time and time consumption to arrive remote location for making awareness among the people peripatetic
in side or any hazardous zone of the river. Here the big foot sensor working under ultrasonic principle is suggested to measure the above flood parameter and send to the Transmitting processor unit, which estimates the arrival time by the flood to reach the remote risky location. The processed
data send to the receiver unit located at remote perilous location for making early sound and visualization alert of flood parameters on the large size screen. So that the people acquire adequate time to reach safe zone. The Transmitting processor unit starts to send this information to the
receiver unit installed on both side of riverbank, if the flash flood parameter crosses the dangerous level. The sound volume is programmed to be changed gradually according to the rate of flood parameters.
Atrial Fibrillation: A Novel Risk Factor for No-Reflow Following Primary Percutaneous Coronary Intervention
Authors: Kaya Adnan , Keskin Muhammed , Tatlisu Mustafa Adem , Uzman Osman , Borklu Edibe , Cinier Goksel , Yildirim Ersin , Kayapinar Osman
Published: April 2019

There is a lack of evidence regarding the association of atrial fibrillation (AF) and no-reflow (NR) phenomenon in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (pPCI). A total of 2452 patients with STEMI who underwent pPCI were retrospectively investigated. After exclusions, 370 (14.6%) patients were in the AF group and 2095 (85.4%) were in the No-AF group. Patients with a thrombolysis in myocardial infarction flow rate <3 were defined as having NR. Patients in the AF group were older and had higher 3-vessel disease rates (24.1% vs 18.9%; P = .021) and lower left ventricular ejection fraction (45.4 [11.7] vs 48.7 [10.5%]; P < .001). No-reflow rates were higher in the AF group than in the No-AF group (29.1% vs 11.8%; P < .001). According to multivariable analysis, AF (odds ratio: 1.81, 95% confidence interval: 1.63-2.04, P < .001), age, Killip class, anterior myocardial infarction, diabetes mellitus, chronic kidney disease, stent length, and smoking were independent predictors of NR following pPCI. Atrial fibrillation is a quite common arrhythmia in patients with STEMI. Atrial fibrillation was found to be an independent predictor of NR in the current study. This effect of AF on coronary flow rate might be considered as an important risk factor in STEMI.
Risk tolerance during conflict: Evidence from Aleppo, Syria
Authors: Mironova Vera , Mrie Loubna , Whitt Sam
Published: April 2019

When war breaks out, how important are risk preferences to explaining why some individuals stay in conflict zones while others take flight? We examine risk tolerance among rebel combatants and civilians in Aleppo, Syria using a variation of the Eckel-Grossman Choice Game. Field work in Syria was conducted in 2013–14 with a total of 232 participants to include both Syrian civilians and active rebel fighters in Aleppo and Idlib Province, as well as among Syrian refugees in neighboring Turkey. Compared to Syrians in other locations, people in rebel-held territory of Aleppo, both combatants and non-combatants, are significantly more risk tolerant. We consider possible explanations for elevated risk preferences in Aleppo based on self-selection, adaptive learning, a sense of self-efficacy to affect future outcomes, conflict-related grievances, and in-group solidarity. Our analysis suggests that self-selection based on access to resources and a strong sense of self-efficacy may explain higher propensity for risk-taking. Overall, our results speak to a plausible sorting mechanism during conflict where risk averse individuals select out of conflict, while highly risk tolerant individuals are more prone to discount the inherent dangers of remaining in conflict zones. Our results provide new micro-level explanation for why some societies become mired in conflict traps involving highly risk tolerant fighting communities.
From Class Politics to Classed Politics
Authors: Jarness Vegard , Flemmen Magne Paalgard , Rosenlund Lennart
Published: April 2019

Questions of political conflict have always been central to class analysis; changing political fault lines were a key argument in the debates about the ‘death of class’. The ensuing ‘cultural turn’ in class analysis has shown how class continues to shape lives and experience, though often in new ways. In this article, we bring this mode of analysis to the political domain by unpacking how a multidimensional concept of class – based on the ideas of Bourdieu – can help make sense of contemporary political divisions. We demonstrate that there is a homological relation between the social space and the political space: pronounced political divisions between ‘old’ politics related to economic issues and ‘new’ politics related to ‘post-material values’ follow the volume and composition of capital. Importantly, the left/right divide seems more clearly related to the divide between cultural and economic capital than to the class hierarchy itself.
The Rhetoric of Recessions: How British Newspapers Talk about the Poor When Unemployment Rises, 1896–2000
Authors: McArthur Daniel , Reeves Aaron
Published: April 2019

Recessions appear to coincide with an increasingly stigmatising presentation of poverty in parts of the media. Previous research on the connection between high unemployment and media discourse has often relied on case studies of periods when stigmatising rhetoric about the poor was increasing. We build on earlier work on how economic context affects media representations of poverty by creating a unique dataset that measures how often stigmatising descriptions of the poor are used in five centrist and right-wing British newspapers between 1896 and 2000. Our results suggest stigmatising rhetoric about the poor increases when unemployment rises, except at the peak of very deep recessions (e.g. the 1930s and 1980s). This pattern is consistent with the idea that newspapers deploy deeply embedded Malthusian explanations for poverty when those ideas resonate with the economic context, and so this stigmatising rhetoric of recessions is likely to recur during future economic crises.
‘Rise of the rest’: As hype and reality
Authors: Zarakol Ayşe
Published: April 2019

The past decade has been characterised (among other things) by the emergence of a discourse about the ‘Rise of the Rest’. (Some) non-Western states have been described as ‘rising powers’ capable of agency in the international system and as potential partners for the West in global governance. This stands in contrast to a more traditional narrative that saw the non-West primarily as a source of international problems and a developmental project. Does this discursive shift signify a historic reversal in how the non-West understood by the West? The answer is complicated. In this article, I argue that the hype about ‘rising powers’ in Western policy circles following the Global Financial Crisis of 2007–2008 had little relation to an ‘objective’ analysis of actual structural shifts in favour of ‘the Rest’ and was more akin to a financial bubble, with speculation driving perceptions of ‘rising powers’. I also show that the ‘rising powers’ literature is better located within the broader (and long-standing) debate about the decline of the United States, and should be read more as a manifestation of American anxieties and hopes than as informing us about the choices or the motivations of the ‘rising powers’. Ironically, however, the Western hype nevertheless has helped along a structural shift that is under way, first by partly moulding reality in that direction (especially in the form of financial decisions), but more importantly by freeing non-Western powers (for better or worse) from their internalised cages of perceived inferiority and lack of agency in the modern international order.
State, power and global order
Authors: Rosenboim Or
Published: April 2019

This article examines the evolution of international thought through the notion of ‘political space’. It focuses on two important domains of international politics, the nation-state and the global, to reflect on spatial categories in the discipline of International Relations (IR). Since its inception, the concept of the nation-state has dominated mainstream IR theory. Yet an investigation of how international order has been theorized over IR’s first century shows that this era has also been defined by globalist visions of political order. Nowadays, globalization is sometimes seen as the apex of the historical interplay of particularity and universality. The progression towards global political and economic order, however, is today undermined by the resurgence of state-centric political nationalism which seeks to challenge the legitimacy of the global political space. By examining how past international thinkers including Alfred Zimmern, Barbara Ward, Hans Morgenthau, E. H. Carr and John Herz, imagined and interpreted the relations of space and politics in the national and global spheres, this article suggests that spatial thinking offers an insightful approach for theorizing international relations. The article argues that the global and national spaces attain their political meanings through divisions as well as interactions and connections. The focus on divisions, exemplified in the writings of Barbara Ward, helps to make sense of the modus operandi of power in the national and global political spaces by investigating differences, tensions and instability.
Proton Pump Inhibitor Suppression of Calcium Absorption Presenting as Respiratory Distress in a Patient with Bilateral Laryngeal Paralysis and Hypocalcemia
Authors: Zaya Ninef E. , Woodson Gayle
Published: April 2019

We report an unusual case of hypocalcemia and respiratory distress related to acid-suppressive therapy. The patient was a 50-year-old woman with bilateral laryngeal paralysis and hypoparythyroidism resulting from a thyroidectomy performed more than 30 years previously. She required large doses of calcium supplementation to maintain a normal calcium level. Her airway had been marginally adequate. A few weeks prior to presentation, she began to experience increasing dyspnea. Examination was suggestive of laryngopharyngeal reflux, and she was started on a therapeutic trial of esomeprazole 40 mg twice daily. Three days later, she presented to the emergency room with airway distress. Laboratory studies indicated that the patient had hypocalcemia. The esomeprazole was discontinued, and she was treated with intravenous calcium; her symptoms resolved. We attribute the airway distress to tetany in synkinetically reinnervated laryngeal adductor muscles. We recommend that acid-suppressive therapy should be used with caution in patients with hypoparathyroidism or hypocalcemia.
HLA-B27-Associated Bilateral Ménière Disease
Authors: Rawal Shamila G. , Thakkar Kunal H. , Ziai Kasra , Santi Peter A. , Djalilian Hamid R.
Published: April 2019

We describe 2 cases of bilateral Ménière disease with features resembling autoimmune inner ear disease in patients who were found to be carriers of human leukocyte antigen (HLA) B27. For immunohistochemical analysis, mouse inner ear sections were used as the tissue substrate for reaction with serum. Both patients demonstrated an increased immunofluorescence reaction compared with a normal control. We suggest that an antibody-mediated mechanism may be responsible for HLA-B27–associated Ménière disease.
Cerebellopontine Angle Ganglionic Hamartoma: Case Report
Authors: Ahmad Sidrah M. , Garcia Fernando , Sataloff Robert T.
Published: April 2019

Cerebellopontine angle (CPA) ganglionic hamartomas are rare. We present a case of a 49-year-old woman who presented with left-sided hearing loss of more than 4 years’ duration and vertigo since childhood. Magnetic resonance imaging revealed a mass on the intracanalicular segment of cranial nerve VIII on the left side, consistent with acoustic schwannoma. She opted for observation of the tumor. The patient returned 21 months after the initial evaluation with new-onset left facial weakness. At this time, a working diagnosis of facial nerve neuroma was made. The lesion was excised, and pathology confirmed a diagnosis of left-sided CPA ganglionic hamartoma. Otolaryngologists should be familiar with this uncommon tumor and include it in the differential diagnosis of CPA lesions.
A Preliminary Theoretical Model of Hydrodynamics in the Inner Ear
Authors: Yu Vivian M. , Strykowski Paul J. , Odland Rick M.
Published: April 2019

Head movement should create a transient pressure imbalance across the membranous inner ear. We used basic concepts of fluid dynamics to develop a theoretical model of the inner ear. According to this model, two contiguous fluidic systems—the perilymphatic system and the endolymphatic system—are in hydrostatic equilibrium across a compliant membrane. Our model demonstrates that changes in resistance or compliance in one system results in a transient distortion of the membranous inner ear until equilibrium between the two systems is restored. The concept of hydrodynamic pressure changes in the inner ear has received little attention, but it may represent a new approach to understanding the inner ear and treating inner ear diseases.
Double Bilobed Radial Forearm Free Flap for Anterior Tongue and Floor-of-Mouth Reconstruction
Authors: Ko Alvin B. , Lavertu Pierre , Rezaee Rod P.
Published: April 2019

We describe what is, to the best of our knowledge, the first use of a double bilobed radial forearm free flap in reconstructive surgery of the tongue and floor of the mouth following bilateral tumor resection. Our patient was a 78-year-old man who had experienced tumor recurrence in the anterior floor of the mouth after previous resection and radiotherapy. Eleven weeks postoperatively, the patient could extend his tongue to his hard palate and past his mandibular alveolus anteriorly. Within 6 months, he was able to tolerate an oral diet of soft food and exhibited understandable speech quality. Although the use of a single bilobed radial forearm flap is widely used after hemiglossectomy, our double bilobed modification extends this technique to anterior tongue and floor-of-mouth defects. This technique provides adequate bulk while allowing for depth of a ventral sulcus that will minimize tethering of the tongue and reduce oral incompetence. We recommend that this technique be included in the armamentarium of any reconstructive head and neck cancer surgeon.
Sensitivity and Specificity of Rapid Antigen Detection Testing for Diagnosing Pharyngitis in the Emergency Department
Authors: Sarikaya Sezgin , Aktaş Can , Ay Didem , Çetin Asli , Celikmen Ferudun
Published: April 2019

Acute pharyngitis in adults is primarily a viral infection; only about 10% of cases are of bacterial etiology. Most cases of bacterial pharyngitis are caused by group A beta-hemolytic streptococci (GABHS). One laboratory method for the diagnosis of GABHS is rapid antigen diagnostic testing (RADT), which can be processed during an emergency department visit and which has become a popular alternative to throat swab cultures. We conducted a study to define the sensitivity and specificity of RADT, using throat culture results as the gold standard, in 100 emergency department patients who presented with symptoms consistent with streptococcal pharyngitis. We found that RADT had a sensitivity of 68.2% (15 of 22), a specificity of 89.7% (70 of 78), a positive predictive value of 65.2% (15 of 23), and a negative predictive value of 90.9% (70 of 77). We conclude that RADT is useful in the emergency department when the clinical suspicion is GABHS, but results should be confirmed with a throat culture in patients whose RADT results are negative.
Laryngeal Cancer in Patients Younger than 30 Years: A Review of 99 Cases
Authors: Rutt Amy L. , Hawkshaw Mary J. , Sataloff Robert T.
Published: April 2019

Laryngeal cancer in patients younger than 30 years is uncommon. We present data on this population obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. We identified 99 patients in this age group from the SEER 17 registry, which includes data submitted from 1973 through 2003. This population was made up of 52 females and 47 males; most were white, and most were aged 25 to 29 years. Malignancies of the glottis were the most common cancers, followed by supraglottic lesions. The 5-year relative survival rate was lowest among those aged 15 to 19 years—60.1%; 5-year relative survival among those aged 20 to 24 and 25 to 29 years was 87.7 and 87.4%, respectively. The etiology of squamous cell carcinoma (SCC) in children and adolescents remains uncertain, but in the adult population, a history of smoking, drinking, and poor oral hygiene cannot be ignored. Carcinoma of the larynx in young people has been related to malignant degeneration of papillomas and to complications of radiotherapy for papillomas. Infection with the human immunodeficiency virus possibly accelerates the development of SCC in patients with significant risk factors, presumably by impairing normal immune surveillance mechanisms.
Radiologic Features of Papillary Carcinoma in the Second Branchial Cleft Cyst
Authors: Hong Yong Tae , Hong Ki Hwan
Published: April 2019

Clinically, it may be very difficult to differentiate between benign branchial cleft cyst (BCC) and malignant BCC with papillary carcinoma preoperatively. Radiological features were reviewed retrospectively between benign BCC and malignant BCC with papillary carcinoma using computed tomography (CT) and magnetic resonance (MR) images. All patients had only a mass on the right upper lateral neck without lesion in the thyroid gland. Two patients had a mass in the upper medial part of BCC on CT images and one patient showed a well-circumscribed mass in the upper portion of BCC on MR image. Two patients received BCC removal only and one patient underwent total thyroidectomy including removal of BCC. As results, most cases of papillary carcinoma in the BCC were detected incidentally after surgical resection of BCC. However, we can differentiate between benign BCC and malignant BCC with primary papillary carcinoma by carefully reviewing radiologic images before surgery.
Punjabi Orchard Farmers: An Immigrant Enclave in Rural California
Authors: Gibson Margaret A.
Published: April 2019

Examination of the adaptation patterns of Punjabi Sikh orchard farmers in rural California provides further evidence of ways in which strong ethnic enclaves help to promote rapid economic self-sufficiency among immigrant groups. The discussion emphasizes the need to consider not only the cultural traditions of group members, but also the historical context of immigration and the immigrants’ perceptions of their particular situation. The Punjabi case indicates, too, how the 1965 Immigration Act, with its preference for family reunification, has promoted the formation of immigrant enclaves.
Bahamian Labor Migration to Florida in the Late Nineteenth and Early Twentieth Centuries
Authors: Johnson Howard
Published: April 2019

In the period 1880–1920 wage-labor migration of Bahamians, unlike that of other British West Indians, was primarily to the nearby State of Florida. This article examines the economic structure of the Bahamas which, with the decline of major agricultural export staples, promoted this outward migration particularly to Miami in the early years of the twentieth century. It discusses the implications of oscillating and permanent migration for the sending area. This discussion involves a consideration of the effects of labor migration on the family and out-island agriculture and the impact of remittances on economic development in the Bahamas.
Immigration and the Earnings of Youth in the U.S.
Authors: Matta Benjamin N. , Popp Anthony V.
Published: April 2019

This article reports findings that have emerged from an effort made at statistically measuring the effects of immigration on the earnings of U.S.-born youth. The presence of immigrants arriving before 1965 has a positive impact on youth earnings. Recently arrived immigrants impact negatively, however. These results are consistent with recent findings that the skill level of immigrants arriving within the last two decades is lower relative to that of immigrants arriving earlier. The results also show that the negative effects diminish as the youth ages, reflecting skill acquisition and job mobility of the young worker into jobs less vulnerable to competition from immigrant workers.
Jewish Ethics and International Migrations
Authors: Plaut W. Gunther
Published: April 2019

Jews developed a distinct ethical approach to the question of dealing with strangers in society. Examples are provided from Jewish ethical literature to illuminate this attitude and its practice. This paper touches on the Jewish migratory experience in the last 2,000 years and their acceptance in Christian and Muslim countries. Note is taken of the concept of “refuge,” which was created by the Hebrew Bible and has had a significant influence on the Sanctuary Movement. The essay concludes with a personal observation, based on the author's life experience.
The Islamic Conception of Migration
Authors: Abu-Sahlieh Sami A. Aldeeb
Published: April 2019

This article discusses migration as viewed by classical Islamic law, a corpus of disparate juridical institutions and concepts accumulated since the seventh century which is based on two principal sources, The Qur'an and the Sunnah of Muhammad. The Qur'an; the first source of Islamic law, collects the revelation transmitted by God to Muhammad between 610 and 632 A.D., date of his death. Muslims believe that the author of this book is not Muhammad but God himself. The present text was established fifteen or twenty years after the death of Muhammad. The Sunnah of Muhammad is the second source of Islamic law. This term designates sayings, accounts and facts, called also hadiths, attributed to Muhammad, infallible model according to the Qur'an and interpreter of God's will. These hadiths are reported in many collections and in the biographies whose authenticity is often questioned.
Application of the Three Rs Principle in the Compilation of “Technical Guidance Document in Support of Directive 98/8/EC Concerning the Placing of Biocidal Products on the Market, Part I, Guidance on Data Requirements for Active Substances and Biocidal Products”
Authors: Sauer Ursula G. , Liebsch Manfred , Kolar Roman
Published: April 2019

In fulfilment of the aims of the European Union Biocidal Directive ( Directive 98/8/EC), Technical Guidance Documents are currently being compiled. Part I of these Technical Guidance Documents covers data requirements for active substances and biocidal products. The Three Rs principle has been applied in certain parts of the toxicity and ecotoxicity testing scheme for pesticides, such as testing for acute oral toxicity, skin and eye irritation, skin sensitisation, and dermal absorption. Further recommendations on how to proceed with regard to the continuing replacement, reduction and refinement of animal experiments in this field of regulatory testing are included for consideration. In this context, besides stressing the necessity to validate and accept further alternatives, emphasis is placed on providing the possibility of waiving unnecessary tests and on the continuous evaluation of whether certain tests are needed at all.
A New Mechanism of Mammalian Cell Resistance to the Toxic Effects of DNA-Binding Agents
Authors: Levina Vera , Varfolomeeva Elena , Sukhareva Eugenya , Shabalina Elena , Drobchenko Eugeny , Filatov Michael
Published: April 2019

The phenomenon of active dissociation of the noncovalently binding vital dye Hoechst 33342 from DNA in living cells (DNA clearing) is described. Step-by-step selection with increasing concentrations of the dye resulted in a series of rodent cell lines that were resistant to the toxic action of Hoechst 33342. Some of the lines exhibited enhanced dissociation of the bisbenzimidazole dye–DNA complex. Two cell lines from this group (AA8HoeR-7 and LHoeR-3) were analysed in detail and compared with a Syrian hamster tumour cell line, a typical example of mdr-1-mediated multidrug-resistant cell lines. The markedly enhanced level of DNA clearing in AA8HoeR-7 and LHoeR-3 cells leads to high cellular resistance to the toxic effect of Hoechst 33342 and cross-resistance to mitomycin C, a minor-groove alkylating agent in clinical use. Our results suggest that DNA clearing is one of the mechanisms of multidrug resistance in tumour cells.
Activities of Glutathione S-Transferase and Glutathione Peroxidases Related to Diet Quality in an Aphid Predator, the Seven-spot Ladybird, Coccinella septempunctata L. (Coleoptera: Coccinellidae)
Authors: Nielsen Søren Achim , Hauge Mikael S. , Nielsen Frederik H. , Toft Søren
Published: April 2019

Larvae of Coccinella septempunctata were reared on three aphid diets, consisting of pure Rhopalosiphum padi, pure Metopolophium dirhodum, and an equal mix of these aphid species. In the pupal stage, the activities of three detoxifying enzyme systems — glutathione S-transferase (GST) with 1-chloro-2,4-dinitrobenzene as substrate, glutathione peroxidase with hydrogen peroxide as substrate (GSH-Px[H2O2]), and glutathione peroxidase with tert-butyl hydroperoxide as substrate (GSH-Px[TBH]) — were assayed. Growth rate, measured as the total protein content of the pupae, was significantly higher in the mixed-diet group than in the R. padi group, whereas that of the M. dirhodum group was intermediate. GST showed lower activity in larvae on a pure R. padi diet and a mixed aphid diet than on a pure M. dirhodum diet, whereas the variation in GSH-Px[TBH] was independent of diet. GSH-Px(H2O2) showed a significantly higher activity in the R. padi group than in the M. dirhodum group, whereas that of the mixed-diet group was intermediate. Thus, feeding on the low-quality aphid, R. padi, inhibited GST and activated GSH-Px(H2O2). The induction of GSH-Px[H2O2] indicated elevated oxidative stress. This may have been caused by toxic compounds in the R. padi.
Surface-adhering Human Leucocytes: An In Vitro Model for Cytotoxicity Testing of Fluids
Authors: Nygren Håkan , Braide Magnus , Eriksson Cecilia , Yahyapour Noushin
Published: April 2019

A rapid screening method was developed for assessment of the toxic effects of fluid materials on the respiratory burst response of polymorphonuclear neutrophils (PMNLs). The method was used to detect adverse effects of peritoneal dialysis (PD) fluids. Intoxication of the respiratory burst response attenuates the bacterial killing capacity of PMNLs, and increases the sensitivity of patients to peritoneal infection. Capillary blood was taken from healthy donors, placed in drops on commercially available titanium pieces, and incubated in a humidified chamber at 37°C for up to 1 hour. The blood was rinsed off with saline, and the adhering cells were characterised by immunofluorescence by using antibodies directed against specific cell-differentiation antigens. A majority (> 95%) of the adhering leucocytes were PMNLs. The surface expression of selectins was down-regulated after 30 minutes, and the expression of integrins was down-regulated after blood exposure for 1 hour. NADPH-oxidase activity of the adhering cells was stimulated by f-MLP peptide and by opsonised zymosan. The zymosan-induced activation showed a lag-phase after 1 hour, consistent with the down-regulated expression of integrin. The zymosan-stimulated enzyme activity was used as an indicator of the cytotoxicity of PD fluids. NADPH-oxidase activity was inhibited by PD fluids with a pH of 5.7 and by heat-sterilised PD fluids. The results were compared with data obtained by using isolated circulating cells and cells from peritoneal dwell fluid.
Toxicological Investigation of Soils with the Solid-phase Flash Assay: Comparison with Other Ecotoxicological Tests
Authors: Pöllumaa Lee , Kahru Anne , Eisenträger Adolf , Reiman Rain , Maloveryan Alla , Rätsep Annely
Published: April 2019

A new direct-contact toxicity test, the solid-phase flash assay, which utilises photobacteria in direct contact with soil particles during the exposure, was evaluated on four soil samples. Samples HTNT1 and HTNT2 originated from former military sites in Germany, and were highly contaminated with nitroaromatics (approximately 20g/kg), lead and polycyclic aromatic hydrocarbons. Samples LMKW1 and LMKW2, from bioremediation stacks in Germany, were mainly contaminated with mineral oils. The solid-phase flash assay was applied to soil-water slurries, and the results were compared with the toxicity data for soil-water extracts obtained by using various conventional ecotoxicological tests, in which photobacteria, crustaceans, protozoa and algae were used as test organisms. The LMKW1 and LMKW2 samples were not toxic (EC20 > 12.5%) according to all the tests applied, except for the Photobacterium phosphoreum conventional luminescence-inhibition test for LMKW1 (15-minute EC20 = 5.4%). The HTNT1 and HTNT2 samples were toxic according to all the tests applied, with the majority of EC20 values being lower than 1%. The solid-phase flash assay (1 minute of extraction and 30 seconds of exposure time) gave comparable results to the conventional tests. Therefore, this flash assay could be applied as a fast screening test in parallel with conventional toxicity tests that use soil 24-hour extracts. The flash assay results will be ready by the start of the conventional assays, and could serve as range-finders for these slower and more expensive tests.
Local Irritation/Corrosion Testing Strategies: Extending a Decision Support System by Applying Self-Learning Classifiers
Authors: Zinke Stephan , Gerner Ingrid
Published: April 2019

Procedures have been established and tested for the extension of a decision support system (DSS) for the prediction of the local irritation/corrosion potential of chemicals by using self-learning classifiers. The different approaches (decision trees, distances examinations in a multidimensional space, k-nearest neighbour method) have been implemented, tested and evaluated independently. A combination of all of the established extension approaches was also developed and tested. Self-learning classifiers are constructed “automatically” by a computer, i.e. they are not derived by a human expert, and thus they can be constructed with minimal effort. The classifiers presented here extend the existing DSS in a manner that increased significantly the predictive power of the extended system. However, automatically calculated results of self-learning classifiers are produced by a machine, and a machine is incapable of explaining the toxicological relevance of the results obtained. Thus, these results must be accepted, despite an inability to prove their reliability. Only the mathematical correctness of the method and the prediction rates for suitable test cases can lend some credibility to predictions produced by a computer calculating on a self-learning basis. This may not be adequate for regulatory hazard assessment purposes.
The Three Rs: A Journey or a Destination?
Authors: Richmond Jon
Published: April 2019

It is an honour to have been asked to follow in the footsteps of Professor Russell (1) and deliver the FRAME Annual Lecture. In doing so, I am not speaking in any official capacity. I am speaking as myself: someone who has had a 30-year association with medicine and the biological sciences, who has had more time and reason than most to reflect upon the changes that have taken place during that period, and to think about how things may develop in the future. The views expressed tonight are based upon, and represent, my personal experience, expectations and aspirations.
Indirect Cytotoxicity of Dental Materials: A Study with Transwell Inserts and the Neutral Red Uptake Assay
Authors: Babich Harvey , Sinensky Mayer C.
Published: April 2019

A modification of the Transwell insert methodology was evaluated by using the neutral red uptake (NRU) assay in a cytotoxicity test. The Transwell insert methodology was developed to assess the biocompatibility of solid materials used in dentistry and, when initially designed, used the release of radiochromium (51Cr) in the cytotoxicity assay. Another aim of this study was to evaluate different exposure regimes with which to assess cytotoxicity. The exposure regimes included: a 1-hour exposure in buffer followed by a 24-hour incubation in growth medium; a 2-hour exposure in buffer followed by a 24-hour incubation in growth medium; a 24hour exposure in serum-limited medium; and a 24-hour exposure in a serum-sufficient medium. The bioindicator target was the Smulow-Glickman (S-G) human gingival cell line and the biomaterials were dental restoratives. The Transwell insert methodology with the NRU cytotoxicity assay as the cytotoxicity endpoint was effective in differentiating the potencies of the dental restoratives; a 2-hour exposure in buffer and a 24-hour exposure in serum-limited medium were the exposure regimes that most clearly differentiated the test agents according to their potencies. The sequence of cytotoxicity of the dental restoratives to the S-G cells was Vitremer > Ketac-Molar Aplicap > Flow-It.
The Importance of the Prediction Model in the Validation of Alternative Tests
Authors: Worth Andrew P. , Balls Michael
Published: April 2019

An overview is presented of the validation process adopted by the European Centre for the Validation of Alternative Methods, with particular emphasis on the central role of the prediction model (PM). The development of an adequate PM is considered to be just as important as the development of an adequate test system, since the validity of an alternative test can only be established when both components (the test system and the PM) have successfully undergone validation. It is argued, however, that alternative tests and their associated PMs do not necessarily need to undergo validation at the same time, and that retrospective validation may be appropriate when a test system is found to be reliable, but the case for its relevance remains to be demonstrated. For an alternative test to be considered “scientifically valid”, it is necessary for three conditions to be fulfilled, referred to here as the criteria for scientific relevance, predictive relevance, and reliability. A minimal set of criteria for the acceptance of any PM is defined, but it should be noted that required levels of predictive ability need to be established on a case-by-case basis, taking into account the inherent variability of the alternative and in vivo test data. Finally, in view of the growing shift in emphasis from the use of standalone alternative tests to alternative testing strategies, the importance of making the PM an integral part of the testing strategy is discussed.
Cytotoxicity of the MEIC Reference Chemicals in Antioxidant-enriched Rat Hepatoma-derived Fa32 cells
Authors: Dierickx Paul J. , Smit Claudia , Scheers Ellen M.
Published: April 2019

Since vitamin E increases the antioxidant status of cells, its influence on cytotoxicity was investigated. The neutral red uptake (NRU) inhibition effects of 39 MEIC reference chemicals were measured after treatment of rat hepatoma-derived Fa32 cells in the presence of vitamin E for 30 minutes. The results were quantified in terms of the NI50, the concentration of test compound required to reduce the NRU by 50%. Sodium chloride was the only chemical that was more toxic in the presence of vitamin E. This effect was related to the concentration of vitamin E in the cell culture medium. A vitamin E dose-related response was also observed for the decreased toxicity of paracetamol and caffeine. Glutathione levels were slightly increased in the presence of vitamin E, which could contribute to the protective effect of vitamin E. Of the remaining chemicals, 50% were less toxic in the presence of vitamin E, but the correlation with the acute human toxicity data of the MEIC study was not improved. The results imply that reactive oxygen species interfere with the toxicity of a high proportion of toxic chemicals. The assay described provides a quick and easy method for checking whether reactive oxygen species contribute to the toxicity of a chemical.
The Use of Bootstrap Resampling to Assess the Variability of Draize Tissue Scores
Authors: Worth Andrew P. , Cronin Mark T.D.
Published: April 2019

The acute dermal and ocular effects of chemicals are generally assessed by performing the Draize skin and eye tests, respectively. Because the animal data obtained in these tests are also used for the development and validation of alternative methods for skin and eye irritation, it is important to assess the inherent variability of the animal data, since this variability places an upper limit on the predictive performance that can be expected of any alternative model. The statistical method of bootstrap resampling was used to estimate the variability arising from the use of different animals and time-points, and the estimates of variability were used to determine the maximal extent to which Draize test tissue scores can be predicted.
Losartan Decreases Glomerular Filtration Rate in Isolated Perfused Porcine Slaughterhouse Kidneys
Authors: Stahl Katja , Fehrenberg Claudia , Neew-Galuschka Evelyn , Krössin Thomas , Kaczmarczyk Gabriele
Published: April 2019

We investigated whether Losartan, an angiotensin II (Ang II) AT1, receptor antagonist, decreases renal vascular resistance (RVR) and increases glomerular filtration rate (GFR) in isolated perfused porcine slaughterhouse kidneys (11 control experiments and 11 Losartan experiments with 7.5mg Losartan in the preservation solution and 100μg/minute Losartan infused during perfusion). With perfusion, plasma renin activity (PRA) increased markedly from 3 ± 1 to 90 ± 17 ng Ang I/ml/h (control), and from 4 ± 1 to 70 ± 8 ng Ang I/ml/h (Losartan), plasma Ang II increased from 86 ± 63 to 482 ± 111 pg/ml (control), and from 73 ± 42 to 410 ± 91 pg/ml (Losartan). The GFR was decreased in Losartan experiments as compared with control experiments (5 ± 1 versus 10 ± 2 ml/min/100g kidney wt; p < 0.05). The RVR was the same in both groups (0.2 ± 0.01 mm Hg/100g kidney wt/min/ml). Tubular sodium reabsorption was decreased in Losartan experiments as compared with control experiments (0.7 ± 0.1 versus 1.4 ± 0.3 mmol/min/100g kidney wt). Overall, Losartan accentuated pathophysiological signs of acute renal failure. Although other drugs have to be investigated, these results suggest that porcine slaughterhouse kidneys could be useful as a tool for research in areas such as transplantation and intensive-care medicine.
Two In Vitro Models for Gas-Phase Exposure to Volatile Compounds
Authors: Bonsi Paola , Zucco Flavia , Stammati Annalaura
Published: April 2019

Two experimental models suitable for the screening of volatile compounds were set up. The first consisted of a glass chamber-slide with eight wells, one carrying the test compound, and the others carrying cells in monolayers. In the second model, the cells were cultured in a glass Petri dish, and the test compound was poured onto a filter lying on a glass cover-slip, supported by a metal ring. Four plant volatiles [carvacrol, S-(+)-carvone, thymol and decanal] and one essential oil (caraway oil) were chosen as test compounds. The toxicity rankings obtained with the two models were compared with that obtained in a previous study performed with the same compounds under conventional culture conditions. Differences in the toxicity ranking were observed between the conventional culture conditions and the gasphase models, confirming the importance of correct exposure conditions for the evaluation of toxicity. Both models have advantages that make them suitable as a preliminary step in the toxicity screening of volatile compounds, or for use in a test battery when combined with conventional approaches.
A Method for the In Vitro Exposure of Human Cells to Environmental and Complex Gaseous Mixtures: Application to Various Types of Atmosphere
Authors: Aufderheide Michaela , Knebel Jan W. , Ritter Detlef
Published: April 2019

The application of in vitro methods to the analysis of the effects of airborne materials is still limited, because there are no generally accepted concepts and technologies for efficiently exposing adherent growing cells to test atmospheres, especially those comprising complex mixtures of gaseous and particulate phases. The introduction of in vitro research into the field of inhalation toxicology offers a unique possibility for using human cells and tissues for pre-screening studies, thus reducing the necessity for animal experiments, and cutting the numbers of animals used in toxicological testing. We therefore developed a novel experimental concept that uses an exposure device based on the cell cultivation system CULTEX (Patent No. DE 198011763; PCT/EP99/00295). This allowed us to investigate environmental atmospheres, which were chemically and physically unmodified, in an in vitro system, by exposing the target cells directly at the air/liquid interface. The exposure device itself is small and flexible enough to be connected to a variety of aerosol-generating systems without the need for an incubator, as it fulfils all the requirements for maintaining cell viability over a defined period. The general applicability and the sensitivity of this in vitro approach for testing various generated atmospheres under the same cell-exposure conditions were demonstrated by studying dose-dependent cytotoxic effects in human lung epithelial cells exposed to air contaminated with single gases or complex mixtures, such as diesel exhaust fumes and side-stream cigarette smoke.
Evaluation of a Porcine Lens and Fluorescence Assay Approach for In Vitro Ocular Toxicological Investigations
Authors: Oriowo Olanrewaju M. , Cullen Anthony P. , Schirmer Kristin , Chou B. Ralph , Bols Niels C. , Sivak Jacob G.
Published: April 2019

Cell biology, as monitored with the fluorescent indicator dyes Alamar Blue™ and 5-carboxy-fluorescein diacetate acetoxymethyl ester (CFDA-AM), and lens optical quality, as measured with an in vitro scanning laser system, have been used to evaluate in vitro the condition of porcine lenses after being placed in a culture medium. The measurements, beginning from week one of culture, were compared statistically. Optical quality and cellular viability, as measured with either dye, were unchanged in lenses that had been maintained for 6 weeks in modified M199 medium. Some lenses were treated with 0.152J/cm2 UVB radiation, and a decline was observed after 48 hours in both optical and metabolic capabilities, as indicated by a decreased capacity of the lenses to reduce Alamar Blue. The measurements with CFDA-AM did not show complete concordance with the other indicators of lens health after UV treatment, making this dye less reliable as applied currently to lens cultures. Overall, the findings suggest that porcine lenses can be maintained for weeks in culture, and that their condition can be evaluated quantitatively by assays that probe cellular functions and optical properties. Such a system should prove valuable for in vitro ocular pharmacotoxicological research.
Long-term In Vitro Toxicity Models: Comparisons Between a Flow-cell Bioreactor, a Static-cell Bioreactor and Static Cell Cultures
Authors: Pazos Patricia , Fortaner Salvador , Prieto Pilar
Published: April 2019

In vitro long-term toxicity testing is becoming an important issue in the field of toxicology, and there is a need to develop new model systems that mimic human chronic exposure and its effects. The aim of this work was to test two long-term in vitro toxicity systems which are available, a flow-cell bioreactor (Tecnomouse) and a static cell bioreactor system (CELLine CL 6-well), and to compare them with the use of conventional cell culture flasks. A human cell line, Int 407, was exposed to cadmium chloride (CdCl2; 10–7–10–8M) for 4 weeks. Cell numbers and cell viabilities were determined by the trypan blue (TB) exclusion assay and from exclusion of propidium iodide (PI) as determined by flow cytometry; and cell viability and metabolic activity were determined by the MTT assay. In addition, total protein determination and cadmium uptake measurements were performed. The results obtained with TB and PI exclusion did not show clear differences in cell viability with increasing CdCl2 concentration. However, in the static cell-culture systems, an increase in MTT reduction was found at low concentrations of CdCl2. Expression of heat-shock protein (Hsp27 and Hsp70) increased differently, depending on the CdCl2 concentration applied and the system used. In summary, of the two bioreactors, the CELLine CL 6-well bioreactor was shown to be the more efficient system for performing long-term cytotoxicity studies. It is easy to handle, it permits the assessment of several endpoints, and sufficient replicates can be made available.
A Comparison of Ecotoxicological Tests
Authors: Botsford James L.
Published: April 2019

A simple, inexpensive and rapid method of determining toxicity by using a bacterium as the indicator organism was developed and compared with 23 other tests. The average correlation coefficient when comparing these 23 tests with the present test was 0.800, ranging from 0.580 to 0.950. Eleven of the tests were compared in detail by using 35 of the chemicals on the Multicentre Evaluation of In Vitro Cytotoxicity list of test chemicals. Comparing results from the present test with test results for these 35 chemicals with Microtox™, Biotox™, Daphnia magna, rat hepatocytes and ascites tumour cell resulted in correlation coefficients ranging from 0.871 to 0.933. Comparisons of the test data with rodent LD50 values, human lethal dose estimates from autopsies and human lethal doses obtained from the literature provided correlation coefficients ranging from 0.580 to 0.770, indicating that the test compares less favourably with these methods. This test provides data comparable to data from other ecotoxicological tests.
The Establishment of ECVAM and its Progress since 1993
Authors: Balls Michael
Published: April 2019

The background to the establishment of ECVAM in 1991 is summarised, and progress made since 1993 is briefly reviewed in relation to 12 recommendations made at the ECVAM Opening Symposium in 1994 and to statements on tests for chemicals and biologicals endorsed by the ECVAM Scientific Advisory Committee since 1997.