Computational Study of the Kinetics and Mechanisms of Gas-Phase Decomposition of N-Diacetamides Using Density Functional Theory.

In this research work, we examined the decomposition mechanisms of N-substituted diacetamides. We focused on the substituent effect on the nitrogen lone-pair electron delocalization, with electron-withdrawing and electron donor groups. DFT functionals used the following: B1LYP, B3PW91, CAMB3LYP, LC-BLYP, and X3LYP. Dispersion corrections (d3bj) with Becke-Johnson damping were applied when necessary to improve non-covalent interactions in the transition state. Pople basis sets with higher angular moments and def2-TZVP basis sets were also applied and were crucial for obtaining consistent thermodynamic parameters. The proposed mechanism involves a six-membered transition state with the extraction of an α hydrogen. Several conformers of N-diacetamides were used to account for the decrease in entropy in the transition state in the rate-determining state. All calculations, including natural bond orbital (NBO) analyses, were performed using the Gaussian16 computational package and its GaussView 6.0 visualizer, along with VMD and GNUPLOT software. The isosurfaces and IBSIs were calculated using MultiWFN and IGMPlot, respectively.

Aortoesophageal fistula as a fatal complication of esophageal perforation.

Aortoesophageal fistula is a very rare cause of upper gastrointestinal bleeding, however its interest lies in the high mortality rate associated with it. Due to this, early diagnosis and treatment of this entity is essential to increase survival. The typical symptoms known as the Chiari´s triad are only present in 45% of reported cases. We present the case of a patient with upper gastrointestinal bleeding due to an aortoesophageal fistula as well as the importance of endoscopic use for its differential diagnosis.

3D-Printed Liquid Cell Resonator with Piezoelectric Actuation for In-Line Density-Viscosity Measurements.

The in-line monitoring of liquid properties, such as density and viscosity, is a key process in many industrial areas such as agro-food, automotive or biotechnology, requiring real-time automation, low-cost and miniaturization, while maintaining a level of accuracy and resolution comparable to benchtop instruments. In this paper, 3D-printed cuboid-shaped liquid cells featuring a rectangular vibrating plate in one of the sides, actuated by PZT piezoelectric layers, were designed, fabricated and tested. The device was resonantly excited in the 3rd-order roof tile-shaped vibration mode of the plate and validated as a density-viscosity sensor. Furthermore, conditioning circuits were designed to adapt the impedance of the resonator and to cancel parasitic effects. This allowed us to implement a phase-locked loop-based oscillator circuit whose oscillation frequency and voltage amplitude could be calibrated against density and viscosity of the liquid flowing through the cell. To demonstrate the performance, the sensor was calibrated with a set of artificial model solutions of grape must, representing stages of a wine fermentation process. Our results demonstrate the high potential of the low-cost sensor to detect the decrease in sugar and the increase in ethanol concentrations during a grape must fermentation, with a resolution of 10 µg/mL and 3 µPa·s as upper limits for the density and viscosity, respectively.

Improving the prediction of acute myeloid leukaemia outcomes by complementing mutational profiling with ex vivo chemosensitivity.

Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia (AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combined strategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widely used drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identified an adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3·29, P < 0·0001]. A high correlation was found between the ex vivo PharmaFlow results and clinical induction response (69%). Clinical correlation analysis showed that the pattern of multiresistance revealed by ex vivo PharmaFlow identified patients with a high risk of death (HR: 2·58). Patients with mutation status also ran a high risk (HR 4·19), and the risk was increased further in patients with both adverse profiles (HR 4·82). We have developed a new score based on NGS and ex vivo drug testing for AML patients that improves upon current prognostic risk stratification and allows clinicians to tailor treatments to minimise drug resistance.

A Geometrical Study on the Roof Tile-Shaped Modes in AlN-Based Piezoelectric Microcantilevers as Viscosity⁻Density Sensors.

Cantilever resonators based on the roof tile-shaped modes have recently demonstrated their suitability for liquid media monitoring applications. The early studies have shown that certain combinations of dimensions and order of the mode can maximize the Q-factor, what might suggest a competition between two mechanisms of losses with different geometrical dependence. To provide more insight, a comprehensive study of the Q-factor and the resonant frequency of these modes in microcantilever resonators with lengths and widths between 250 and 3000 µm and thicknesses between 10 and 60 µm is presented. These modes can be efficiently excited by a thin piezoelectric AlN film and a properly designed top electrode layout. The electrical and optical characterization of the resonators are performed in liquid media and then their performance is evaluated in terms of quality factor and resonant frequency. A quality factor as high as 140 was measured in isopropanol for a 1000 × 900 × 10 µm³ cantilever oscillating in the 11th order roof tile-shaped mode at 4 MHz; density and viscosity resolutions of 10-6 g/mL and 10-4 mPa·s, respectively are estimated for a geometrically optimized cantilever resonating below 1 MHz.

The use of high expansion foam for stunning and killing pigs and poultry.

The EFSA Panel on Animal Health and Welfare (AHAW) was asked to deliver a scientific opinion on the use of high-expansion foam for stunning and killing pigs and poultry. A dossier was provided by the applicant as the basis for an assessment of the extent to which the method is able to provide a level of animal welfare at least equivalent to that ensured by the currently allowed methods for pigs and poultry. According to legislation, to be approved in the EU, new stunning methods must ensure (1) the absence of pain, distress or suffering until the onset of unconsciousness, and (2) that the animal remains unconscious until death. An ad hoc Working Group set up by EFSA performed the assessment as follows: (1) The data provided were checked against the criteria laid down in the EFSA Guidance (EFSA, 2018), and was found to partially fulfil those criteria; (2) extensive literature search; (3) data extraction for quantitative assessment; (4) qualitative exercise based on non-formal expert elicitation. The assessment led to conclude that it is more likely than not (certainty > 50%-100%) that high-expansion foam for stunning and killing pigs and poultry, named NEFS in container (Nitrogen Expansion Foam Stunning in container), provides a level of welfare at least equivalent to one or more of the currently allowed methods listed in Annex I of Council Regulation (EC) No 1099/2009. The overall assessment of EFSA is valid only under the technical conditions described in this Opinion for laying hens, broiler chickens of all age and pigs weighing 15-41 kg in situations other than slaughter. The overall assessment of EFSA is that NEFS can be suitable for depopulation using containers for pig and poultry farms respecting the technical conditions and the categories and types of animals defined in this Scientific Opinion.

Welfare of sheep and goats during killing for purposes other than slaughter.

Sheep and goats of different ages may have to be killed on-farm for purposes other than slaughter (where slaughter is defined as killing for human consumption) either individually (i.e. on-farm killing of unproductive, injured or terminally ill animals) or on a large scale (i.e. depopulation for disease control purposes and for other situations, such as environmental contamination and disaster management) outside the slaughterhouses. The purpose of this opinion was to assess the hazards and welfare consequences associated with the on-farm killing of sheep and goats. The whole killing procedure was divided into Phase 1 (pre-killing) - that included the processes (i) handling and moving the animals to the killing place and (ii) restraint of the animals before application of the killing methods and Phase 2 - that included stunning and killing of the animals. The killing methods for sheep and goats were grouped into three categories: (1) mechanical, (2) electrical and (3) lethal injection. Welfare consequences that sheep and goats may experience during each process were identified (e.g. handling stress, restriction of movements and tissue lesions during restraint) and animal-based measures (ABMs) to assess them were proposed. During application of the killing method, sheep and goats will experience pain and fear if they are ineffectively stunned or if they recover consciousness. ABMs related to the state of consciousness can be used to indirectly assess pain and fear. Flowcharts including ABMs for consciousness specific to each killing method were included in the opinion. Possible welfare hazards were identified for each process, together with their origin and related preventive and corrective measures. Outcome tables linking hazards, welfare consequences, ABMs, origins, preventive and corrective measures were developed for each process. Mitigation measures to minimise welfare consequences were proposed.

Vaccination of poultry against highly pathogenic avian influenza - Part 2. Surveillance and mitigation measures.

Selecting appropriate diagnostic methods that take account of the type of vaccine used is important when implementing a vaccination programme against highly pathogenic avian influenza (HPAI). If vaccination is effective, a decreased viral load is expected in the samples used for diagnosis, making molecular methods with high sensitivity the best choice. Although serological methods can be reasonably sensitive, they may produce results that are difficult to interpret. In addition to routine molecular monitoring, it is recommended to conduct viral isolation, genetic sequencing and phenotypic characterisation of any HPAI virus detected in vaccinated flocks to detect escape mutants early. Following emergency vaccination, various surveillance options based on virological testing of dead birds ('bucket sampling') at defined intervals were assessed to be effective for early detection of HPAIV and prove disease freedom in vaccinated populations. For ducks, virological or serological testing of live birds was assessed as an effective strategy. This surveillance could be also applied in the peri-vaccination zone on vaccinated establishments, while maintaining passive surveillance in unvaccinated chicken layers and turkeys, and weekly bucket sampling in unvaccinated ducks. To demonstrate disease freedom with > 99% confidence and to detect HPAI virus sufficiently early following preventive vaccination, monthly virological testing of all dead birds up to 15 per flock, coupled with passive surveillance in both vaccinated and unvaccinated flocks, is recommended. Reducing the sampling intervals increases the sensitivity of early detection up to 100%. To enable the safe movement of vaccinated poultry during emergency vaccination, laboratory examinations in the 72 h prior to the movement can be considered as a risk mitigation measure, in addition to clinical inspection; sampling results from existing surveillance activities carried out in these 72 h could be used. In this Opinion, several schemes are recommended to enable the safe movement of vaccinated poultry following preventive vaccination.

Editorial for the Special Issue on Piezoelectric Transducers: Materials, Devices and Applications, Volume III.

This is the third volume of a Special Issue focused on piezoelectric transducers, covering a wide range of topics, including the design, fabrication, characterization, packaging and system integration or final applications of mili/micro/nano-electro-mechanical system-based transducers featuring piezoelectric materials and devices [...].

SARS-CoV-2 in animals: susceptibility of animal species, risk for animal and public health, monitoring, prevention and control.

The epidemiological situation of SARS-CoV-2 in humans and animals is continually evolving. To date, animal species known to transmit SARS-CoV-2 are American mink, raccoon dog, cat, ferret, hamster, house mouse, Egyptian fruit bat, deer mouse and white-tailed deer. Among farmed animals, American mink have the highest likelihood to become infected from humans or animals and further transmit SARS-CoV-2. In the EU, 44 outbreaks were reported in 2021 in mink farms in seven MSs, while only six in 2022 in two MSs, thus representing a decreasing trend. The introduction of SARS-CoV-2 into mink farms is usually via infected humans; this can be controlled by systematically testing people entering farms and adequate biosecurity. The current most appropriate monitoring approach for mink is the outbreak confirmation based on suspicion, testing dead or clinically sick animals in case of increased mortality or positive farm personnel and the genomic surveillance of virus variants. The genomic analysis of SARS-CoV-2 showed mink-specific clusters with a potential to spill back into the human population. Among companion animals, cats, ferrets and hamsters are those at highest risk of SARS-CoV-2 infection, which most likely originates from an infected human, and which has no or very low impact on virus circulation in the human population. Among wild animals (including zoo animals), mostly carnivores, great apes and white-tailed deer have been reported to be naturally infected by SARS-CoV-2. In the EU, no cases of infected wildlife have been reported so far. Proper disposal of human waste is advised to reduce the risks of spill-over of SARS-CoV-2 to wildlife. Furthermore, contact with wildlife, especially if sick or dead, should be minimised. No specific monitoring for wildlife is recommended apart from testing hunter-harvested animals with clinical signs or found-dead. Bats should be monitored as a natural host of many coronaviruses.

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) 2016/429): infection with Gyrodactylus salaris (GS).

Infection with Gyrodactylus salaris was assessed according to the criteria of the Animal Health Law (AHL), in particular, the criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as laid down in Article 9 and Article 8 for listing animal species related to infection with G. salaris. The assessment was performed following the ad hoc method for data collection and assessment previously developed by AHAW panel and already published. The outcome reported is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with an uncertain outcome. According to the assessment here performed, it is uncertain whether infection with G. salaris can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (33-70% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that Infection with G. salaris does not meet the criteria in Section 1 and 3 (Category A and C; 1-5% and 10-33% probability of fulfilling the criteria, respectively) and it is uncertain whether it meets the criteria in Sections 2, 4 and 5 (Categories B, D and E; 33-80%, 33-66% and 33-80% probability of meeting the criteria, respectively). The animal species to be listed for infection with G. salaris according to Article 8 criteria are provided.

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) 2016/429): Bacterial kidney disease (BKD).

Bacterial kidney disease (BKD) was assessed according to the criteria of the Animal Health Law (AHL), in particular the criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as laid out in Article 9 and Article 8 for listing animal species related to BKD. The assessment was performed following the ad hoc method on data collection and assessment developed by AHAW Panel and already published. The outcome reported is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with an uncertain outcome. According to this assessment, BKD can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (66-90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that BKD does not meet the criteria in Sections 1, 2 and 3 (Categories A, B and C; 1-5%, 33-66% and 33-66% probability of meeting the criteria, respectively) but meets the criteria in Sections 4 and 5 (Categories D and E; 66-90% and 66-90% probability of meeting the criteria, respectively). The animal species to be listed for BKD according to Article 8 criteria are provided.

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU)2016/429): Infection with salmonid alphavirus (SAV).

Infection with salmonid alphavirus (SAV) was assessed according to the criteria of the Animal Health Law (AHL), in particular the criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as laid out in Article 9 and Article 8 for listing animal species related to infection with SAV. The assessment was performed following the ad hoc method on data collection and assessment developed by AHAW Panel and already published. The outcome reported is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with an uncertain outcome. According to the assessment, it was uncertain whether infection with salmonid alphavirus can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (50-80% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that infection with salmonid alphavirus does not meet the criteria in Section 1 (Category A; 5-10% probability of meeting the criteria) and it is uncertain whether it meets the criteria in Sections 2, 3, 4 and 5 (Categories B, C, D and E; 50-90%, probability of meeting the criteria). The animal species to be listed for infection with SAV according to Article 8 criteria are provided.

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) 2016/429): Spring Viraemia of Carp (SVC).

Spring Viraemia of Carp (SVC) was assessed according to the criteria of the Animal Health Law (AHL), in particular the criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to SVC. The assessment was performed following the ad hoc method for data collection and assessment previously developed by the AHAW panel and already published. The outcome reported is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with an uncertain outcome. According to the assessment performed here, it is uncertain whether SVC can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (45-90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that SVC does not meet the criteria in Section 1 (Category A; 5-33% probability of meeting the criteria) and it is uncertain whether it meets the criteria in Sections 2, 3, 4 and 5 (Categories B, C, D and E; 33-66%, 10-66%, 45-90% and 45-90% probability of meeting the criteria, respectively). The animal species to be listed for SVC according to Article 8 criteria are provided.

Vaccination of poultry against highly pathogenic avian influenza - part 1. Available vaccines and vaccination strategies.

Several vaccines have been developed against highly pathogenic avian influenza (HPAI), mostly inactivated whole-virus vaccines for chickens. In the EU, one vaccine is authorised in chickens but is not fully efficacious to stop transmission, highlighting the need for vaccines tailored to diverse poultry species and production types. Off-label use of vaccines is possible, but effectiveness varies. Vaccines are usually injectable, a time-consuming process. Mass-application vaccines outside hatcheries remain rare. First vaccination varies from in-ovo to 6 weeks of age. Data about immunity onset and duration in the target species are often unavailable, despite being key for effective planning. Minimising antigenic distance between vaccines and field strains is essential, requiring rapid updates of vaccines to match circulating strains. Generating harmonised vaccine efficacy data showing vaccine ability to reduce transmission is crucial and this ability should be also assessed in field trials. Planning vaccination requires selecting the most adequate vaccine type and vaccination scheme. Emergency protective vaccination is limited to vaccines that are not restricted by species, age or pre-existing vector-immunity, while preventive vaccination should prioritise achieving the highest protection, especially for the most susceptible species in high-risk transmission areas. Model simulations in France, Italy and The Netherlands revealed that (i) duck and turkey farms are more infectious than chickens, (ii) depopulating infected farms only showed limitations in controlling disease spread, while 1-km ring-culling performed better than or similar to emergency preventive ring-vaccination scenarios, although with the highest number of depopulated farms, (iii) preventive vaccination of the most susceptible species in high-risk transmission areas was the best option to minimise the outbreaks' number and duration, (iv) during outbreaks in such areas, emergency protective vaccination in a 3-km radius was more effective than 1- and 10-km radius. Vaccine efficacy should be monitored and complement other surveillance and preventive efforts.

Welfare of broilers on farm.

This Scientific Opinion considers the welfare of domestic fowl (Gallus gallus) related to the production of meat (broilers) and includes the keeping of day-old chicks, broiler breeders, and broiler chickens. Currently used husbandry systems in the EU are described. Overall, 19 highly relevant welfare consequences (WCs) were identified based on severity, duration and frequency of occurrence: 'bone lesions', 'cold stress', 'gastro-enteric disorders', 'group stress', 'handling stress', 'heat stress', 'isolation stress', 'inability to perform comfort behaviour', 'inability to perform exploratory or foraging behaviour', 'inability to avoid unwanted sexual behaviour', 'locomotory disorders', 'prolonged hunger', 'prolonged thirst', 'predation stress', 'restriction of movement', 'resting problems', 'sensory under- and overstimulation', 'soft tissue and integument damage' and 'umbilical disorders'. These WCs and their animal-based measures (ABMs) that can identify them are described in detail. A variety of hazards related to the different husbandry systems were identified as well as ABMs for assessing the different WCs. Measures to prevent or correct the hazards and/or mitigate each of the WCs are listed. Recommendations are provided on quantitative or qualitative criteria to answer specific questions on the welfare of broilers and related to genetic selection, temperature, feed and water restriction, use of cages, light, air quality and mutilations in breeders such as beak trimming, de-toeing and comb dubbing. In addition, minimal requirements (e.g. stocking density, group size, nests, provision of litter, perches and platforms, drinkers and feeders, of covered veranda and outdoor range) for an enclosure for keeping broiler chickens (fast-growing, slower-growing and broiler breeders) are recommended. Finally, 'total mortality', 'wounds', 'carcass condemnation' and 'footpad dermatitis' are proposed as indicators for monitoring at slaughter the welfare of broilers on-farm.

Welfare of calves.

This Scientific Opinion addresses a European Commission request on the welfare of calves as part of the Farm to Fork strategy. EFSA was asked to provide a description of common husbandry systems and related welfare consequences, as well as measures to prevent or mitigate the hazards leading to them. In addition, recommendations on three specific issues were requested: welfare of calves reared for white veal (space, group housing, requirements of iron and fibre); risk of limited cow-calf contact; and animal-based measures (ABMs) to monitor on-farm welfare in slaughterhouses. The methodology developed by EFSA to address similar requests was followed. Fifteen highly relevant welfare consequences were identified, with respiratory disorders, inability to perform exploratory or foraging behaviour, gastroenteric disorders and group stress being the most frequent across husbandry systems. Recommendations to improve the welfare of calves include increasing space allowance, keeping calves in stable groups from an early age, ensuring good colostrum management and increasing the amounts of milk fed to dairy calves. In addition, calves should be provided with deformable lying surfaces, water via an open surface and long-cut roughage in racks. Regarding specific recommendations for veal systems, calves should be kept in small groups (2-7 animals) within the first week of life, provided with ~ 20 m2/calf and fed on average 1 kg neutral detergent fibre (NDF) per day, preferably using long-cut hay. Recommendations on cow-calf contact include keeping the calf with the dam for a minimum of 1 day post-partum. Longer contact should progressively be implemented, but research is needed to guide this implementation in practice. The ABMs body condition, carcass condemnations, abomasal lesions, lung lesions, carcass colour and bursa swelling may be collected in slaughterhouses to monitor on-farm welfare but should be complemented with behavioural ABMs collected on farm.

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): infectious pancreatic necrosis (IPN).

Infectious pancreatic necrosis (IPN) was assessed according to the criteria of the Animal Health Law (AHL), in particular, the criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9, and Article 8 for listing animal species related to IPN. The assessment was performed following a methodology previously published. The outcome reported is the median of the probability ranges provided by the experts, which indicates whether each criterion is fulfilled (lower bound ≥ 66%) or not (upper bound ≤ 33%), or whether there is uncertainty about fulfilment. Reasoning points are reported for criteria with an uncertain outcome. According to the assessment here performed, it is uncertain whether IPN can be considered eligible to be listed for Union intervention according to Article 5 of the AHL (50-90% probability). According to the criteria in Annex IV, for the purpose of categorisation related to the level of prevention and control as in Article 9 of the AHL, the AHAW Panel concluded that IPN does not meet the criteria in Section 1 (Category A; 0-1% probability of meeting the criteria) and it is uncertain whether it meets the criteria in Sections 2, 3, 4 and 5 (Categories B, C, D and E; 33-66%, 33-66%, 50-90% and 50-99% probability of meeting the criteria, respectively). The animal species to be listed for IPN according to Article 8 criteria are provided.