bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Way of Home Appliances Control Using Smartphone with Secure Efficient Authentication Protocol
Authors: Jeyapadmini J. , Iyswarya K. , Kiruthika G. S. , Muthuramalingam R. , Gayathri M.
Published: April 2019

As the technology grows rapidly the level of sophistication also increases day by day. One of the biggest challenges faced today is the energy conservation with the growth in technology. The conservation of energy starts with the control of the appliance, ranging from home to large
industry. Appliances control at home is a way where the energy wasted can be reduced to a minimum. This can be done with the help of smartphones. As the world is shrinks into the smartphones, everything becomes handy. An idea of home appliance control with the smartphones makes it easy for
the user to control the appliances inside the home. As every smartphone is provided with the Bluetooth technology, it's tranquil to control the devices inside the home premises. Also with the help of SEAP protocol and the sensors, a secure way of controlling the appliances is made. An Android
application for the smartphone is been developed, which is used in the control of the home appliances. Thus the user can control the appliances from their place and conserve the energy without much work done.
Air Pressure Test on Concrete with Nano-Cement
Authors: Carmichael Jemimah M. , Arulraj Prince G.
Published: April 2019

Nanotechnology is an emerging area of research that has received a lot of attention for its ability to make use of the unique properties of nano-sized materials. The grain size of the nano particles will be in the order of 10–9 m (1–100 nm). Due to the very small
particle size and extremely large specific surface area, nano particles have same remarkable properties. The use of nano materials for making concrete is of recent origin. Addition of nano materials in concrete can lead to significant improvements in the strength and durability of concrete.
For nuclear power plants, concrete with high compressive strength, high split tensile strength, low porosity and high density are required. An attempt has been made to increase the compressive and split tensile strength of concrete by replacing a portion of cement with nano cement. M20, M30,
M40 and M50 grades of concrete were cast. For each of these mixes, 10%, 20%, 30%, 40% and 50% of cement was replaced with nano- cement. Nano-cement was made by grinding the commercially available 53 grade pozzolona cement in the ball grinding mill. A scanning electron microscope was used to
determine the particle size of the nano-cement produced. A hollow cylinder of the concrete was made with concrete containing nano materials. The Air pressure test was carried at on hardened concrete and the results were compared with that of normal cement concrete. The safe internal pressure
for M50 concrete with 50% replacement of cement with nano-cement was found to be 13.3 kg/cm2, which 31.6% higher than that of the normal M50 concrete.
Numerical Analysis of the Hybrid Photonic Crystal Fiber and Single Mode Fiber/Fiber Bragg Grating Sensor for Simultaneous Measurement of Temperature and Strain
Authors: de Sousa Fabio Barros , de Sousa Fiterlinge Martins , de Oliveira Jorge Everaldo , de Oliveira Lelis Araujo , da Luz Fabricio Pinho , Oliveira Jackson Moreira , Costa Marcio Benedito Caldas , Paschoal Waldomiro , da Silva Junior Carlos Alberto Brito , Costa Marcos Benedito Caldas
Published: April 2019

In this paper we investigate the performance of a Fiber Bragg Grating (FBG) as a strain-optic and temperature sensor, using the Coupled Mode Theory (CMT) and the Transfer Matrix Method (TMM), through numerical simulation in an interrogation system with Single-Mode Fiber (SMF) and Photonic
Crystal Fiber (PCF). Parameters such as sensitivity, bandwidth, peak power, peak wavelength and side-lobes power, were analyzed through the Bragg wavelength change depending on the simultaneous variation of strain and temperature. The FBG sensor proposed suffered thermal variation 25 °C
to 200 °C and of strain of 0 μs to 1000 μs, excellent linearity was obtained for the variation of the Bragg wavelength with differences of 0.7 nm for each 50 °C and 0.245 nm for each 200.
GRADE-Based Recommendations for Surgical Repair of Nonruptured Abdominal Aortic Aneurysm
Authors: Posso Margarita , Quintana M. Jesús , Bellmunt Sergi , Martínez García Laura , Escudero José R. , Viteri-García Andrés , Valli Claudia , Bonfill Xavier
Published: April 2019

The objective of this study was to provide evidence-based recommendations for endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) for patients with a nonruptured abdominal aortic aneurysm (AAA). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement and adhered to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Both low- and high surgical risk patients treated with EVAR showed decreased 30-day mortality, but the low-risk group had no differences in 4-year mortality. Compared with friendly anatomy, patients with hostile anatomy had an increased risk of type I endoleak. Young patients may prefer OSR. Endovascular aneurysm repair was not cost-effective in Europe. Four conditional recommendations were formulated: (1) OSR for low-risk patients up to 80 years old, (2) EVAR for low-risk patients older than 80 years, (3) EVAR for high-risk patients as long as is anatomically feasible, and (4) OSR in patients in whom it is not anatomically feasible to perform EVAR. Based on GRADE criteria, either OSR or EVAR can be suggested to patients with nonruptured AAA taking into account their surgical risk, hostile anatomy, and age. Given the weakness of the recommendations, personal preferences are determinant.
Differences in Laryngeal Neurotrophic Factor Gene Expression after Recurrent Laryngeal Nerve and Vagus Nerve Injuries
Authors: Halum Stacey L. , Bijangi-Vishehsaraei Khadijeh , Saadatzadeh M. Reza , McRae Bryan R.
Published: April 2019

Objectives

Recurrent laryngeal nerve (RLN) and vagus nerve (VN) injuries characteristically are followed by differing degrees of spontaneous reinnervation, yet laryngeal muscle neurotrophic factor (NF) expression profiles after RLN and VN injuries have not been well elucidated. This study's objective was to determine the relative changes in gene expression of 5 well-characterized NFs from laryngeal muscle after RLN or VN injuries in a time-dependent fashion, and demonstrate how these changes correspond with electromyography-assessed innervation status.

Methods

Thirty-six male rats underwent left RLN transection (12 rats), left VN transection (12 rats), or a sham procedure (12 rats). The primary outcomes included electromyographic assessment and laryngeal muscle NF expression quantification with reverse transcription polymerase chain reaction at 3 days and at 1 month.

Results

Electromyography at 3 days demonstrated electrical silence in the VN injury group, normal activity in the sham group, and nascent units with decreased recruitment in the RLN injury group. Reverse transcription polymerase chain reaction demonstrated that changes in NF gene expression from laryngeal muscles varied depending on the type of nerve injury (RLN or VN) and the specific laryngeal muscle (posterior cricoarytenoid or adductor) assessed.

Conclusions

Laryngeal muscle NF expression profiles after cranial nerve X injury depend both upon the level of nerve injury and upon the muscles involved.
Talk of Calling: Novice School Principals Narrating Destiny, Duty, and Fulfillment in Work
Authors: Swen Carolyn P.
Published: April 2019

Purpose: School principals’ commitment and motivation have not been systematically investigated, but concerted research is needed as 25% of principals leave their jobs each year. This article investigates how new school principals make sense of their motivation to challenging work in a high pressure, high turnover field. Understanding principal motivation is important for recruiting and retaining talented educators. How principals understand their motivation may significantly affect their actions, practices, and persistence. Therefore, insight into principals’ motivation is important. Research Methods: Data come from interviews with 35 new principals in Chicago Public Schools. As initial phases of inductive analyses around principal’s career narratives were completed, this grounded theory inquiry focused on how principals use discourses of calling to make sense of their motivation. Data were analyzed through three iterations of coding: open, focused, and closed. Findings: School principals used themes of calling to make sense of their motivation in challenging contexts. Specifically, they described their destiny to work in education, duty to serve students, and fulfillment in work. Calling narratives explain past action and elevate the importance of the work, likely fueling continued motivation. Implications: This work adds a narrative component to research on principals’ motivation and transition, focusing on principals’ efforts to manage challenges. The results provide novel empirical data on principals’ sense-making, efforts to manage multiplying work demands, and on how professionals use calling to make sense of and bolster work motivation. Future work should determine whether calling narratives predict retention among principals.
An exploration of student, staff, and faculty perceptions on the nature of violence and its prevention at a university in Turkey
Authors: Beaujolais Brieanne , Mengo Cecilia , Karandikar Sharvari
Published: April 2019

The nature of violence within universities in Turkey is an under-researched area. This qualitative study explored the nature of campus violence and its prevention in Turkey. Study results illuminate the nature and forms of violence on campus, and reveal informal and formal structures within the university that address violence prevention. Regarding safety and violence prevention on campus, study participants perceived (a) inadequate university response, (b) lack of policies and procedures, and (c) lack of training about responding to and preventing violence. Perceptions about feeling safe and reporting violence varied based on participant gender. Implications for practice and research are discussed.
Gestational Surrogacy: Current View
Authors: Aznar Justo , Martínez Peris Miriam
Published: April 2019

Surrogate motherhood is an assisted procreation practice by which a woman gestates an embryo with which she has no biological relationship on behalf of a contracting couple or individual, having to relinquish the child to them after its birth. This practice normally entails a financial remuneration for the pregnant woman; when this is not the case, it is called altruistic surrogacy. From a medical perspective, potential problems for the surrogate and for children born through this practice should be taken into account, especially the existence of possible disabilities in the child. The bioethical aspects are of most interest because the practice of surrogacy objectifies the expectant mother, by using her body for a purpose other than her own good, treating her as a commodity, as a thing. The same is true for the child because it makes him a disposable object, something that can be instrumentalized, similarly objectifying him.
Analysis of hygienic face mask patterns for young people
Authors: Morishima Mika , Mitsuno Tamaki
Published: April 2019

The hygienic face mask is a useful textile product for individuals, which covers the wearer’s nose and mouth. One of the hygienic face mask’s performance requirements is a close fit between the mask sheet and the wearer’s facial contours. The present study proposed an optimal shape and size for a mask sheet pattern that provides a sheet with high fit performance for a large number of people. The study experiments analyzed a variety of patterns: i.e. three types of two-dimensional (2D) pattern (i.e. second, third or fourth rings) were used to expand the face mask area to cover the wearers’ nose and mouth (first ring), and were analyzed based on three-dimensional (3D) coordinates of participants’ facial contours ( n = 132) with closed mouths. Subsequently, the analyzed patterns were used to make prototype mask sheets from nonwoven fabric. The fit performances of the face mask sheets were tested using a 3D analyzer. It was difficult to provide high fit performance at all measurement points; therefore, a range of 3 SD in the analyzed pattern was calculated with the aim of fitting more people with 100% precision. The results showed that a number of wearers, i.e. 91.7% (second ring), 93.2% (third ring) and 90.2% (fourth ring), had 100% precision. Moreover, the second ring pattern had the smallest 3 SD amount. These results show that the shape and size of the second ring pattern was most appropriate for young Japanese people with closed mouths.
The U.S. Department of Defense and Its Torture Program
Authors: Arsenault Elizabeth Grimm , Chiang Catherine
Published: April 2019

How did the U.S. Department of Defense (DoD) develop its torture program and, in so doing, stray so significantly from its existing standard operating procedures (SOPs) around humane prisoner treatment? This model of organizational decision-making examines both the ambiguous structural environment that interrogators faced after 9/11 and the ways in which actors used their agency to challenge the procedures and rules that had governed DoD decision-making and actions for more than six decades. By building off the work on organizational theorizing pioneered by Graham Allison and James March, this study process traces the ways in which the DoD’s institutional procedures protecting detainees were developed, challenged, and then ultimately reaffirmed. This research helps organizations ultimately understand the power—and the weaknesses—of their SOPs.
Why are UK junior doctors taking time out of training and what are their experiences? A qualitative study
Authors: Rizan Chantelle , Montgomery Julia , Ramage Charlotte , Welch Jan , Dewhurst Graeme
Published: April 2019

Objectives

The number of doctors directly entering UK specialty training after their foundation year 2 (F2) has steadily declined from 83% in 2010 to 42.6% in 2017. The year following F2, outside the UK training pathway, is informally termed an ‘F3’ year. There is a paucity of qualitative research exploring why increasingly doctors are taking F3s. The aim of this study is to explore the reasons why F2 doctors are choosing to take a year out of training and the impact upon future career choices.

Design

This is an exploratory qualitative study, using in-depth interviews and content analysis.

Setting

UK.

Participants

Fourteen participants were interviewed from one foundation school. Participants included five doctors who commenced their F3 in 2015, five who started in 2016 and finally four recently starting this in 2017.

Main outcome measures

Content analysis was conducted to distill the themes which exemplified the totality of the experience of the three groups.

Results

There were four predominant themes arising within the data set which can be framed as ‘unmet needs’ arising within foundation years, sought to be fulfilled by the F3 year. First, doctors describe exhaustion and stress resulting in a need for a ‘break’. Second, doctors required more time to make decisions surrounding specialty applications and prepare competitive portfolios. Third, participants felt a loss of control which was (partially) regained during their F3s. The final theme was the impact of taking time out upon return to training (for those participants who had completed their F3 year). When doctors returned to NHS posts they brought valuable experience.

Conclusions

This study provides evidence to support the important ongoing initiatives from Health Education England and other postgraduate bodies, exploring approaches to further engage, retain and support the junior doctor workforce.
Overheating risk in Passivhaus dwellings
Authors: Mitchell Rachel , Natarajan Sukumar
Published: April 2019

Highly insulated and airtight homes designed to reduce energy consumption are perceived as having a greater summer overheating risk than less insulated homes. If true, dwellings built to the well-known low-energy Passivhaus (PH) standard could be at greatest risk due to the use of superinsulation, especially as the climate warms. Existing studies are inconclusive and even contradictory, mainly due to small sample sizes. Hence, this paper presents the first large-scale overheating risk analysis of UK Passivhaus dwellings using high-resolution internal temperature data from 82 homes across the UK. Both the Passivhaus and the recently published Chartered Institution of Building Services Engineers TM59 criteria are analysed. Results show that the whole-dwelling Passivhaus standard, which uses a fixed temperature threshold, is met more frequently (83%) than when applied on a room-by-room basis (e.g. only 60% of bedrooms in houses meet the standard). TM59-1A, which uses an adaptive temperature threshold, is easier to meet with 100% of flats and 82% of houses in compliance. However, 55% of bedrooms assessed under TM59-1B fail, with little difference between flats and houses. This is a remarkable finding given that the summers under consideration were either typically mild or cooler than average, and that sleep impairment can significantly affect both physical and mental health. These results suggest that highly insulated dwellings such as Passivhaus should consider overheating in individual rooms, rather than at whole-dwelling level. Analysis should be undertaken throughout the year with particular attention to bedrooms, using either the good-practice PH-5% exceedance threshold which maps well to TM59-1B, or TM59-1B itself.

Practical application: Overheating risk in new dwellings is an industry concern. Having the correct tools to predict this risk at design stage is important to help design comfortable and healthy dwellings for both today's climate and future, hotter climates. Comparing two different tools and their methodologies using in-use data is critical to gain confidence in their application at the design stage and to further understand overheating risk, including which dwelling types and rooms are more vulnerable to overheating.
Governance, CO2 emissions and inclusive human development in sub-Saharan Africa
Authors: Asongu Simplice A , Odhiambo Nicholas M
Published: April 2019

This study investigates the relevance of government quality in moderating the incidence of environmental degradation on inclusive human development in 44 sub-Saharan African countries for the period 2000–2012. Environmental degradation is measured with CO2 emissions and the governance dynamics include: political stability, voice and accountability, government effectiveness, regulation quality, the rule of law and corruption-control. The empirical evidence is based on the generalised method of moments. Regulation quality modulates CO2 emissions to exert a net negative effect on inclusive development. Institutional governance (consisting of corruption-control and the rule of law) modulates CO2 emissions to also exert a net negative effect on inclusive human development. Fortunately, the corresponding interactive effects are positive, which indicates that good governance needs to be enhanced to achieve positive net effects. A policy threshold of institutional governance at which institutional governance completely dampens the unfavourable effect of CO2 emissions on inclusive human development is established. Other policy implications are discussed.
Ameloblastoma of the Sinonasal Tract: A Case Report
Authors: Leong Samuel C. , Karkos Petros D. , Krajacevic Jasna , Islam Rafizul , Kent Stephen E.
Published: April 2019

Ameloblastomas are locally aggressive gnathic tumors with a high propensity for recurrence. Presentation of an ameloblastoma exclusively in the sinonasal tract is extremely rare, with few reported cases in the literature. Management involves surgical excision and close follow-up. We report a case in which the patient had complete unilateral nasal obstruction caused by an ameloblastoma. The tumor was completely excised endoscopically, and at the 12-month follow-up, there was no evidence of recurrence.
Environmental and Ethical Aspects of International Migration
Authors: Abernethy Virginia
Published: April 2019

U.S. immigration policy has a beneficent intent. However, recent work suggests that the signal it sends internationally – that emigration can be relied upon to relieve local (Third World) population pressure – tends to maintain high fertility rates in the sending country. This effect is counterproductive because high fertility is the primary driver of rapid population growth. In addition, it appears that the relatively open U.S. immigration policy has resulted in a rate of domestic population growth that threatens both the well-being of American labor and cherished environmental values.
Co-Occurring Words and Retrieval Efficiency: Finding Information about Alternatives to Animal Testing in Relation to Skin Irritation Testing
Authors: Huggins Jane
Published: April 2019

Words appearing in abstracts of scientific articles are often useful as search terms, particularly those words and word patterns that are unique to the relevant field of endeavour. In view of the heightened interest in obtaining information about alternatives to animal testing, efforts directed toward enhancing retrieval of pertinent references from the bio-medical literature are warranted. Words and phrases, and word–phrase co-occurrences describing methods of experimentation in abstracts about alternatives to skin-irritation testing in animals, were evaluated with regard to retrieval efficiency in the National Library of Medicine database, Toxline™. Precision of retrieval was defined as the number of pertinent references found in the total number of citations retrieved. Retrieval precision values ranged from 0.25% to 100%.
Comparative Evaluation of Five In Vitro Tests for Assessing the Eye Irritation Potential of Hair-care Products
Authors: Jones Penny A. , Budynsky Ella , Cooper Karen J. , Decker Denise , Griffiths Heather A. , Fentem Julia H.
Published: April 2019

This study compared five methods, the isolated rabbit eye (IRE), bovine corneal opacity and permeability (BCOP), EpiOcular™, fluorescein leakage (FL) and neutral red release (NRR) assays, for predicting the eye irritation potential of hair-care formulations. Ten shampoo and seven conditioner formulations of known ocular irritation potential were tested. Each group included a market-acceptable formulation as a comparative benchmark. Predictions of ocular irritation were made by using classification models (IRE, BCOP and EpiOcular assays) or by direct comparison with benchmarks (IRE, EpiOcular, FL and NRR assays). The BCOP assay was less sensitive than the IRE test in discriminating between formulations of different irritation potentials, and did not perform as well as the other assays in identifying mild formulations. All of the assays appeared to be better at discriminating correctly between the shampoos than between the conditioners. The EpiOcular assay showed the closest concordance between the in vivo results and the in vitro data from cell-based assays (particularly for shampoos). The FL assay also showed a high concordance (particularly for conditioners). There was a tendency for these in vitro assays to over-predict eye irritation potential, but there was no under-prediction and they were particularly successful at identifying mild formulations. The NRR assay was less predictive with both shampoos and conditioners. The results from this comparative evaluation fully support the continued use of the IRE test as a suitable alternative to in vivo eye irritation testing in rabbits, although it also over-predicted the irritancies of several of the formulations. The value of using concurrent benchmarks (reference standards), appropriate to the materials being tested, in interpreting the data obtained from in vitro tests, was also demonstrated. Overall, the results indicate that further comparisons of the IRE, EpiOcular and FL assays are warranted using much larger numbers of test materials.
In Vitro Tests for Haematotoxicity: Prediction of Drug-induced Myelosuppression by the CFU-GM Assay
Authors: Pessina Augusto , Albella Beatriz , Bayo Maria , Bueren Juan , Brantom Paul , Casati Silvia , Croera Cristina , Parchment Ralph , Parent-Massin Dominique , Schoeters Greet , Sibiri Yann , Van Den Heuvel Rosette , Gribaldo Laura
Published: April 2019

In a prevalidation study, a Standard Operating Procedure (SOP) for human and mouse in vitro tests was developed, for evaluating the potential haematotoxicity of xenobiotics in terms of their direct, adverse effects on the myeloid colony-forming unit (CFU-GM). Based on the adjustment of the mouse-derived maximum tolerated dose (MTD), a prediction model was set up to calculate the human MTD, and an international blind trial was designed to apply this model to the clinical neutropenia of 23 drugs including 17 antineoplastics. The model correctly predicted the human MTD for 20 drugs out of the 23 (87%). This high percentage of predictivity, and the reproducibility of the SOP testing, confirmed the scientific validation of this model, and suggested promising applications for developing and validating other in vitro methods for use in haematotoxicology.
Selected Biostatistical Aspects of the Validation of In Vitro Toxicological Assays
Authors: Hothorn Ludwig A.
Published: April 2019

An overview is presented on selected biostatistical aspects of the validation of in vitro toxicological assays. Primarily, the statistical analysis of single assays is discussed. Several approaches are compared for the possible non-monotonic dose–response relationship with a priori unknown shapes. The use of confidence intervals instead of p values for toxicologically appropriate decision making is explained. New methods for demonstrating interlaboratory similarity for dose–response designs are discussed. For validation, the inappropriateness of the concordance coefficient is shown, and sensitivity and specificity, as well as predictive values, are proposed as alternatives. The problem of the missing gold standard is highlighted.
The ECVAM Workshops: A Critical Assessment of their Impact on the Development, Validation and Acceptance of Alternative Methods
Authors: Combes Robert D.
Published: April 2019

ECVAM initiated its workshop programme in 1994, to enable it to become well informed about the state of the art of non-animal test development and validation, and about the possible incorporation of alternatives into regulatory requirements for safety testing. Fifty-one such workshops had been held on specific topics, up to 2002. In these workshops, the current status of in vitro tests and their potential uses were reviewed and recommendations were made as to the best ways forward to progress and enhance the use of in vitro methods. Reports for 46 of these workshops have been published in ATLA. Most of the workshops focused on in vitro replacement methods, although an increasing number have dealt with reduction and refinement. The recommendations in the ECVAM workshops have been progressed further by: a) the formation of ECVAM task forces; b) the organisation of further workshops; c) the activities of scientific committees; d) the provision of earmarked research funding; and e) the conduct of validation studies. Examples of each of these activities are discussed. Some individual workshops are covered in more detail, and several recommendations that have so far not been acted on are also considered. The workshops and their reports have had a substantial effect on the development and implementation of alternative methods, and have been a major factor in contributing to the success of the first nine years of ECVAM's existence. It is strongly recommended that ECVAM continues to organise workshops and to publish their findings, and suggestions are made for topics for future workshops.
ECVAM's Collaboration with Academia
Authors: Clothier Richard
Published: April 2019

The encouragement of ECVAM's connections with academia through direct collaboration and co-sponsored studentships has resulted in the successful achievement of higher degree qualifications for the young participants, and the development and promotion of alternative methods. So far, 26 students have been registered for higher degrees, 13 of which have been awarded so far, and 16 university departments in nine European countries have been directly involved. When other collaborations are included, the number of ECVAM's interactions with academic institutions rises to 33 departments in eleven countries, including the USA. In addition, through contracts awarded to academic institutions and other forms of collaboration, the prevalidation and validation of alternative methods have been progressed.
Comments on the Sixth Report of the Animal Welfare Advisory Committee
Authors: Vaughan Sylvia
Published: April 2019

The Animal Welfare Advisory Committee (AWAC) was established in July 1996, to consider the care, welfare and use of animals involved in procedures for defence research purposes at Defence and Evaluation Research Agency (DERA) establishments in the UK. Two of the objectives of AWAC are to examine the broad trends in animal use at DERA establishments, and to implement and audit the application of the Three Rs principle. AWAC's sixth report addressed the period from 31 October 2000 to 28 February 2002. The statistics of animal use within the report are briefly examined, and some of the actions undertaken by defence research establishments to facilitate the application of the Three Rs are highlighted. It is recommended that, if possible (subject to security constraints), figures detailing the severity of the procedures undertaken should be included in future issues of the report, in order to provide a more-detailed account. It is concluded that Defence Science and Technology Laboratory establishments have made a contribution to the Three Rs, and that other establishments may be able to incorporate some of their actions into their own research programmes. There was an overall 36% increase in the number of procedures carried out by defence research establishments between 1995 and 2000, from 8,900 to 12,065. This probably reflects alterations in the research programme, which is, in turn, decided primarily by the Ministry of Defence's customers and the progress made with previous research programmes. It is therefore recommended that the UK Government allocates significantly more financial resources for the development and validation of alternatives, in order to maximise the potential for achieving the Three Rs in defence research, and to complement the existing initiatives within the defence research industry.
Statistical Analysis of Monotone or Non-monotone Dose–Response Data from In Vitro Toxicological Assays
Authors: Bretz Frank , Hothorn Ludwig A.
Published: April 2019

Various tests on trend in toxicological studies are reviewed, and the advantages and the disadvantages involved with such procedures are discussed. New tests are introduced to overcome difficulties common to many current procedures, such as downturns at higher doses, and missing numerical availability.
Validation of the Postimplantation Rat Whole-embryo Culture Test in the International ECVAM Validation Study on Three In Vitro Embryotoxicity Tests
Authors: Piersma Aldert H. , Genschow Elke , Verhoef Aart , Spanjersberg Marielle Q.I. , Brown Nigel A. , Brady Madeleine , Burns Angie , Clemann Nicole , Seiler Andrea , Spielmann Horst
Published: April 2019

A detailed report is presented on the performance of the postimplantation rat whole-embryo culture (WEC) test in a European Centre for the Validation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects in animals and/or humans, were tested in four laboratories. The outcome showed that the WEC test can be considered to be a scientifically validated test, which is ready for consideration for use in assessing the embryotoxic potentials of chemicals for regulatory purposes.
Characterisation of Human Corneal Epithelial Cell Cultures Maintained under Serum-free Conditions
Authors: Seeber Judith W. , Zorn-Kruppa Michaela , Lombardi-Borgia Simone , Scholz Heike , Manzer Anna K. , Rusche Brigitte , Schäfer-Korting Monika , Engelke Maria
Published: April 2019

Three-dimensional tissue constructs have been proposed as in vitro screening models for ocular irritancy. Based on our previous studies, in which a full-thickness corneal model based exclusively on SV40-immortalised cell lines was generated, we have currently evaluated the effects of a range of commercially-available cell culture media on several cellular parameters in cultures of a human corneal epithelial (HCE) cell line. This cell line was used in an attempt to establish a rational basis for the development of serum-free culture media for the assembly and long-term tissue culture of full-thickness corneal models. Briefly, we investigated the impact of serum-free culture on the proliferation, morphology, barrier function and cytokine expression of HCE cells. The number of cell layers and the epithelial differentiation were evaluated by histology. Barrier properties were characterised via the determination of transepithelial electrical resistance (TEER), fluorescein permeation, and the expression of the tight junction-related protein, zona occludin 1 (ZO-1). The cytokine expression pattern in response to serum-free culture was measured by using an antibody array system. Our results revealed that both the morphology and the barrier function of the epithelial constructs were comparable to those of human donor corneas, when serum-free media were supplemented with ascorbic acid, calcium, hydrocortisone and retinoic acid. Under these conditions, the artificial epithelium based on serum-free HCE cultures represented a valid model for the natural ocular surface.
An In Vitro Tier Evaluation for the Identification of Cosmetic Ingredients Which are Not Ocular Irritants
Authors: Hagino Shigenobu , Okazaki Yuuko , Itagaki Hiroshi
Published: April 2019

A tier evaluation system was assessed as an alternative method for the identification of cosmetic ingredients which are not ocular irritants. The system employed monolayer cultures of SIRC cells, an established cell line originally derived from the rabbit cornea, and a three-dimensional living dermal model (LDM), MATREX™, which consists of human dermal fibroblasts in a contracted collagen lattice. Effects on the cell monolayer cultures were determined by using SIRC cell-Crystal Violet staining (SIRC-CVS), and effects on the LDM were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A non-irritating ingredient was defined as a compound having a maximal average total score (MAS) of 5 or less in the Draize eye test, as this is the criterion used in the Japanese draft guidance for evaluating cosmetic ingredients. Among 34 test substances with known characteristics, 30 were classified accurately. Based on these encouraging results, the possibility of simplifying the MTT assay on the LDM for more-practical use, by selecting only three concentration levels to discriminate non-irritants from irritants, was assessed. The simplified method, involving a three-dose set (the three-dose method), was confirmed as being suitable for the identification of non-irritating ingredients, with triethanolamine used as a negative reference standard. Finally, the LDM was used to evaluate compounds at similar concentrations to those tested in vivo, aiming to predict the concentration at which an ingredient can be formulated into products without causing eye irritation. On the basis of previous validation data and our additional results, it was found that test samples that resulted in a cell viability of 50% or more in this model, could be classified as non-irritating ingredients. In all, these results indicate that the tier evaluation system may be suitable for the evaluation of ingredients intended to be used in cosmetics and medicated cosmetics in Japan.
Systems Biology in Alternatives: The Importance of Human-based Studies
Authors: Bennett Andrew
Published: April 2019

The aim of research in the FRAME Alternatives Laboratory at the University of Nottingham Medical School is summarised, i.e. to use human cell culture-based projects and in vivo studies in human volunteers as alternatives to the use of rodent models in the study of human disease. This is especially important when the available animal models do not adequately represent the pathophysiological situation in humans. The approach is exemplified by summaries of studies on the effects of starvation on skeletal muscle in human volunteers, and on lipid metabolism in obese female volunteers.
Per Aspirin ad Astra…
Authors: Hartung Thomas
Published: April 2019

Taking the 110th anniversary of marketing of aspirin as starting point, the almost scary toxicological profile of aspirin is contrasted with its actual use experience. The author concludes that we are lucky that, in 1899, there was no regulatory toxicology. Adding, for the purpose of this article, a fourth R to the Three Rs, i.e. Realism, three reality-checks are carried out. The first one comes to the conclusion that the tools of toxicology are hardly adequate for the challenges ahead. The second one concludes that, specifically, the implementation of the EU REACH system is not feasible with these tools, mainly with regard to throughput. The third one challenges the belief that classical alternative methods, i.e. replacing animal test-based tools one by one, is actually leading to a new toxicology — it appears to change only patches of the patchwork, but not to overcome any inherent limitations other than ethical ones. The perspective lies in the Toxicology for the 21st Century initiatives, which aim to create a new approach from the scratch, by an evidence-based toxicology and a global “Human Toxicology Programme”.
The Development and Evaluation of In Vitro Alternative Assays: A Personal Perspective
Authors: Clothier Richard
Published: April 2019

Over the past 30 years, FRAME has actively participated in the development, evaluation and validation of in vitro alternative methods through the FRAME Alternatives Laboratory (FAL) in the University of Nottingham Medical School. Much has been learned through collaboration with industry (especially the cosmetics industry), other organisations (especially ECVAM), and certain individuals (notably Dr Björn Ekwall), particularly in relation to the need to use human cell cultures and to obtain, wherever possible, high-quality human data for use in in vivo/in vitro comparisons. Reference is made to the author's experience as Director of the FAL, notably in the development of in vitro assays for basal cytotoxicity, phototoxicity and the effects of repeated dosage.
The Value of In Vitro Models of the Blood–Brain Barrier and Their Uses
Authors: Patabendige Adjanie
Published: April 2019

A range of in vitro BBB models are available, that can simplify the complexities associated with the in vivo study of the BBB. However, the adoption of these models, especially for studying the pathology of the BBB, is still poor, despite their ability to complement and reduce animal experiments
We are not Born Knowing how to Design and Analyse Scientific Experiments
Authors: Festing Michael F.W.
Published: April 2019

Better training in experimental techniques and changes to the current methods of scientific research funding are both needed to facilitate more-effective improvements in human health
Refinement
Authors: Howard Bryan
Published: April 2019

Russell and Burch's principle of refinement has endured from its inception in the 1950s, to appear in today's EU Directive
Current Status of Animal Welfare and Animal Rights in China
Authors: Lu Jiaqi , Bayne Kathryn , Wang Jianfei
Published: April 2019

In the past few years, new social passions have sparked on the Chinese mainland. At the centre of these burgeoning passions is a focus on animal welfare, animal treatment, and even animal rights, by the public and academic sectors. With China's rapid economic changes and greater access to information from around the world, societal awareness of animal issues is rising very fast. Hastening this paradigm shift were several highly public incidents involving animal cruelty, including exposés on bear bile harvesting for traditional Chinese medicine, the thousands of dogs rescued from China's meat trade, and the call to boycott shark fin soup and bird nest soup. This article outlines the current status of campaigning by animal advocates in China (specifically the animal rights movement) from three interlinked perspectives: wildlife conservation, companion animal protection, and laboratory animal protection. By reviewing this campaigning, we attempt to present not only the political and social impact of the concept of animal rights, but also the perceptions of, and challenges to, animal rights activities in China.
Turning Apples into Oranges? The Harm-Benefit Analysis and how to Take Ethical Considerations into Account
Authors: Grimm Herwig
Published: April 2019

How can expected study benefits and animal harms be weighed against each other? What is the unit and common currency that allows this weighing to be performed?
The 2016 Lush Prize Awards
Authors: BéruBé Kelly , Redmond Craig
Published: April 2019

This year saw the launch of additional categories to reward young scientists in both Asia and the Americas
Animal Research for Type 2 Diabetes Mellitus, Its Limited Translation for Clinical Benefit, and the Way Forward
Authors: Ali Zeeshan , Chandrasekera P. Charukeshi , Pippin John J.
Published: April 2019

Obesity and type 2 diabetes mellitus (T2DM) have reached pandemic proportions worldwide, and considerable research efforts have been dedicated to investigating disease pathology and therapeutic options. The two hallmark features of T2DM, insulin resistance and pancreatic dysfunction, have been studied extensively by using various animal models. Despite the knowledge acquired from such models, particularly mechanistic discoveries that sometimes mimic human T2DM mechanisms or pathways, many details of human T2DM pathogenesis remain unknown, therapeutic options remain limited, and a cure has eluded research. Emerging human data have raised concern regarding inter-species differences at many levels (e.g. in gene regulation, pancreatic cytoarchitecture, glucose transport, and insulin secretion regulation), and the subsequent impact of these differences on the clinical translation of animal research findings. Therefore, it is important to recognise and address the translational gap between basic animal-based research and the clinical advances needed to prevent and treat T2DM. The purpose of this report is to identify some limitations of T2DM animal research, and to propose how greater human relevance and applicability of hypothesis-driven basic T2DM research could be achieved through the use of human-based data acquisition at various biological levels. This report addresses how in vitro, in vivo and in silico technologies could be used to investigate particular aspects of human glucose regulation. We do not propose that T2DM animal research has been without value in the identification of mechanisms, pathways, or potential targets for therapies, nor do we claim that human-based methods can provide all the answers. We recognise that the ultimate goal of T2DM animal research is to identify ways to advance the prevention, recognition and treatment of T2DM in humans, but postulate that this is where the use of animal models falls short, despite decades of effort. The best way to achieve this goal is by prioritising human-centred research.
The Development of a Clinical Skills Laboratory at Ross University School of Veterinary Medicine
Authors: Grevemeyer Bernard , Knight Andrew
Published: April 2019

Dedicated clinical skills laboratories (CSLs) that make use of models, mannequins and simulators, are being increasingly established in medical and veterinary schools. These have been commonplace in medical schools for more than two decades, but their incorporation within the teaching of veterinary curricula has occurred much more recently. In 2007, a decision was taken to establish a CSL at Ross University School of Veterinary Medicine. We considered the range of skills that we wished to teach, the physical space and equipment needed, the storage and air conditioning requirements, the facilities needed to deliver PowerPoint lectures and case study presentations, and other essentials necessary to handle cadaver specimens. We converted an appropriate campus building to our needs, hired teaching staff, and started to source models and mannequins for the teaching of veterinary clinical skills. In 2010, 177 senior students completed a survey evaluating their experiences within our CSL. Student satisfaction was generally high, with 95% of respondents feeling that the CSL had improved their psychomotor skills. However, 15% of them felt that the models were insufficiently realistic. Our clinical skills programme has since developed considerably, and it currently offers instruction in a diverse array of surgical, medical and other clinical skills. We hope that this description of our experiences may assist others embarking on similar projects elsewhere.
A Comparison of Pyrogen Detection Tests in the Quality Control of Meningococcal Conjugate Vaccines: The Applicability of the Monocyte Activation Test
Authors: Silva Vitor Fernandes , da Silva Guedes Junior Daniel , da Silveira Ivna Alana , Almeida Alessandra Santos , de Paiva Conte Fernando , Delgado Isabella Fernandes , Silva Cristiane Caldeira , Presgrave Octavio Augusto França , de Mattos Katherine Antunes
Published: April 2019

The meningococcal C conjugate vaccine (MenCC) is an interesting model with which to test the efficacy of the Monocyte Activation Test (MAT) as an alternative method of pyrogen testing in the quality control of vaccines. The MenCC that has been produced by Bio-Manguinhos in Brazil is in the final development stage, and, as recommended in the guidelines for MenCC production, its pyrogen content must be determined by using the Limulus Amoebocyte Lysate (LAL) assay and the Rabbit Pyrogen Test (RPT). This represents an ideal opportunity to compare LAL and RPT data with data obtained by using a MAT system with cryopreserved whole blood and IL-6/IL-1β as marker readouts. In order to assess the compatibility of the MAT with MenCC, endotoxin and non-endotoxin pyrogen content was quantified by using MenCC samples spiked with lipopolysaccharide (LPS), lipoteichoic acid or zymosan standards. The presence of the aluminium-based adjuvant interfered with the MAT, increasing the readout of IL-1β in LPS-spiked MenCC batches. This infringed the product-specific validation criteria of the test, and led to IL-6 being chosen as the more suitable marker readout. No pyrogenic contaminants were identified in the MenCC batches tested, demonstrating consistency among the different systems (MAT, RPT and the LAL assay). In conclusion, the introduction of the MAT during MenCC development could contribute to the elimination of animal tests post-licensing, ensuring human protection based on an effective non-animal based method of quality control.
Where to Draw the Line? Should the Age of Protection for Zebrafish be Lowered?
Authors: Sneddon Lynne U.
Published: April 2019

Zebrafish are not protected by legislation in many countries until they reach the first feed stage, typically at five days post-fertilisation. If they exhibit similar responses to adults when responding to pain and other stimuli should they be given more protection?