bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Solitary Extramedullary Plasmacytoma of the Tongue
Authors: Onal Cem , Oymak Ezgi , Uguz Aysun , Ergin Melek
Published: April 2019

Extramedullary plasmacytomas are rare malignancies. Most cases (80%) are seen in the head and neck region, where they represent 1 % of all head and neck malignancies. We report a case of an extramedullary plasmacytoma of the tongue that was treated successfully with three-dimensional conformal radiotherapy. The patient was a 50-year-old woman who was admitted to our hospital with bilateral pain and ulceration on the sides of her tongue. Findings on magnetic resonance imaging and positron-emission tomography did not demonstrate any mass within the tongue or any lymphatic or distant metastasis. A tissue biopsy identified a plasma cell neoplasm. The patient was treated with a total dose of 50 Gy delivered in 2-Gy daily fractions. After 54 months of post-treatment follow-up, she exhibited no sign of systemic myeloma or local recurrence. This case is presented not only for the rarity of the tumor type, but also for its unusual location.
Bipolar Microdebrider may Reduce Intraoperative Blood Loss and Operating Time during Nasal Polyp Surgery
Authors: Kumar Nishant , Sindwani Raj
Published: April 2019

Bleeding during endoscopic sinus surgery (ESS) can interrupt the flow of the procedure and increase the risk of complications. Advances in microdebrider design now allow for bleeding to be controlled by bipolar energy during the suctioning and shaving of polyps. We conducted a retrospective study to examine the effects of this technology on blood loss and operating times during ESS for chronic rhinosinusitis with nasal polyps (CRS+P). Our patient population was made up of 80 patients who had undergone ESS for CRS+P by the same surgeon from January 2007 through May 2008. All surgeries were performed with either the PK diego bipolar microdebrider (Gyrus ACMI, ENT Division; Bartlett, Tenn.) or a standard microdebrider. There were 40 patients in each group. The PK group was made up of 23 males and 17 females, aged 14 to 66 years (mean: 43.1), and the control group included 21 males and 19 females, aged 17 to 71 years (mean: 43.1); there were no statistically significant differences between the two groups in terms of sex and age. In addition to demographic data, the charts were reviewed for comorbidities and operative variables; the latter included blood loss, operating room (OR) time, and complications. The preoperative treatment and anesthesia protocols were similar for all patients, and all patients demonstrated a similar disease burden on imaging (mean Harvard CT stage: 3.12 for the PK group and 3.15 for the controls; p > 0.05). We found that during ESS, the PK group experienced significantly less intraoperative blood loss than did the controls (means: 86.0 and 123.0 ml, respectively; p = 0.015). In addition, the PK device was associated with significantly shorter OR times (means: 88.9 and 101.4 min, respectively; p = 0.026). There were no complications in either group. We conclude that usinga microdebrider with bipolar capabilities during ESS may offer the advantages of less blood loss and shorter operating times inpatients with nasal polyps.
Management of Head and Neck Paragangliomas: A Series of 9 Cases and Review of the Literature
Authors: Destito Domenico , Bucolo Sebastiano , Florio Alessandra , Quattrocchi Carmelo
Published: April 2019

We conducted a retrospective study of the long-term functional results of surgery for head and neck paragangliomas. Our study population was made up of 9 patients—4 men and 5 women, aged 22 to 59 years (mean: 46.6; median: 51)—who had undergone surgical excision of a head and neck paraganglioma from January 2002 through December 2006 in the ENT Department at Pugliese-Ciaccio Hospital in Catanzaro, Italy. Of the 9 paragangliomas, 4 were carotid body tumors, 2 were glomus tympanicum tumors, and 3 were glomus vagale tumors. None of the cases was bilateral or hereditary. Complete tumor resection was achieved in 8 patients; in the remaining patient, a small amount of intradural residual vagus nerve paraganglioma had to be left in situ. The internal carotid artery was preserved in all 4 resections of carotid body tumors. There was only 1 case of postoperative lower cranial nerve deficits, which occurred in a patient with a carotid body tumor. Follow-up ranged from 12 to 53 months (mean: 37.2; median: 36), and no recurrences were documented. Our small sample showed that surgical treatment of head and neck paragangliomas provided excellent tumor control with low postoperative morbidity, even in patients with large tumors. A wait-and-scan policy may be more appropriate for patients at an advanced age or who are otherwise at high surgical risk, as well as for those whose tumors have recurred following radiotherapy.
Bilateral Posterior Semicircular Canal Dehiscence in the Setting of Hallermann-Streiff Syndrome
Authors: Goddard John C. , Oliver Eric R. , Meyer Ted A.
Published: April 2019

Hallermann-Streiff syndrome, also known as oculomandibulofacial syndrome, is a rare congenital disorder affecting growth and cranial, dental, ocular, pilocutaneous, and mental development. In addition to routine audiologic testing in patients with this syndrome, high-resolution computed tomography of the temporal bones should be performed in those with documented or suspected sensorineural hearing loss. Cochlear implantation may be considered, as in other children with syndromic hearing loss and certain inner ear abnormalities, if the appropriate audiologic, psychosocial, and medical criteria are met. The current case report radiographically and clinically characterizes inner ear dysplasia in an 8-year-old patient with Hallermann-Streiff syndrome. High-resolution computed tomography of the temporal bones revealed a hypoplastic bony island between the vestibule and horizontal semicircular canals, as well as incomplete bony coverage of the posterior semicircular canal crura bilaterally. To our knowledge, this is the first report of a pediatric patient demonstrating bilateral posterior semicircular canal dehiscence.
Vocal Fold Fixation Caused by Penetration of a High-Velocity Steel Projectile
Authors: Guo Chau-Shiang , Ho Chi-Kung , Hsu Ruey-Fen
Published: April 2019

Vocal fold fixation as a result of trauma caused by a foreign body is rare. We report a unique case of vocal fold fixation caused by traumatic penetration of a shard of steel in a 31-year-old steelworker. While the patient was at work, an airborne projectile suddenly pierced his neck and entered his larynx, causing progressive hoarseness and dyspnea. Flexible laryngoscopy detected no obvious foreign body, but it did reveal that the right vocal fold had become immobile. Computed tomography revealed that a 2.5-cm sliver of steel had become impacted in the right cricoarytenoid joint, which made the arytenoid cartilage unable to rotate. An emergency tracheostomy was performed with local anesthesia to construct a functioning airway, and then rigid laryngoscopy was performed with general anesthesia. The foreign body was removed with the assistance of a microscope and microscissors. Postoperatively, the patient immediately regained control of his right vocal fold, and he experienced no permanent injury.
The Significance of Magnetic Resonance Imaging and Computed Tomography Findings in Sphenoid Sinus Agenesis
Authors: Uzun Lokman , Sagun Omer Faik , Seferoglu Bulent , Etlik Omer , Mahmutyazicioglu Kamran
Published: April 2019

Agenesis of the sphenoid sinuses is a very rarely encountered anatomic variation. Findings on magnetic resonance imaging can mislead the radiologist and clinician. Therefore, the gold standard for diagnosis is computed tomography (CT) of the paranasal sinuses. We present the case of a 28-year-old man who was admitted to our hospital with a 3-month history of headache. CT of the paranasal sinuses revealed isolated bilateral sphenoid sinus agenesis.
Aggressive Inflammatory Pseudotumor of the Maxillary Sinus and Orbit
Authors: Chong Sheldon , Teh Carren S.L. , Singh Shashinder , Seong Mun Kein , Viswaraja Subrayan
Published: April 2019

Inflammatory pseudotumor (IPT) is a rare, locally aggressive, benign neoplasm of unknown etiology. It is uncommon in the head and neck region, particularly in the paranasal sinuses. We present an unusual case of IPT of the maxillary sinus and orbit in a 27-year-old woman who presented with cheek swelling, right orbital swelling, double vision, and associated fever and trismus. Computed tomography identified a mass with radiologic features suggestive of a malignancy of the maxillary sinus and orbit; the mass extended into the infratemporal fossa, parapharyngeal space, anterior antral wall, and surrounding soft tissue. A diagnosis of IPT was established on the basis of histologic and immunohistochemical analysis, which identified a proliferation of bland spindle cells and a mixed inflammatory cell infiltrate. Despite its aggressive appearance, IPT is associated with a good prognosis. Our patient was treated successfully with a combination of surgery, steroid therapy, and methotrexate. Chemotherapeutic agents are generally reserved for recalcitrant cases.
Early Detection of Nasopharyngeal Carcinoma using IgA Anti-EBNA1 + VCA-p18 Serology assay
Authors: Romdhoni Achmad C. , Wiqoyah Nurul , Kentjono Widodo Ario
Published: April 2019

Nasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in Indonesia. Overall, it ranks fourth in males and sixth in females as the most prevalent type of cancer in that country. The data show that in the year 2011, NPC incidence was considered to be intermediate (6.2/100,000 population per year). Through histopathologic examination, about 70 to 80% of these cases were found to be type HI according to the WHO classificaton. NPC carries an excellent prognosis if treated early, but most patients presented with stage III to IV disease, which negatively affected the cure rate and increased the mortality rate. Epstein-Barr virus (EBV) IgA serology has been established as an effective marker for NPC. Therefore, biologic markers, DNA, and/or antibody-based diagnosis is needed to decrease NPC cases. A screening program needs to be developed that will identify people at high risk of NPC and those who are in the early stage of the disease. In this study, 20 samples were collected from posttherapy patients. An otolaryngologic examination, histopathology of nasopharyngeal tissue, and blood testing for serologic markers were performed. IgA anti-EBNA1 + VCA-p18 enzyme-linked immunosorbent assay showed positive impact as a tool for confirming the diagnosis of NPC, but it still has to be combined with other specific diagnostic tools for post-therapy monitoring and for determining prognosis.
Nasal Valve Surgery: Assessment of Quality of life with the Glasgow Benefit Inventory
Authors: Manickavasagam Jaiganesh , Wong Smeeta , Varabei Veronika , Raghavan Ullas
Published: April 2019

We used the IB-question Glasgow Benefit Inventory (GBI) to conduct a retrospective assessment of quality of life following nasal valve surgery. We telephoned 53 patients who had undergone open rhinoplasty for the treatment of nasal valve collapse over a 2-year period. A total of 39 patients—24 men and 15 women, aged 20 to 50 years (mean: 38)—agreed to participate and answer the questions. Follow-up ranged from 3 to 12 months (mean: 8). The spectrum of possible GBI scores ranges from −100 (maximum negative outcome) to 0 (no change) to +100 (maximum benefit); in our group, the median total score was +56 (interquartile range: +32 to +90.5) and the overall total score was +58. The three subscale components of the GBI—general benefit, physical benefit, and social benefit—were analyzed individually; the respective median scores were +46 (+21 to +71), +67 (+25 to +91.5), and +50 (+17 to + 100), and the respective overall scores were +60, +59, and +50. Based on these findings, we conclude that nasal valve surgery significantly improves quality of life.
A Rare Cause of Conductive Hearing Loss: High Lateralized Jugular Bulb with Bony Dehiscence
Authors: Barr James G. , Singh Pranay K.
Published: April 2019

We present a rare case of pediatric conductive hearing loss due to a high lateralized jugular bulb. An 8-year-old boy with a right-sided conductive hearing loss of 40 dB was found to have a pink bulge toward the inferior part of the right eardrum. Computed tomography showed a high, lateralized right jugular bulb that had a superolaterally pointing diverticulum that bulged into the lower mesotympanum and posterior external auditory meatus. It was explained to the child's parents that it is important never to put any sharp objects into the ears because of the risk of injury to the jugular vein. A high, lateralized jugular bulb with a diverticulum is a rare anatomic abnormality. Correct diagnosis of this abnormality is important so that inappropriate intervention does not occur.
Detection of CMV DNA in the Perilymph of a 6-Year-Old Boy with Congenital Cytomegalovirus Infection
Authors: Foulon Ina , Soetens Oriane , Vleurinck Leen , Gordts Frans , Leus Astrid , Naessens Anne
Published: April 2019

We present the case of a 6-year-old boy who received a cochlear implant for profound sensorineural hearing loss after being born with cytomegalovirus (CMV) infection. Even after 6 years, CMV DNA was still found in the perilymph of the cochlea. Our case shows that CMV DNA can be present in the cochlea years after congenital CMV infection, and it can explain why progressive and/or late-onset hearing loss occurs in these children.
In a Family Way? A model of family firm identity maintenance by non-family members
Authors: Vincent Ponroy Julia , Lê Patrick , Pradies Camille
Published: April 2019

Focusing on the case of a successful French pharmaceutical family firm – VetCo, we develop a process model of family firm identity maintenance by non-family members. Being the first family-owned pharmaceutical actor exclusively dedicated to animal health worldwide, VetCo has a strong family firm identity. The maintenance of this identity is remarkable, as VetCo experienced a withdrawal of the owning family when its founder suddenly passed away and, later on, when other family members disengaged from operations. Using grounded theory, we build a process model of identity maintenance that emphasizes meaning multiplicity. Specifically, we identify three main mechanisms of meaning preservation – passing on the family legacy, unifying the metaphorical family and modelling the family business – and two mechanisms of meaning connection – holding on and bridging. In elaborating theory on family firm identity maintenance, this study contributes to family business and organizational identity scholarships.
Carbaryl-induced Behavioural and Reproductive Abnormalities in the Earthworm Metaphire posthuma: A Sensitive Model
Authors: Gupta Shrawan K. , Saxena Prem N.
Published: April 2019

Carbaryl, an N-methyl carbamate insecticide, is used in India to control foliar insects, but, due to soil contamination, it also adversely affects non-target organisms such as earthworms. This paper deals with the toxic effects of carbaryl on the behavioural and reproductive profiles of the earthworm, Metaphire posthuma. Locomotion and geotaxis were significantly affected, even after a 20-minute exposure to 0.125ppm carbaryl. The hatching of cocoons was altered at 0.5ppm, whereas cocoon production was retarded even at 0.125ppm carbaryl. No cocoon production was observed at 2.0ppm carbaryl. Sperm head abnormalities were reported even at the lowest test concentration of 0.125ppm. Wavy head abnormalities were observed at 0.125ppm carbaryl, whereas at 0.25ppm and 0.5ppm, the sperm heads became amorphous and the head nucleus was turned into granules deposited within the wavy head. It is concluded that the earthworm could be used as an ecosystem model for the initial toxicity testing of environmental pollutants.
The Mouse Bioassay for Diarrhetic Shellfish Poisoning: A Gross Misuse of Laboratory Animals and of Scientific Methodology
Authors: Combes Robert D.
Published: April 2019

The UK shellfish industry has recently been affected by the statutory closure of several cockle beds, following the detection of samples causing rapid and severe reactions in the regulatory approved test for diarrhetic shellfish poisoning (DSP) toxins, the mouse bioassay (MBA). It is contended that these so-called atypical results are due to procedural artefacts of the MBA; so far, several studies have failed to identify their cause. This paper critically assesses the development, regulatory use and methodological deficiencies of the MBA. It also discusses how testing for DSP toxins could and should have been improved and made more humane by applying the Three Rs concept of Reduction, Refinement and Replacement, and by the proper validation of the test method used. It is concluded that the MBA should not have been developed for the routine screening of shellfish samples, as it has a substantially severe endpoint and is not used as part of a tiered-testing strategy with non-animal methods. Moreover, during the UK monitoring programme for DSP toxins, the assay has been used without an optimised and universal protocol, and apparently without due regard to the principles of basic scientific methodology. In view of this, the atypical results obtained for cockle samples cannot be relied on as evidence of a human health hazard. It is recommended that the use of the MBA should be discontinued as soon as possible, in favour of other methods, especially those involving non-animal techniques. In the short-term, these methods should be based on analytical chemical detection systems and the essential availability of the relevant pure toxin standards. The lack of any known toxins in samples should be taken as evidence of lack of contamination. The suitability of the existing non-animal methods needs to be assessed as a matter of urgency. It is crucial that all new methods should be properly validated, and that their acceptability for their stated purposes should be endorsed by recognised criteria and validation centres, before being recommended to, or required by, regulatory agencies. In this way, the possibility that scientifically unsuitable methods will once again be used for monitoring for the contamination of shellfish with toxins can be avoided. This gross misuse of laboratory animals and ill-judged application of science should never be allowed to occur again.
Uses of Animals and Alternatives in College and Veterinary Education at the University of California, Davis: Institutional Commitment for Mainstreaming Alternatives
Authors: Hart Lynette A. , Wood Mary W.
Published: April 2019

uses of animals in teaching for college, veterinary and medical education in the USA has sharply declined in recent decades. Economic disincentives and public discussions have diminished this use of animals, as well as the growing availability of alternative resources for teaching. In the USA, the use of live animals in teaching at the post-secondary level requires a protocol review similar to that used for research, whereas protocols are not required for the use of non-living specimens. Many outstanding alternatives have been created that supplant some uses of animals. Creating alternatives for a comprehensive biological or veterinary curriculum can best be addressed by a long-term commitment of leadership at the institutional level, leading to an incremental development of alternatives. Economic realities and the demonstration of educational results equal to, or exceeding that of the consumptive uses of animals support supplanting the more traditional methods. Committed leadership at the University of California, Davis, has facilitated the development of teaching tools and the mainstreaming of alternatives within the standard undergraduate and veterinary curriculum. The institutional culture supports these resources, and finding further solutions requiring less consumptive uses of animals. We introduce here a web-based tool providing improved access to these resources: www.vetmed.ucdavis.edu/Animal_Alternatives/main.htm .
The Revision of European Housing Guidelines for Laboratory Animals: Expectations from the Point of View of Animal Welfare
Authors: Sauer Ursula G.
Published: April 2019

The housing guidelines for laboratory animals laid down in Appendix A of the European Convention for the protection of laboratory animals ETS 123 have been taken over in an Annex of Council Directive 86/609/EEC. Article 5 of the Convention and Articles 5a and 5b in the Directive state that housing conditions for laboratory animals must be appropriate to their health and well-being and that any restriction on the extent to which an experimental animal can satisfy its physiological and ethological needs shall be limited to the absolute minimum. However, the concrete housing guidelines depicted in the Annexes are inadequate to meet these principles. In addition, for many commonly used species, such as fish and amphibians, there are no housing guidelines at all. In recognition of these deficiencies, the Council of Europe is currently revising Appendix A of the Convention. Efforts are aimed at providing animals with housing conditions that enable them to live in harmonious, stable groups, fulfil their species-specific locomotory needs and engage in meaningful activity. The European Commission intends to revise the Directive accordingly. However, legal problems remain to be overcome, before the new guidelines can actually be voted upon for inclusion in either document.
Ethical and Welfare Implications of the Acquisition and Transport of Non-human Primates for Use in Research and Testing
Authors: Prescott Mark J. , Jennings Maggy
Published: April 2019

Assessment of the ethical and welfare implications of any laboratory animal use should encompass the entire life-history of the animals concerned, including their acquisition and transport. This is particularly important in the case of non-human primates, because the acquisition of some species involves capture from the wild, inadequate husbandry, and/or lengthy, multistaged travel from the country of origin to the laboratory where they are used. Thus, non-human primates endure considerable harms even before they reach the laboratory. Despite this, the information necessary to increase awareness of, and to assess, the potential harms of acquisition and transport is not readily available. This paper highlights the ethical and welfare concerns associated with these processes and makes recommendations intended to reduce their impact on welfare. The information presented is collated from a recent report that analyses the UK trade in non-human primates for research and testing, but many of the concerns and recommendations are applicable in an international forum. The need to minimise suffering is emphasised, as is the need for critical review of the necessity and justification for all non-human primate use, a reduction in the numbers used, and the development of alternatives to replace their use.
ECOPA: The European Consensus Platform on Three Rs Alternatives
Authors: Rogiers Vera
Published: April 2019

ECOPA, the European Consensus Platform on Alternatives, is an international not-for-profit organisation, based in Belgium and complying with Belgium law. It is the only quadripartite organisation that is promoting the Three Rs at the European level. ECOPA brings together the National Consensus Platforms on alternative methods in Europe. Consensus means that all parties concerned are represented, including animal welfare, industry, academia and governmental institutions. Ecopa actually comprises 14 Member State (or future Member State) National Platforms (eight full members: the platforms of Austria, Belgium, Finland, Germany, The Netherlands, Spain, Switzerland and the UK; and six associate members: the Czech Republic, Denmark, Italy, Norway, Poland and Sweden), and has three working groups. The fields of interest of these working groups change according to the needs and actually are concerned with a) the Sixth Framework Programme of the European Commission (EC) for Research, Technological Development and Demonstration Activities, b) the EC White Paper on a Strategy for a Future Chemicals Policy, and c) the formation of educational programmes on alternative methods within the EU. ECOPA is thus uniquely placed and has huge expertise to offer to the debate around scientific and politically linked topics. It has to be considered a key stakeholder by the European Commission and Parliament. News and views of ECOPA can be found on the ECOPA website ( http://www.ecopa.tsx.org/ ), which is regularly updated.
The Use of Reconstructed Human Epidermis for Skin Absorption Testing: Results of the Validation Study
Authors: Schäfer-Korting Monika , Bock Udo , Diembeck Walter , Düsing Hans-Jürgen , Gamer Armin , Haltner-Ukomadu Eleonore , Hoffmann Christine , Kaca Monika , Kamp Hennicke , Kersen Silke , Kietzmann Manfred , Korting Hans Christian , Krächter Hans-Udo , Lehr Claus-Michael , Liebsch Manfred , Mehling Annette , Müller-Goymann Christel , Netzlaff Frank , Niedorf Frank , Rübbelke Maria K. , Schäfer Ulrich , Schmidt Elisabeth , Schreiber Sylvia , Spielmann Horst , Vuia Alexander , Weimer Michaela
Published: April 2019

A formal validation study was performed, in order to investigate whether the commercially-available reconstructed human epidermis (RHE) models, EPISKIN®, EpiDerm™ and SkinEthic®, are suitable for in vitro skin absorption testing. The skin types currently recommended in the OECD Test Guideline 428, namely, ex vivo human epidermis and pig skin, were used as references. Based on the promising outcome of the prevalidation study, the panel of test substances was enlarged to nine substances, covering a wider spectrum of physicochemical properties. The substances were tested under both infinite-dose and finite-dose conditions, in ten laboratories, under strictly controlled conditions. The data were subjected to independent statistical analyses. Intra-laboratory and inter-laboratory variability contributed almost equally to the total variability, which was in the same range as that in preceding studies. In general, permeation of the RHE models exceeded that of human epidermis and pig skin (the SkinEthic RHE was found to be the most permeable), yet the ranking of substance permeation through the three tested RHE models and the pig skin reflected the permeation through human epidermis. In addition, both infinite-dose and finite-dose experiments are feasible with RHE models. The RHE models did not show the expected significantly better reproducibility, as compared to excised skin, despite a tendency toward lower variability of the data. Importantly, however, the permeation data showed a sufficient correlation between all the preparations examined. Thus, the RHE models, EPISKIN, EpiDerm and SkinEthic, are appropriate alternatives to human and pig skin, for the in vitro assessment of the permeation and penetration of substances when applied as aqueous solutions.
Estimates for Worldwide Laboratory Animal Use in 2005
Authors: Taylor Katy , Gordon Nicky , Langley Gill , Higgins Wendy
Published: April 2019

Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs ( replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and unsubstantiated, ranging from 28–100 million. We collated data for 37 countries that publish national statistics, and standardised these against the definitions of ‘animals’, ‘purposes’ and ‘experiments’ used in European Union Directive 86/609/EEC. We developed and applied a statistical model, based on publication rates, for a further 142 countries. This yielded our most conservative estimate of global animal use: 58.3 million animals in 179 countries. However, this figure excludes several uses and forms of animals that are included in the statistics of some countries. With the data available, albeit for only a few countries, we also produced, by extrapolation, a more comprehensive global estimate that includes animals killed for the provision of tissues, animals used to maintain genetically-modified strains, and animals bred for laboratory use but killed as surplus to requirements. For a number of reasons that are explained, this more-comprehensive figure of 115.3 million animals is still likely to be an underestimate.
Introduction to the EU REACH Legislation
Authors: Grindon Christina , Combes Robert
Published: April 2019

FRAME initiatives on the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals, first proposed as a White Paper in 2001, are summarised. These initiatives considered the scientific and animal welfare issues raised by the REACH proposals, and resulted in a number of suggestions for improvement, many of which seem to have been adopted during the current progress of the legislation through the European Council and European Parliament.
Overcoming Barriers to Validation of Non-animal Partial Replacement Methods/Integrated Testing Strategies: The Report of an EPAA–ECVAM Workshop
Authors: Kinsner-Ovaskainen Agnieszka , Akkan Zerrin , Casati Silvia , Coecke Sandra , Corvi Raffaella , Negro Gianni Dal , De Bruijn Jack , De Silva Odile , Gribaldo Laura , Griesinger Claudius , Jaworska Joanna , Kreysa Joachim , Maxwell Gavin , McNamee Pauline , Price Anna , Prieto Pilar , Schubert Roland , Tosti Luca , Worth Andrew , Zuang Valerie
Published: April 2019

The use of Integrated Testing Strategies (ITS) in toxicological hazard identification and characterisation is becoming increasingly common as a method for enabling the integration of diverse types of toxicology data. At present, there are no existing procedures and guidelines for the construction and validation of ITS, so a joint EPAA WG5–ECVAM workshop was held with the following objectives: a) to investigate the role of ITS and the need for validation of ITS in the different industry sectors (pharmaceuticals, cosmetics, chemicals); b) to formulate a common definition of ITS applicable across different sectors; c) to explore how and when Three Rs methods are used within ITS; and d) to propose a validation rationale for ITS and for alternative methods that are foreseen to be used within ITS. The EPAA provided a platform for comparing experiences with ITS across different industry sectors. It became clear that every ITS has to be adapted to the product type, R&D stage, and regulatory context. However, common features of ITS were also identified, and this permitted the formulation of a general definition of ITS in a regulatory context. The definition served as a basis for discussing the needs, rationale and process of formal ITS validation. One of the main conclusions was that a formal validation should not be required, unless the strategy will serve as full replacement of an in vivo study used for regulatory purposes. Finally, several challenges and bottlenecks to the ITS validation were identified, and it was agreed that a roadmap on how to address these barriers would be established by the EPAA partners.
Computational Toxicology Approaches at the US Food and Drug Administration
Authors: Yang Chihae , Valerio Luis G. , Arvidson Kirk B.
Published: April 2019

For over a decade, the United States Food and Drug Administration (US FDA) has been engaged in the applied research, development, and evaluation of computational toxicology methods used to support the safety evaluation of a diverse set of regulated products. The basis for evaluating computational toxicology methods is multi-factorial, including the potential for increased efficiency, reduction in the numbers of animals used, lower costs, and the need to explore emerging technologies that support the goals of the US FDA's Critical Path Initiative (e.g. to make decision support information available early in the drug review process). The US FDA's efforts have been facilitated by agency-approved data-sharing agreements between government and commercial software developers. This commentary review describes former and current scientific initiatives at the agency, in the area of computational toxicology methods. In particular, toxicology-based QSAR models, ToxML databases and knowledgebases will be addressed. Notably, many of the computational toxicology tools available are commercial products — however, several are emerging as non-commercial products, which are freely-available to the public, and which will facilitate the understanding of how these programs work and avoid the “black box” paradigm. Through productive collaborations, the US FDA Center for Drug Evaluation and Research, and the Center for Food Safety and Applied Nutrition, have worked together to evaluate, develop and apply these methods to chemical toxicity endpoints of regulatory interest.
Alternatives for Lung Research: Stuck between a Rat and a Hard Place
Authors: BéruBé Kelly A.
Published: April 2019

The respiratory system acts as a portal into the human body for airborne materials, which may gain access via the administration of medicines or inadvertently during inhalation of ambient air (e.g. air pollution). The burden of lung disease has been continuously increasing, to the point where it now represents a major cause of human morbidity and mortality worldwide. In the UK, more people die from respiratory disease than from coronary heart disease or non-respiratory cancer. For this reason alone, gaining an understanding of mechanisms of human lung biology, especially in injury and repair events, is now a principal focus within the field of respiratory medicine. Animal models are routinely used to investigate such events in the lung, but they do not truly reproduce the responses that occur in humans. Scientists committed to the more robust Three Rs principles of animal experimentation ( Reduction, Refinement and Replacement) have been developing viable alternatives, derived from human medical waste tissues from patient donors, to generate in vitro models that resemble the in vivo human lung environment. In the specific case of inhalation toxicology, human-oriented models are especially warranted, given the new REACH regulations for the handling of chemicals, the rising air pollution problems and the availability of pharmaceutically valuable drugs. Advances in tissue-engineering have made it feasible and cost-effective to construct human tissue equivalents of the respiratory epithelia. The conducting airways of the lower respiratory system are a critical zone to recapitulate for use in inhalation toxicology. Three-dimensional (3D) tissue designs which make use of primary cells, provide more in vivo-like responses, based on the targeted interactions of multiple cell types supported on artificial scaffolds. These scaffolds emulate the native extracellular matrix, in which cells differentiate into a functional pulmonary tissue. When 3-D cell cultures are employed for testing aerosolised chemicals, drugs and xenobiotics, responses are captured that mirror the events in the in situ human lung and provide human endpoint data.
Where does iPS Cell Technology Leave the Promoters of the Creation and Use of Admixed Animal–Human Embryos?
Authors: Balls Michael
Published: April 2019

Breakthroughs with iPS cells make the creation of admixed embryos unnecessary and indefensible
Animals are More than Tools
Authors: Hendriksen Coenraad , Baumans Vera , Blaauboer Bas
Published: April 2019

The moral value of animals deserves greater recognition in scientific publications
Animal Experimentation: The Statistics Speak for Themselves
Authors: Balls Michael , Combes Robert D.
Published: April 2019

As a new consortium to promote animal experimentation is formed, the numbers of procedures reported to the UK Home Office continue to increase, and opportunities to replace them are not being taken
A Novel Porcine Ex Vivo Retina Culture Model for Oxidative Stress Induced by H2O2
Authors: Hurst José , Kuehn Sandra , Jashari Adelina , Tsai Teresa , Bartz-Schmidt Karl Ulrich , Schnichels Sven , Joachim Stephanie C.
Published: April 2019

Oxidative stress is a key player in many ophthalmic diseases. However, the role of oxidative stress in most degenerative processes is not yet known. Therefore, accurate and practical models are required to efficiently screen for therapeutics. Porcine eyes are closely related to the human eye, and can be obtained from the abattoir as a by-product of the food industry. Therefore, they offer excellent opportunities for the development of culture models with which to pre-screen potential therapies, while reducing the use of laboratory animals. To induce oxidative stress, organotypic cultures of porcine retina were treated with different doses of hydrogen peroxide (H2O2; 100, 300 and 500μM) for three hours. On days 3 and 8, the retinas were conserved for histological and Western blotting analyses and for evaluation of gene expression, which determined the number of retinal ganglion cells (RGCs), the activation state of glial cells, and the expression levels of several oxidative stress markers. H2O2 treatment led to a reduction in the number of RGCs and to an increase in apoptotic RGCs. In addition, a dose-dependent increase of microglia and an elevation of CD11b expression was observed. On day 3, a reduction of IL-1β, and an increase of iNOS, as well as of HSP70 mRNA were found. On day 8, an increase in TNF-α and IL-1β mRNA expression was detected. In conclusion, this ex vivo model offers an opportunity to study the molecular mechanisms underlying certain eye disorders and to test new therapeutic approaches to diminish the effects of oxidative stress.
A variable admittance control strategy for stable physical human–robot interaction
Authors: Ferraguti Federica , Talignani Landi Chiara , Sabattini Lorenzo , Bonfè Marcello , Fantuzzi Cesare , Secchi Cristian
Published: April 2019

Admittance control allows a desired dynamic behavior to be reproduced on a non-backdrivable manipulator and it has been widely used for interaction control and, in particular, for human–robot collaboration. Nevertheless, stability problems arise when the environment (e.g. the human) the robot is interacting with becomes too stiff. In this paper, we investigate the stability issues related to a change of stiffness of the human arm during the interaction with an admittance-controlled robot. We propose a novel method for detecting the rise of instability and a passivity-preserving strategy for restoring a stable behavior. The results of the paper are validated on two robotic setups and with 50 users performing two tasks that emulate industrial operations.
Synergistic role of susceptibility-weighted imaging with diffusion-weighted imaging and magnetic resonance angiography in the evaluation of acute arterial stroke
Authors: Rai Santosh PV , Sanyal Pulastya , Pai Shivananda , Achappa Basavaprabhu , Madi Deepak , MR Pavan
Published: April 2019

Objective

This study was performed to investigate whether diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) are more effective than conventional imaging modalities for evaluation of stroke and selection of candidates for thrombolytic therapy.

Methods

Eighty patients who presented within 12 hours of onset of symptoms of brain ischemia underwent 1.5T magnetic resonance imaging. DWI and SWI were compared with conventional sequences (T1, T2, and fluid-attenuated inversion recovery [FLAIR]) and time-of-flight magnetic resonance angiography (TOF-MRA) to assess factors that affect stroke management and prognosis.

Results

The volume of brain tissue showing hyperintensity was significantly greater than that showing diffusion restriction in patients with a >6-hour symptom onset. The hypointensity sign (susceptibility sign) on SWI showed a sensitivity of 66.7%, specificity of 87.5%, positive predictive value of 88.9, and negative predictive value of 63.6 compared with TOF-MRA. Micro-hemorrhagic foci were significantly associated with 27-mL infarcts on DWI (sensitivity, 71.4%; specificity, 85.0%). Patients with DWI–SWI mismatch showed better responses to thrombolytics. FLAIR–DWI mismatch helped to assess the time of stroke onset.

Conclusion

DWI and SWI should be part of the routine imaging protocol in patients with acute stroke and serve as a decision-making tool for selection of patients for thrombolytic therapy.
The price of outsourcing: A content analysis of the effects of early deadlines on the sports section in The Oklahoman
Authors: Ketterer Stan , McGuire John , Murray Ray
Published: April 2019

Newspapers have begun outsourcing their printing to cut costs, and this study employs a content analysis to examine its effects on the award-winning sports section of The Oklahoman. Before outsourcing, it was a typical metropolitan daily covering all important games with few missing late scores. Afterward, problems associated with earlier deadlines and printing in another city included late delivery, incomplete or missing game coverage, and numerous missing scores. These problems led to complaints that the publisher acknowledged. The results indicate outsourcing has costs that management should consider before employing it. Although the newspaper followed economic principles, these problems could damage its reputation.
The effect of simultaneous exposure to cigarette smoke and noise on distortion product otoacoustic emissions in rats
Authors: Habybabady Raheleh Hashemi , Mohammadi Mahdi , Mortazavi Seyed Bagher , Khavanin Ali , Mirzaei Ramazan , Malvajerdi Mehdi Sadeghi
Published: April 2019

Cigarette smoking is a possible risk factor for hearing loss. However, the impact of simultaneous exposure to noise and smoke on hearing has remained controversial. This study investigated the combined effect of exposure to cigarette smoking and noise on hearing loss. Three groups of male Wistar rats (275 ± 25 g) were subjected to white noise (102 ± 0.5 dB), cigarette smoking (20 cigarettes), and both cigarette smoking and noise for 8 h and 10 days inside the exposure chamber. The control group was exposed to neither noise nor smoke. Distortion product otoacoustic emissions (DPOAE) were measured before any intervention, and it was repeated 1, 7, and 21 days after the last exposure. One-day postexposure to noise, cigarette smoking, and both cigarette smoking and noise, the mean of DPOAE amplitudes decreased significantly ( p < 0.05) between, respectively, 5.7–30.7, 1.5–7.5, and 5.2–32.6 dB within the frequency range of 4620–9960. Temporal DPOAE change in rats exposed to noise or both cigarette smoking and noise was not significantly different ( p > 0.05). DPOAE amplitudes returned to the baseline values in the group subjected to smoking 21 days postexposure. The most permanent change was observed in rats exposed to both cigarette smoking and noise. Accordingly, simultaneous subacute exposure to noise and cigarette smoking increases the effect of noise on permanent hearing loss. Therefore, smoking workers exposed to noise might be at a greater risk of developing hearing loss, and it is recommended that authorities in charge take note of this evidence.
Le jugement professoral : Jugement de classe, jugement scolaire et théorie du « capital culturel ». Retour sur « les catégories de l’entendement professoral » (Bourdieu et de Saint Martin, 1975)
Authors: Glevarec Hervé
Published: April 2019

La question du jugement des enseignants semble une dimension centrale de toute analyse des faits de reproduction sociale et plus encore des faits de reproduction scolaire qui en sont une dimension constitutive. Les appréciations scolaires sont-elles une forme dissimulée d’un jugement de classe et par-là l’expression et un moyen de la reproduction sociale ? En 1975, P. Bourdieu et M. de Saint Martin ont soutenu cette hypothèse en produisant une analyse qui visait à montrer que les « catégories de l’entendement professoral », nommément d’un professeur de philosophie, étaient des catégories du discours dominant et des moyens de la perpétuation de la structure sociale. Un retour critique sur cette démonstration permet de voir que les auteurs ont, d’une part, privilégié le « classement social » au détriment du « classement scolaire » et, d’autre part, assimilé jugement social (de classe) et jugement scolaire dans la notion de « capital culturel ». Cette mise au jour du jugement sociologique se veut donc à la fois une archéologie de la recherche sociologique et une argumentation en faveur de la distinction du « savoir » et du « capital culturel ».
Institutional ethnography as a unique tool for improving health systems
Authors: Rowland Emily , Manogaran Myuri , Bourgeault Ivy Lynn
Published: April 2019

Qualitative research in the health system has made tremendous developments in the last decade to better understand patient experiences. What is often overlooked, are the influences that the internal structures, policies and people have on the individuals that use health services. Institutional ethnography is a qualitative approach that aims to capture the social organization of "everyday life" at various system levels. An institutional ethnographic framework was applied to two research studies exploring how families experience care in neonatal intensive care units. Data were collected to develop a deep understanding of the social contexts that exist within institutional boundaries. This paper provides evidence that how care is organized and delivered can significantly influence patient experiences, perceptions and ultimately health outcomes. Adopting institutional ethnographic techniques as a common research method is a valuable tool for health leaders seeking to understand and develop recommendations for health system reform.
Hooking-Up and Sexual Victimization on Campus: Examining Moderators of Risk
Authors: Sutton Tara E. , Simons Leslie Gordon , Tyler Kimberly A.
Published: April 2019

Hooking-up among college students presents an increased risk of sexual victimization, perhaps due to increased contact with potential perpetrators in a risky context. However, little work has examined factors that might increase the risk of victimization associated with hooking-up, and few studies examine victimization among both men and women. To address this gap in the literature, we utilize data from 702 college women and 677 college men to explore childhood sexual abuse, family violence, sexual minority (SM) status, and problematic alcohol use as potential moderators of the association between hooking-up and three forms of sexual victimization: coerced, incapacitated, and forced. Results of regression analyses indicate several significant interactions and significant main effects. For example, SM men and women were each at an increased risk of forced and incapacitated victimization when hook-up frequency was high compared with non-SM students.