Is the Femoral-Epiphyseal Acetabular Roof (FEAR) index associated with hip pain in patients with hip dysplasia?

BACKGROUND: Micro instability of the hip joint has been suggested to cause pain in patients with hip dysplasia. Recently, the Femoral-Epiphyseal Acetabular Roof (FEAR) index has been developed to evaluate hip instability in patients with dysplasia. PURPOSE: To investigate associations between the FEAR index and patient-reported outcomes before and six months after periacetabular osteotomy (PAO). MATERIAL AND METHODS: Radiographs of patients with hip dysplasia who underwent PAO between 2018 and 2020 were retrospectively assessed by a radiologist and an orthopedic surgeon. Radiographic measurements indicative of hip instability (Shenton's line, FEAR index, center-edge angle of Wiberg, acetabular index of Tönnis, and the femoral neck-shaft angle) were measured. Data on hip pain, function, and quality of life were collected prospectively using the Hip dysfunction and Osteoarthritis Outcome Score (HOOS). RESULTS: A total of 222 patients were included in the study. All radiographic measurements and patient-reported outcomes improved significantly from preoperative to six months postoperative (P < 0.001). There were no differences in the change score of patient-reported outcomes between patients with a FEAR index >2° (indicative of hip instability) and patients with a FEAR index ≤2°. CONCLUSION: The FEAR index was not associated with hip pain, function, and quality of life among patients with hip dysplasia. This study did not find evidence supporting that instability defined by the FEAR index caused pain in patients with hip dysplasia.

A Model for Cognitive Personalization of Microtask Design.

The study of data quality in crowdsourcing campaigns is currently a prominent research topic, given the diverse range of participants involved. A potential solution to enhancing data quality processes in crowdsourcing is cognitive personalization, which involves appropriately adapting or assigning tasks based on a crowd worker's cognitive profile. There are two common methods for assessing a crowd worker's cognitive profile: administering online cognitive tests, and inferring behavior from task fingerprinting based on user interaction log events. This article presents the findings of a study that investigated the complementarity of both approaches in a microtask scenario, focusing on personalizing task design. The study involved 134 unique crowd workers recruited from a crowdsourcing marketplace. The main objective was to examine how the administration of cognitive ability tests can be used to allocate crowd workers to microtasks with varying levels of difficulty, including the development of a deep learning model. Another goal was to investigate if task fingerprinting can be used to allocate crowd workers to different microtasks in a personalized manner. The results indicated that both objectives were accomplished, validating the usage of cognitive tests and task fingerprinting as effective mechanisms for microtask personalization, including the development of a deep learning model with 95% accuracy in predicting the accuracy of the microtasks. While we achieved an accuracy of 95%, it is important to note that the small dataset size may have limited the model's performance.

Trajectory for 66 patients treated with periacetabular osteotomy (PAO) and subsequent total hip arthroplasty: a follow-up study including 1378 hips from the Aarhus PAO database.

INTRODUCTION: Outcomes for patients treated with PAO and subsequent total hip arthroplasty (THA) remain unclear. We evaluated patient-reported outcomes among patients treated with PAO and subsequent THA and investigated differences in the number of additional surgical procedures after PAO among patients treated with PAO and subsequent THA and patients treated with PAO only. MATERIALS AND METHODS: 1378 hips underwent PAO and subsequently 66 hips were treated with THA. We evaluated the Hip disability and Osteoarthritis Outcome Score (HOOS) and physical activity questions for the 66 hips. Additional surgery after PAO was identified through inquiry to the Danish National Patient Registry. RESULTS: 13% undergoing PAO and subsequent THA reported a HOOS pain score ≤ 50 indicating a clinical failure. The risk difference for hip arthroscopy after PAO within 2 and 4 years was 14% (CI 5-23%) and 26% (CI 15-38%) in favor of hips treated with PAO only. Similarly, the risk difference for screw removal within 2 and 4 years was 19% (CI 8-29%) and 23% (CI 12-34%). CONCLUSION: 87% of patients undergoing PAO and subsequent THA had little or no hip pain. However, these patients received a high number of additional surgeries after PAO. Surgeons and patients may consider if additional surgery after PAO may be the first choice in a series of actions leading to conversion to THA.

Laparoscopy assisted abomasal cannulation in cadavers of bovine fetuses.

BACKGROUND: Due to the complexity of ruminant digestion, cannulation of organs of the digestive tract has been carried out in order to advance the understanding of digestive physiology, nutrient degradability, gastrointestinal diseases and biotechnological research. The abomasal cannulation is interesting for nutritional studies, especially in suckling calves, to obtain fluid and abomasal content, evaluation of abomasal flow and function, and infusion of nutrients and drugs when it is intended to reach high concentrations in the organ. Conventionally, access and cannulation of digestive organs of ruminants has been performed by laparotomy, a method often criticized and classified as cruel by some sectors related to ethics and animal welfare. The aim of this present study is to describe and standardize a minimally invasive by laparoscopy assisted abomasal cannulation in bovine fetuses (cadavers), which had been previously slaughtered by accident and would be discarded in local slaughterhouses. RESULTS: The abomasal cannulation technique was feasible, simple and did not present major difficulties. The surgical time for cannulation of the abomasum, from the insertion of the trocars to the completion of the technique with fixation of the organ to the abdominal wall, ranged from 9 to 27 min, with an average of 15.5 ± 6.62 min. CONCLUSIONS: The Laproscopic assisted abomasal cannulation in bovine fetuses was feasible and safe with minimal tissue injury to the abdominal wall and with short surgical time. More studies in the clinical routine related to minimally invasive abomasal content collection, abomasopexy and abomasotomy are required in order to demonstrate its impact and importance in bovine clinic.

Percutaneous ruminostomy guided by rumenoscopy: study in an experimental model in bovine fetus.

BACKGROUND: Endosurgery is a surgical subspecialty that has been widely used in production animals, because it enables good visualization of abdominal organs and the diagnosis and treatment of several conditions in a minimally invasive manner, while preserving the animal's well-being and causing a lower impact on animal production. Rumenostomy is one of the most common surgical procedures in ruminants. This procedure is used to allow access to the rumen for various purposes, especially nutritional and therapeutic studies, and it can be performed either in a conventional way or in a minimally invasive video-assisted manner. Another possibility of access to ruminants is through the rumenoscopy technique. The objective of this study is to describe a minimally invasive technique for rumenostomy using an endoscope, working on a bovine fetal corpse as an experimental model. RESULTS: The execution of the endoscopy-guided rumenostomy technique was simple and did not present major difficulties. The endoscope, its lighting and air pump, and the decubitus used provided a good anatomical visualization of the rumen, and it was possible to evaluate several regions of the organ. The mean duration of the procedure was 11.15 min. CONCLUSIONS: The endoscopic rumenostomy technique using anatomical pieces of calves was shown to be feasible. It was performed in a simple and efficient way, particularly regarding the premise of preserving the animal's well-being, due to its minimally invasive nature.

A framework for establishing scientific confidence in new approach methodologies.

Robust and efficient processes are needed to establish scientific confidence in new approach methodologies (NAMs) if they are to be considered for regulatory applications. NAMs need to be fit for purpose, reliable and, for the assessment of human health effects, provide information relevant to human biology. They must also be independently reviewed and transparently communicated. Ideally, NAM developers should communicate with stakeholders such as regulators and industry to identify the question(s), and specified purpose that the NAM is intended to address, and the context in which it will be used. Assessment of the biological relevance of the NAM should focus on its alignment with human biology, mechanistic understanding, and ability to provide information that leads to health protective decisions, rather than solely comparing NAM-based chemical testing results with those from traditional animal test methods. However, when NAM results are compared to historical animal test results, the variability observed within animal test method results should be used to inform performance benchmarks. Building on previous efforts, this paper proposes a framework comprising five essential elements to establish scientific confidence in NAMs for regulatory use: fitness for purpose, human biological relevance, technical characterization, data integrity and transparency, and independent review. Universal uptake of this framework would facilitate the timely development and use of NAMs by the international community. While this paper focuses on NAMs for assessing human health effects of pesticides and industrial chemicals, many of the suggested elements are expected to apply to other types of chemicals and to ecotoxicological effect assessments.

SAR.IoT: Secured Augmented Reality for IoT Devices Management.

Currently, solutions based on the Internet of Things (IoT) concept are increasingly being adopted in several fields, namely, industry, agriculture, and home automation. The costs associated with this type of equipment is reasonably small, as IoT devices usually do not have output peripherals to display information about their status (e.g., a screen or a printer), although they may have informative LEDs, which is sometimes insufficient. For most IoT devices, the price of a minimalist display, to output and display the device's running status (i.e., what the device is doing), might cost much more than the actual IoT device. Occasionally, it might become necessary to visualize the IoT device output, making it necessary to find solutions to show the hardware output information in real time, without requiring extra equipment, only what the administrator usually has with them. In order to solve the above, a technological solution that allows for the visualization of IoT device information in actual time, using augmented reality and a simple smartphone, was developed and analyzed. In addition, the system created integrates a security layer, at the level of AR, to secure the shown data from unwanted eyes. The results of the tests carried out allowed us to validate the operation of the solution when accessing the information of the IoT devices, verify the operation of the security layer in AR, analyze the interaction between smartphones, the platform, and the devices, and check which AR markers are most optimized for this use case. This work results in a secure augmented reality solution, which can be used with a simple smartphone, to monitor/manage IoT devices in industrial, laboratory or research environments.

Distributed Architecture for Unmanned Vehicle Services.

The demand for online services is increasing. Services that would require a long time to understand, use and master are becoming as transparent as possible to the users, that tend to focus only on the final goals. Combined with the advantages of the unmanned vehicles (UV), from the unmanned factor to the reduced size and costs, we found an opportunity to bring to users a wide variety of services supported by UV, through the Internet of Unmanned Vehicles (IoUV). Current solutions were analyzed and we discussed scalability and genericity as the principal concerns. Then, we proposed a solution that combines several services and UVs, available from anywhere at any time, from a cloud platform. The solution considers a cloud distributed architecture, composed by users, services, vehicles and a platform, interconnected through the Internet. Each vehicle provides to the platform an abstract and generic interface for the essential commands. Therefore, this modular design makes easier the creation of new services and the reuse of the different vehicles. To confirm the feasibility of the solution we implemented a prototype considering a cloud-hosted platform and the integration of custom-built small-sized cars, a custom-built quadcopter, and a commercial Vertical Take-Off and Landing (VTOL) aircraft. To validate the prototype and the vehicles' remote control, we created several services accessible via a web browser and controlled through a computer keyboard. We tested the solution in a local network, remote networks and mobile networks (i.e., 3G and Long-Term Evolution (LTE)) and proved the benefits of decentralizing the communications into multiple point-to-point links for the remote control. Consequently, the solution can provide scalable UV-based services, with low technical effort, for anyone at anytime and anywhere.

IndoorCare: Low-Cost Elderly Activity Monitoring System through Image Processing.

The Portuguese population is aging at an increasing rate, which introduces new problems, particularly in rural areas, where the population is small and widely spread throughout the territory. These people, mostly elderly, have low income and are often isolated and socially excluded. This work researches and proposes an affordable Ambient Assisted Living (AAL)-based solution to monitor the activities of elderly individuals, inside their homes, in a pervasive and non-intrusive way, while preserving their privacy. The solution uses a set of low-cost IoT sensor devices, computer vision algorithms and reasoning rules, to acquire data and recognize the activities performed by a subject inside a home. A conceptual architecture and a functional prototype were developed, the prototype being successfully tested in an environment similar to a real case scenario. The system and the underlying concept can be used as a building block for remote and distributed elderly care services, in which the elderly live autonomously in their homes, but have the attention of a caregiver when needed.

Web AR Solution for UAV Pilot Training and Usability Testing.

Data and services are available anywhere at any time thanks to the Internet and mobile devices. Nowadays, there are new ways of representing data through trendy technologies such as augmented reality (AR), which extends our perception of reality through the addition of a virtual layer on top of real-time images. The great potential of unmanned aerial vehicles (UAVs) for carrying out routine and professional tasks has encouraged their use in the creation of several services, such as package delivery or industrial maintenance. Unfortunately, drone piloting is difficult to learn and requires specific training. Since regular training is performed with virtual simulations, we decided to propose a multiplatform cloud-hosted solution based in Web AR for drone training and usability testing. This solution defines a configurable trajectory through virtual elements represented over barcode markers placed on a real environment. The main goal is to provide an inclusive and accessible training solution which could be used by anyone who wants to learn how to pilot or test research related to UAV control. For this paper, we reviewed drones, AR, and human-drone interaction (HDI) to propose an architecture and implement a prototype, which was built using a Raspberry Pi 3, a camera, and barcode markers. The validation was conducted using several test scenarios. The results show that a real-time AR experience for drone pilot training and usability testing is achievable through web technologies. Some of the advantages of this approach, compared to traditional methods, are its high availability by using the web and other ubiquitous devices; the minimization of technophobia related to crashes; and the development of cost-effective alternatives to train pilots and make the testing phase easier for drone researchers and developers through trendy technologies.

Human-relevant approaches to assess eye corrosion/irritation potential of agrochemical formulations.

There are multiple in vitro and ex vivo eye irritation and corrosion test methods that are available as internationally harmonized test guidelines for regulatory use. Despite their demonstrated usefulness to a broad range of substances through inter-laboratory validation studies, they have not been widely adopted for testing agrochemical formulations due to a lack of concordance with parallel results from the traditional regulatory test method for this endpoint, the rabbit eye test. The inherent variability of the rabbit test, differences in the anatomy of the rabbit and human eyes, and differences in modelling exposures in rabbit eyes relative to human eyes contribute to this lack of concordance. Ultimately, the regulatory purpose for these tests is protection of human health, and, thus, there is a need for a testing approach based on human biology. This paper reviews the available in vivo, in vitro and ex vivo test methods with respect to their relevance to human ocular anatomy, anticipated exposure scenarios, and the mechanisms of eye irritation/corrosion in humans. Each of the in vitro and ex vivo methods described is generally appropriate for identifying non-irritants. To discriminate among eye irritants, the human three-dimensional epithelial and full thickness corneal models provide the most detailed information about the severity of irritation. Consideration of the mechanisms of eye irritation, and the strengths and limitations of the in vivo, in vitro and ex vivo test methods, show that the in vitro/ex vivo methods are as or more reflective of human biology and less variable than the currently used rabbit approach. Suggestions are made for further optimizing the most promising methods to distinguish between severe (corrosive), moderate, mild and non-irritants and provide information about the reversibility of effects. Also considered is the utility of including additional information (e.g. physical chemical properties), consistent with the Organization for Economic Cooperation and Development's guidance document on an integrated approach to testing and assessment of potential eye irritation. Combining structural and functional information about a test substance with test results from human-relevant methods will ensure the best protection of humans following accidental eye exposure to agrochemicals.

UAV Landing Using Computer Vision Techniques for Human Detection.

The capability of drones to perform autonomous missions has led retail companies to use them for deliveries, saving time and human resources. In these services, the delivery depends on the Global Positioning System (GPS) to define an approximate landing point. However, the landscape can interfere with the satellite signal (e.g., tall buildings), reducing the accuracy of this approach. Changes in the environment can also invalidate the security of a previously defined landing site (e.g., irregular terrain, swimming pool). Therefore, the main goal of this work is to improve the process of goods delivery using drones, focusing on the detection of the potential receiver. We developed a solution that has been improved along its iterative assessment composed of five test scenarios. The built prototype complements the GPS through Computer Vision (CV) algorithms, based on Convolutional Neural Networks (CNN), running in a Raspberry Pi 3 with a Pi NoIR Camera (i.e., No InfraRed-without infrared filter). The experiments were performed with the models Single Shot Detector (SSD) MobileNet-V2, and SSDLite-MobileNet-V2. The best results were obtained in the afternoon, with the SSDLite architecture, for distances and heights between 2.5-10 m, with recalls from 59%-76%. The results confirm that a low computing power and cost-effective system can perform aerial human detection, estimating the landing position without an additional visual marker.

Validation of the OptiSafe™ eye irritation test.

PURPOSE: OptiSafe is an in chemico test method that identifies potential eye irritants based on macromolecular damage following test chemical exposure. The OptiSafe protocol includes a prescreen assessment that identifies test chemicals that are outside the applicability domain of the test method and thus determines the optimal procedure. We assessed the usefulness and limitations of the OptiSafe test method for identifying chemicals not requiring classification for ocular irritation (i.e. bottom-up testing strategy). MATERIALS AND METHODS: Seventeen chemicals were selected by the lead laboratory and tested as an independent study. Ninety-five unique coded chemicals were selected by a validation management team to assess the intra- and interlaboratory reproducibility and accuracy of OptiSafe in a multilaboratory, three-phased validation study. Three laboratories (lead laboratory and two naïve laboratories) evaluated 35 chemicals, with the remaining 60 chemicals evaluated by the lead laboratory only. Test method performance was assessed by comparing classifications based on OptiSafe results to classifications based on available retrospective in vivo data, using both the EPA and GHS eye irritation hazard classification systems. No prospective in vivo testing was conducted. RESULTS: Phase I testing of five chemicals showed that the method could be transferred to naïve laboratories; within-lab reproducibility ranged from 93% to 100% for both classification systems. Thirty coded chemicals were evaluated in Phase II of the validation study to demonstrate both intra- and interlaboratory reproducibility. Intralaboratory reproducibility for both EPA and GHS classification systems for Phase II of the validation study ranged from 93% to 99%, while interlaboratory reproducibility was 91% for both systems. Test method accuracy for the EPA and GHS classification systems based on results from individual laboratories ranged from 82% to 88% and from 78% to 88%, respectively, among the three laboratories; false negative rates ranged from 0% to 7% (EPA) and 0% to 15% (GHS). When results across all three laboratories were combined based on the majority classification, test method accuracy and false negative rates were 89% and 0%, respectively, for both classification systems, while false positive rates were 25% and 23% for the EPA and GHS classification systems, respectively. Validation study Phase III evaluation of an additional 60 chemicals by the lead laboratory provided a comprehensive assessment of test method accuracy and defined the applicability domain of the method. Based on chemicals tested in Phases II and III by the lead laboratory, test method accuracy was 83% and 79% for the EPA and GHS classification systems, respectively; false negative rates were 4% (EPA) and 0% (GHS); and false positive rates were 40% (EPA) and 42% (GHS). Potential causes of false positives in certain chemical (e.g. ethers and alcohols) or hazard classes are being further investigated. CONCLUSION: The OptiSafe test method is useful for identifying nonsurfactant substances not requiring classification for ocular irritancy. OptiSafe represents a new tool for the in vitro assessment of ocular toxicity in a tiered-testing strategy where chemicals can be initially tested and identified as not requiring hazard classification.

United States regulatory requirements for skin and eye irritation testing.

PURPOSE: Eye and skin irritation test data are required or considered by chemical regulation authorities in the United States to develop product hazard labelling and/or to assess risks for exposure to skin- and eye-irritating chemicals. The combination of animal welfare concerns and interest in implementing methods with greater human relevance has led to the development of non-animal skin- and eye-irritation test methods. To identify opportunities for regulatory uses of non-animal replacements for skin and eye irritation tests, the needs and uses for these types of test data at U.S. regulatory and research agencies must first be clarified. METHODS: We surveyed regulatory and non-regulatory testing needs of U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) agencies for skin and eye irritation testing data. Information reviewed includes the type of skin and eye irritation data required by each agency and the associated decision context: hazard classification, potency classification, or risk assessment; the preferred tests; and whether alternative or non-animal tests are acceptable. Information on the specific information needed from non-animal test methods also was collected. RESULTS: A common theme across U.S. agencies is the willingness to consider non-animal or alternative test methods. Sponsors are encouraged to consult with the relevant agency in designing their testing program to discuss the use and acceptance of alternative methods for local skin and eye irritation testing. CONCLUSIONS: To advance the implementation of alternative testing methods, a dialog on the confidence of these methods to protect public health and the environment must be undertaken at all levels.

International regulatory requirements for skin sensitization testing.

Skin sensitization test data are required or considered by chemical regulation authorities around the world. These data are used to develop product hazard labeling for the protection of consumers or workers and to assess risks from exposure to skin-sensitizing chemicals. To identify opportunities for regulatory uses of non-animal replacements for skin sensitization tests, the needs and uses for skin sensitization test data must first be clarified. Thus, we reviewed skin sensitization testing requirements for seven countries or regions that are represented in the International Cooperation on Alternative Test Methods (ICATM). We noted the type of skin sensitization data required for each chemical sector and whether these data were used in a hazard classification, potency classification, or risk assessment context; the preferred tests; and whether alternative non-animal tests were acceptable. An understanding of national and regional regulatory requirements for skin sensitization testing will inform the development of ICATM's international strategy for the acceptance and implementation of non-animal alternatives to assess the health hazards and risks associated with potential skin sensitizers.

Cosmetics Europe compilation of historical serious eye damage/eye irritation in vivo data analysed by drivers of classification to support the selection of chemicals for development and evaluation of alternative methods/strategies: the Draize eye test Reference Database (DRD).

A thorough understanding of which of the effects assessed in the in vivo Draize eye test are responsible for driving UN GHS/EU CLP classification is critical for an adequate selection of chemicals to be used in the development and/or evaluation of alternative methods/strategies and for properly assessing their predictive capacity and limitations. For this reason, Cosmetics Europe has compiled a database of Draize data (Draize eye test Reference Database, DRD) from external lists that were created to support past validation activities. This database contains 681 independent in vivo studies on 634 individual chemicals representing a wide range of chemical classes. A description of all the ocular effects observed in vivo, i.e. degree of severity and persistence of corneal opacity (CO), iritis, and/or conjunctiva effects, was added for each individual study in the database, and the studies were categorised according to their UN GHS/EU CLP classification and the main effect driving the classification. An evaluation of the various in vivo drivers of classification compiled in the database was performed to establish which of these are most important from a regulatory point of view. These analyses established that the most important drivers for Cat 1 Classification are (1) CO mean ≥ 3 (days 1-3) (severity) and (2) CO persistence on day 21 in the absence of severity, and those for Cat 2 classification are (3) CO mean ≥ 1 and (4) conjunctival redness mean ≥ 2. Moreover, it is shown that all classifiable effects (including persistence and CO = 4) should be present in ≥60 % of the animals to drive a classification. As a consequence, our analyses suggest the need for a critical revision of the UN GHS/EU CLP decision criteria for the Cat 1 classification of chemicals. Finally, a number of key criteria are identified that should be taken into consideration when selecting reference chemicals for the development, evaluation and/or validation of alternative methods and/or strategies for serious eye damage/eye irritation testing. Most important, the DRD is an invaluable tool for any future activity involving the selection of reference chemicals.

Practical Aspects of Designing and Conducting Validation Studies Involving Multi-study Trials.

This chapter focuses on practical aspects of conducting prospective in vitro validation studies, and in particular, by laboratories that are members of the European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) that is coordinated by the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). Prospective validation studies involving EU-NETVAL, comprising a multi-study trial involving several laboratories or "test facilities", typically consist of two main steps: (1) the design of the validation study by EURL ECVAM and (2) the execution of the multi-study trial by a number of qualified laboratories within EU-NETVAL, coordinated and supported by EURL ECVAM. The approach adopted in the conduct of these validation studies adheres to the principles described in the OECD Guidance Document on the Validation and International Acceptance of new or updated test methods for Hazard Assessment No. 34 (OECD 2005). The context and scope of conducting prospective in vitro validation studies is dealt with in Chap. 4 . Here we focus mainly on the processes followed to carry out a prospective validation of in vitro methods involving different laboratories with the ultimate aim of generating a dataset that can support a decision in relation to the possible development of an international test guideline (e.g. by the OECD) or the establishment of performance standards.

International Harmonization and Cooperation in the Validation of Alternative Methods.

The development and validation of scientific alternatives to animal testing is important not only from an ethical perspective (implementation of 3Rs), but also to improve safety assessment decision making with the use of mechanistic information of higher relevance to humans. To be effective in these efforts, it is however imperative that validation centres, industry, regulatory bodies, academia and other interested parties ensure a strong international cooperation, cross-sector collaboration and intense communication in the design, execution, and peer review of validation studies. Such an approach is critical to achieve harmonized and more transparent approaches to method validation, peer-review and recommendation, which will ultimately expedite the international acceptance of valid alternative methods or strategies by regulatory authorities and their implementation and use by stakeholders. It also allows achieving greater efficiency and effectiveness by avoiding duplication of effort and leveraging limited resources. In view of achieving these goals, the International Cooperation on Alternative Test Methods (ICATM) was established in 2009 by validation centres from Europe, USA, Canada and Japan. ICATM was later joined by Korea in 2011 and currently also counts with Brazil and China as observers. This chapter describes the existing differences across world regions and major efforts carried out for achieving consistent international cooperation and harmonization in the validation and adoption of alternative approaches to animal testing.

Probe and Sensors Development for Level Measurement of Fats, Oils and Grease in Grease Boxes.

The wide spread of food outlets has become an environmental and sanitation infrastructure problem, due to Fats, Oils and Grease (FOG). A grease box is used at the industrials facilities to collect the FOG, in a specific time window, while its quality is good for recycling (e.g., biodiesel) and it is economically valuable. After this period, it will be disposed at a cost. For the proper management of the grease boxes, it is necessary to know the quantity of FOG inside the boxes, which is a major problem, as the boxes are sealed and permanently filled with water. The lack of homogeneity of the FOG renders it not detectable by current probes for level detection in liquids. In this article, the design, development and testing of a set of probes for FOG level measurement, based on the principles used in sensors for the detection of liquids inside containers, is described. The most suitable probe, based on the capacitance principle, together with the necessary hardware and software modules for data acquisition and transmission, was developed and tested. After the development phase, the probe was integrated on a metropolitan system for FOG collection and grease box management in partnership with a grease box management company.

Retrospective analysis of the Draize test for serious eye damage/eye irritation: importance of understanding the in vivo endpoints under UN GHS/EU CLP for the development and evaluation of in vitro test methods.

For more than two decades, scientists have been trying to replace the regulatory in vivo Draize eye test by in vitro methods, but so far only partial replacement has been achieved. In order to better understand the reasons for this, historical in vivo rabbit data were analysed in detail and resampled with the purpose of (1) revealing which of the in vivo endpoints are most important in driving United Nations Globally Harmonized System/European Union Regulation on Classification, Labelling and Packaging (UN GHS/EU CLP) classification for serious eye damage/eye irritation and (2) evaluating the method's within-test variability for proposing acceptable and justifiable target values of sensitivity and specificity for alternative methods and their combinations in testing strategies. Among the Cat 1 chemicals evaluated, 36-65 % (depending on the database) were classified based only on persistence of effects, with the remaining being classified mostly based on severe corneal effects. Iritis was found to rarely drive the classification (<4 % of both Cat 1 and Cat 2 chemicals). The two most important endpoints driving Cat 2 classification are conjunctiva redness (75-81 %) and corneal opacity (54-75 %). The resampling analyses demonstrated an overall probability of at least 11 % that chemicals classified as Cat 1 by the Draize eye test could be equally identified as Cat 2 and of about 12 % for Cat 2 chemicals to be equally identified as No Cat. On the other hand, the over-classification error for No Cat and Cat 2 was negligible (<1 %), which strongly suggests a high over-predictive power of the Draize eye test. Moreover, our analyses of the classification drivers suggest a critical revision of the UN GHS/EU CLP decision criteria for the classification of chemicals based on Draize eye test data, in particular Cat 1 based only on persistence of conjunctiva effects or corneal opacity scores of 4. In order to successfully replace the regulatory in vivo Draize eye test, it will be important to recognise these uncertainties and to have in vitro tools to address the most important in vivo endpoints identified in this paper.