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

Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio

Combined effects of time spent in physical activity, sedentary behaviors and sleep on obesity and cardio-metabolic health markers: a novel compositional data analysis approach

<div><p>The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity.</p></div

Case–control study of lifetime total physical activity and endometrial cancer risk

A population-based case–control study of physical activity and endometrial cancer risk was conducted in Alberta between 2002 and 2006. Incident, histologically confirmed cases of endometrial cancer (n = 542) were frequency age-matched to controls (n = 1,032). The Lifetime Total Physical Activity Questionnaire was used to measure occupational, household, and recreational activity levels. Multivariable logistic regression analyses were conducted. Total lifetime physical activity reduced endometrial cancer risk (odds ratio [OR] for >129 vs. <82 MET-h/week/year = 0.86, 95% confidence interval [95% CI]: 0.63, 1.18). By type of activity, the risks were significantly decreased for greater recreational activity (OR = 0.64, 95% CI: 0.47, 0.87), but not for household activity (OR = 1.09, 95% CI: 0.75, 1.58) and/or occupational activity (OR = 0.90, 95% CI: 0.67, 1.20) when comparing the highest to lowest quartiles. For activity performed at different biologically defined life periods, some indication of reduced risks with activity done between menarche and full-term pregnancy and after menarche was observed. When examining the activity by intensity of activity (i.e., light <3, moderate 3–6, and vigorous >6 METs), light activity slightly decreased endometrial cancer risk (OR = 0.68, 95% CI: 0.48, 0.97) but no association with moderate or vigorous intensity activity was found. Endometrial cancer risk was increased with sedentary occupational activity by 28% (95 CI%: 0.89, 1.83) for >11.3 h/week/year versus ≤2.4 h/week/year or by 11% for every 5 h/week/year spent in sedentary behavior. This study provides evidence for a decreased risk between lifetime physical activity and endometrial cancer risk and a possible increased risk associated with sedentary behavior

Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

BACKGROUND: Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. METHODS: Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. RESULTS: Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. CONCLUSION: Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

A randomised trial into the effect of an isolated hip abductor strengthening programme and a functional motor control programme on knee kinematics and hip muscle strength

Background: Dynamic knee valgus and internal femoral rotation are proposed to be contributory risk factors for patellofemoral pain and anterior cruciate ligament injuries. Multimodal interventions including hip abductor strengthening or functional motor control programmes have a positive impact of pain, however their effect on knee kinematics and muscle strength is less clear. The aim of this study was to examine the effect of isolated hip abductor strengthening and a functional motor control exercise on knee kinematics and hip abductor strength. Methods: This prospective, randomised, repeated measures design included 29 asymptomatic volunteers presenting with increase knee valgus and femoral internal rotation. Participants completed either isolated hip abductor strengthening or a functional motor control exercise for 5 weeks. Knee kinematics were measured using inertial sensors during 2 functional activities and hip abductor strength measured using a load cell during isometric hip abduction. Results: There were no significant differences in dynamic knee valgus and internal rotation following the isolated hip abductor or functional motor control intervention, and no significant differences between the groups for knee angles. Despite this, the actual magnitude of reduction in valgus was 10° and 5° for the functional motor control group and strengthening group respectively. The actual magnitude of reduction in internal rotation was 9° and 18° for the functional motor control group and strengthening group respectively. Therefore there was a tendency towards clinically significant improvements in knee kinematics in both exercise groups. A statistically significant improvement in hip abductor strength was evident for the functional motor control group (27% increase; p = 0.008) and strengthening group (35% increase; p = 0.009) with no significant difference between the groups being identified (p = 0.475). Conclusions: Isolated hip strengthening and functional motor control exercises resulted in non-statistically significant changes in knee kinematics, however there was a clear trend towards clinically meaningful reductions in valgus and internal rotation. Both groups demonstrated similar significant gains in hip abductor strength suggesting\ud either approach could be used to strengthen the hip abductors