AW0521 - Determining potential impacts of Precision Breeding on Animal Welfare FINAL REPORT

1. Introduction of the Genetic Technology (Precision Breeding) Act in 2023 paved the way for the use of precision breeding technologies (e.g., genome editing) in livestock in England. However, while recognising that there may be major benefits inferred by increased disease resistance and other traits, concern has been raised about the possible wider effects of the use of the technology on animal welfare. This project aimed to understand the current situation with respect to level of use and development of precision-bred animals and to consider what welfare indicators should be used to assess welfare in general, and for specific types of edits.2. A mapping and scoping phase indicated that few companies have initiated data collection or development of precision-bred animals that might be present in/be imported into England. The pig and fish sectors were the only sectors to indicate that development has commenced. Mapping suggested that the first animals are bred in research/university environments where animals are kept under the auspices of ASPA. Apart from the fish and pig sectors, the chicken, cattle and sheep sectors also expressed some interest in developing precision-bred animals in the near future (I.e.., in the next 5 years). For the equine sector, only a few stakeholders expressed some interest in using precison-breeding technologies to improve specific traits such as disease resistance or resilience to environmental stress, but there is no intention to use PB in equine breeding practice in the immediate future. 3. Expert consultation and a review of the literature indicated that the Five Domains Model was the most appropriate of current animal welfare models to use to build indicator lists. This model includes nutritional state, health, environmental responses, behavioural interactions and mental state. While most animal welfare assessment protocols assess the effects of housing and management on welfare outcomes for animals, it is biological functioning that is the most important aspect to assess in the precision breeding context.4. Welfare assessment indicator lists were drawn up for the three main species that are in the most advanced stage of use of precision breeding. These were pigs, poultry and salmon. Indicator lists were constructed that drew on industry handbooks, current animal welfare assessment schemes and relevant literature. These indicator lists aimed to facilitate a holistic assessment of overall animal welfare to detect changes in functioning across the Five Domains. The indicator lists contain welfare indicators that assess the animal across its EVID4 Evidence Project Final Report (Rev. 06/11) Page 3 of 21lifetime, compared with a control group of the same breed and same age and sex ratio. Three levels of assessment were considered: basic, enhanced and enhanced plus. The basic level of assessment does not fully cover the five domains in all three species, so SRUC strongly recommends that the enhanced level of assessment is adopted.5. In addition to the overall welfare assessment indicator lists, three cases studies were considered to determine how and when to add additional welfare indicators to these lists. The aim was to cover welfare-related traits and production-relate traits. To this end, the specific traits considered were PRRS virus, avian influenza and the hypothetical case of myostatin in fish. As animals carrying these edits are not available for inspection, a risk assessment was limited to ‘consequence characterisation’: ie., identifying possible consequences of gene editing on welfare. These case studies showed that a wider consideration of the edit and the pathways involved needs to be investigated. In addition to the overall holistic assessment using the Basic, Enhanced or Enhanced Plus levels, assessment using additional welfare indicators that are relevant to the specific edit may be required.6. Three webinars/workshops were held to present results to stakeholders. In addition, a meeting was held with equine stakeholders and numerous discussions were held with individual stakeholders to gain information on aspects of precision breeding

AW0521 - Determining potential impacts of Precision Breeding on Animal Welfare FINAL REPORT

1. Introduction of the Genetic Technology (Precision Breeding) Act in 2023 paved the way for the use of precision breeding technologies (e.g., genome editing) in livestock in England. However, while recognising that there may be major benefits inferred by increased disease resistance and other traits, concern has been raised about the possible wider effects of the use of the technology on animal welfare. This project aimed to understand the current situation with respect to level of use and development of precision-bred animals and to consider what welfare indicators should be used to assess welfare in general, and for specific types of edits.2. A mapping and scoping phase indicated that few companies have initiated data collection or development of precision-bred animals that might be present in/be imported into England. The pig and fish sectors were the only sectors to indicate that development has commenced. Mapping suggested that the first animals are bred in research/university environments where animals are kept under the auspices of ASPA. Apart from the fish and pig sectors, the chicken, cattle and sheep sectors also expressed some interest in developing precision-bred animals in the near future (I.e.., in the next 5 years). For the equine sector, only a few stakeholders expressed some interest in using precison-breeding technologies to improve specific traits such as disease resistance or resilience to environmental stress, but there is no intention to use PB in equine breeding practice in the immediate future. 3. Expert consultation and a review of the literature indicated that the Five Domains Model was the most appropriate of current animal welfare models to use to build indicator lists. This model includes nutritional state, health, environmental responses, behavioural interactions and mental state. While most animal welfare assessment protocols assess the effects of housing and management on welfare outcomes for animals, it is biological functioning that is the most important aspect to assess in the precision breeding context.4. Welfare assessment indicator lists were drawn up for the three main species that are in the most advanced stage of use of precision breeding. These were pigs, poultry and salmon. Indicator lists were constructed that drew on industry handbooks, current animal welfare assessment schemes and relevant literature. These indicator lists aimed to facilitate a holistic assessment of overall animal welfare to detect changes in functioning across the Five Domains. The indicator lists contain welfare indicators that assess the animal across its EVID4 Evidence Project Final Report (Rev. 06/11) Page 3 of 21lifetime, compared with a control group of the same breed and same age and sex ratio. Three levels of assessment were considered: basic, enhanced and enhanced plus. The basic level of assessment does not fully cover the five domains in all three species, so SRUC strongly recommends that the enhanced level of assessment is adopted.5. In addition to the overall welfare assessment indicator lists, three cases studies were considered to determine how and when to add additional welfare indicators to these lists. The aim was to cover welfare-related traits and production-relate traits. To this end, the specific traits considered were PRRS virus, avian influenza and the hypothetical case of myostatin in fish. As animals carrying these edits are not available for inspection, a risk assessment was limited to ‘consequence characterisation’: ie., identifying possible consequences of gene editing on welfare. These case studies showed that a wider consideration of the edit and the pathways involved needs to be investigated. In addition to the overall holistic assessment using the Basic, Enhanced or Enhanced Plus levels, assessment using additional welfare indicators that are relevant to the specific edit may be required.6. Three webinars/workshops were held to present results to stakeholders. In addition, a meeting was held with equine stakeholders and numerous discussions were held with individual stakeholders to gain information on aspects of precision breeding

Quantum invariants and the graph isomorphism problem

© 2019 authors. Published by the American Physical Society. Three graph invariants are introduced which may be measured from a quantum graph state and form examples of a framework under which other graph invariants can be constructed. Each invariant is based on distinguishing a different number of qubits. This is done by applying different measurements to the qubits to be distinguished. The performance of these invariants is evaluated and compared to classical invariants. We verify that the invariants can distinguish all nonisomorphic graphs with nine or fewer nodes. The invariants have also been applied to "classically hard" strongly regular graphs, successfully distinguishing all strongly regular graphs of up to 29 nodes, and preliminarily to weighted graphs. We have found that, although it is possible to prepare states with a polynomial number of operations, the average number of preparations required to distinguish nonisomorphic graph states scales exponentially with the number of nodes. We have so far been unable to find operators which reliably compare graphs and reduce the required number of preparations to feasible levels

The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

From Macroscopic to Microscopic: Experimental and Computational Methods to Investigate Bio-tribology

Tribology is an important factor (among other factors) during biological interactions of devices and tissues. The paper discusses how new computational and experimental methods can be used to understand and improve the design and development of medical devices at macro and micro scales to sustain life beyond 50 years. We have used pre-clinical experiments and computational methods to understand interactions between orthopaedic implants at the macro scale. The computational model has been validated with experiments. Now this computational model can predict damage in implants for different patients. One such application was successfully tried and tested in collaboration with University National Autonomous Mexico. This methodology can be used in future to design patient specific, affordable (using 3D printing) and robust implants which will be useful for developing countries like Vietnam, India and Mexico. Improvement of catheter designs is important to reduce damage to the internal tissues while being used for cardiovascular problems. We are developing new experimental techniques (in micro scale) that can be used to understand the interaction of cells with the catheter material. These will help reduce the hospital costs incurred during longer stay of the patients admitted for cardiovascular related problems

Reliability and validity of three questionnaires measuring context-specific sedentary behaviour and associated correlates in adolescents, adults and older adults

BACKGROUND: Reliable and valid measures of total sedentary time, context-specific sedentary behaviour (SB) and its potential correlates are useful for the development of future interventions. The purpose was to examine test-retest reliability and criterion validity of three newly developed questionnaires on total sedentary time, context-specific SB and its potential correlates in adolescents, adults and older adults. METHODS: Reliability and validity was tested in six different samples of Flemish (Belgium) residents. For the reliability study, 20 adolescents, 22 adults and 20 older adults filled out the age-specific SB questionnaire twice. Test-retest reliability was analysed using Kappa coefficients, Intraclass Correlation Coefficients and/or percentage agreement, separately for the three age groups. For the validity study, data were retrieved from 62 adolescents, 33 adults and 33 older adults, with activPAL as criterion measure. Spearman correlations and Bland-Altman plots (or non-parametric approach) were used to analyse criterion validity, separately for the three age groups and for weekday, weekend day and average day. RESULTS: The test-retest reliability for self-reported total sedentary time indicated following values: ICC = 0.37-0.67 in adolescents; ICC = 0.73-0.77 in adults; ICC = 0.68-0.80 in older adults. Item-specific reliability results (e.g. context-specific SB and its potential correlates) showed good-to-excellent reliability in 67.94%, 68.90% and 66.38% of the items in adolescents, adults and older adults respectively. All items belonging to sedentary-related equipment and simultaneous SB showed good reliability. The sections of the questionnaire with lowest reliability were: context-specific SB (adolescents), potential correlates of computer use (adults) and potential correlates of motorized transport (older adults). Spearman correlations between self-reported total sedentary time and the activPAL were different for each age group: rho = 0.02-0.42 (adolescents), rho = 0.06-0.52 (adults), rho = 0.38-0.50 (older adults). Participants over-reported total sedentary time (except for weekend day in older adults) compared to the activPAL, for weekday, weekend day and average day respectively by +57.05%, +46.29%, +53.34% in adolescents; +40.40%, +19.15%, +32.89% in adults; +10.10%, -6.24%, +4.11% in older adults. CONCLUSIONS: The questionnaires showed acceptable test-retest reliability and criterion validity. However, over-reporting of total SB was noticeable in adolescents and adults. Nevertheless, these questionnaires will be useful in getting context-specific information on SB