An exploration into the sleep of workers on block-calving, pasture-based dairy farms.

The benefits of sufficient and high-quality sleep for people are well documented. Insufficient sleep increases the risk of accidents, injuries, and negative health implications for people. This is especially relevant for farmers, as they work with large animals and machinery. Dairy farming often requires early start times and long days, particularly over the high workload calving period in block calving, pasture-based systems. However, there is little published data quantifying the sleep quantity and quality of farmers over this period. In this study, the sleep patterns of workers (n = 33) on 10 New Zealand dairy farms was measured for 90 d over the spring calving period using a sleep measuring device (OuraTM ring, Oura Health Ltd., Oulu, Finland). Total sleep time (TST) averaged 6 h 15 min, lower than the required 7 to 9 h for optimal wellbeing and cognitive functioning. TST decreased over the calving period and was significantly correlated with both sleep start and wake times. Factors such as work start time, farm location, and role on farm influenced sleep quantity and quality; indicating adjusting these on-farm factors could positively impact TST. Further research is required to better understand sleep and its effect on dairy farmers, over both the calving period and the remaining months of the year.

Effect of altering milking interval when milking 3 times in 2 days on milk and component yields in pasture-based dairy systems.

Dairy farmers face challenges attracting and retaining staff, partly due to the difficulty meeting the desires of the modern workforce. These include flexible work hours and regular time off. The task of milking fundamentally affects the ability of dairy farmers to meet these desires. Milking contributes to a large proportion of the hours spent working on dairy farms. The number of milkings (milking frequency) and their timing (milking interval) within a day influence the number of hours spent milking and what time in the day they occur. Milking 3 times in 2 d (3-in-2) reduces the amount of time spent milking compared with milking twice a day (TAD), without reducing milk yield as much as milking once a day (OAD). However, long intervals between 3-in-2 milkings can still lead to a long workday if farmers are expected to work between milkings. The objective of this study was to determine the effect of milking interval within a 3-in-2 milking frequency on milk yield and composition at 2 stages of lactation and compare these with OAD and TAD milking. Cows (n = 200) were milked in 5 groups of 40 at 3 intervals of 3-in-2: 8-20-20 h, 10-19-19 h, and 12-18-18 h, along with 24 h (OAD), and 10 and 14 h (TAD), for 6 wk at early lactation (mean 24 d in milk ± 7 d, SD) and again at mid lactation (mean 136 d in milk ± 18 d). Milk yields were recorded at each milking and milk samples collected weekly to determine composition. At both early and mid lactation there were no significant differences in milk, fat, protein, or lactose yields between the three 3-in-2 intervals. Cows milked 3-in-2 produced 8% less milk than cows milked TAD and 14% more than cows milked OAD, with smaller differences observed at mid lactation between TAD and 3-in-2. For a 3-in-2 milking frequency, a shorter milking interval can be implemented on the days when cows are milked twice. This may allow farmers to shorten the working day when using 3-in-2, without compromising milk or component yields.

Reducing milking frequency from twice each day to three times each two days affected protein but not fat yield in a pasture-based dairy system.

Milking 3 times in 2 d (3-in-2) could enhance the attractiveness of the dairy workplace relative to twice-a-day milking (TAD) by reducing labor requirements for milking and increasing workforce flexibility. The objective of this study was to quantify the farm system interactions associated with milking 3-in-2 at 3 stages of lactation, with the aim of providing guidance to pasture-based dairy farmers and advisors on the likely consequences of adopting 3-in-2 milking on farm productivity and business performance. Seventy-nine multiparous and 37 primiparous cows were randomly allocated to 4 experimental farms stocked at 3.5 cows/ha. One herd was milked TAD for the whole lactation (August 2019 to May 2020), with the remaining 3 milked 3-in-2 for either the whole lactation, after December 1 when cows were an average of 101 d in milk, or after March 1 when days in milk averaged 189 d. Milking intervals over 48 h were 10-14-10-14 h for TAD and 12-18-18 h for 3-in-2. Animal, pasture, and farm system data were analyzed by linear regression, with the dependent variable being the annualized value of the performance metric of interest, and the number of days in the lactation milked 3-in-2 as the independent variable. For the proportion of the season milked 3-in-2, there was a significant effect on milk (-11%), protein (-8%), and lactose (-12%) yield per cow per year, but no effect of fat. Additionally, there was a positive effect (+6%) on body condition score before dry-off and the energy required for liveweight change (+26%), and a negative effect on the energy required for walking (-30%). There were no differences in estimated feed eaten, or pasture herbage accumulation, composition, or quality. Therefore, pasture management and feed allocation under 3-in-2 should be similar to TAD. On commercial farms, the degree to which reduced milk income can be offset by lower costs will be highly farm-specific, but opportunities for savings were identified in the results. The short walking distances on the research farm and potential to improve farm management using the time saved from fewer milkings suggests better production may be achieved with 3-in-2 milking on a commercial farm.

Improving parlor efficiency in block calving pasture-based dairy systems through the application of a fixed milking time determined by daily milk yield and milking frequency.

Adjusting end-of-milking criteria, in particular applying a maximum milking time determined by expected milk yield at an individual milking session, is one strategy to optimize parlor efficiency. However, this strategy can be difficult to apply practically on farm due to large differences in session milk yield, driven by milking interval, which affects milking routines and can be limited by in-parlor technology. The objective of this study was to test the hypothesis that a single fixed milking time (duration) could be applied at all milking sessions without compromising milk production or udder health for a range of milking intervals. To test the hypothesis, 4 experimental herds were established: (1) herd milked twice a day (TAD) using a 10- and 14-h interval, (2) herd milked TAD using an 8- and 16-h interval, (3) herd milked 3 times in 2 d using a 10-19-19-h interval, and (4) herd milked once a day (OAD). Herds consisted of 40 cows each, and were established for two 6-wk experimental periods, one in peak lactation and the other in mid-late lactation. Within each herd, half the cows had an end-of-milking criterion of 0.35 kg/min (Flow), and the other half had milking ended after a fixed period of time (FixedT) based on the average milking session yield, the daily milk yield divided by average number of milkings per day, irrespective of milking interval. We found no differences in daily milk yield between end-of-milking criteria due to residual milk from one milking likely increasing the proportion of milk in the udder cistern at the next milking session for the FixedT treatment. However, fat yield was compromised when the percentage of the herd with a truncated milking exceeded an estimated 33% at a milking session, which occurred in the TAD 8-16 herd due to the divergence from the average milking interval (in the case of TAD, 12-12 h). Applying a fixed milking time had no detrimental effects on udder health, except in the OAD herd in mid-late lactation, which had both a higher cell count and new intramammary infection rate. This warrants further investigation, although the majority of cultured bacteria were coagulase-negative staphylococci (CNS). Consequently, we conclude that, in general, with appropriate monitoring (e.g., weekly inspection) to ensure the proportion of the herd with truncated milkings does not exceed 33%, farmers in pasture-based dairy systems can use a fixed milking time to improve parlor efficiency.

Opportunities for improving the safety of dairy parlor workers.

One aspect of a successful dairy business is attracting and retaining skilled staff. The ability to do this is influenced by workplace attractiveness, one aspect of which is worker comfort and safety. Working with heavy machinery and animals makes dairy farming a dangerous occupation relative to many other sectors. Milking is the most time-consuming task on pasture-based dairy farms, and the parlor is the logical site of a number of injuries, although little is known about their causes or their relationship to parlor design and management. To investigate worker safety further, we conducted an on-farm survey on New Zealand dairy farms between December 2018 and March 2019. The survey had 3 objectives: to identify common causes of injuries relating to milking; to describe variations in milking parlor design and management practices on dairy farms; and to identify management and parlor factors that contribute to milking injuries. Analysis of accident compensation data from the state-run accident insurer for a 5-yr period from July 2013 to June 2018 was a fourth objective. Accident claims identified as related to milking through a key word search averaged NZ$252 (NZ$1 was equivalent to US$0.60 on May 19, 2020) per claim for non-severe injuries and NZ$9,334 per claim for severe injuries, for a total of NZ$1.95 million per year. A total of 136 injuries were reported on 99 of the 560 farms surveyed, and accident insurance claims were made for 53 of these injuries. The survey found that 48% of injuries occurred while workers were attaching clusters: typically soft-tissue and fracture injuries to fingers, hands, wrists, and arms. Injuries to these body parts represented the greatest cost (51% of the annual insurance cost) and identified safe cluster attachment as an area of focus for reducing milking injuries. Potential low-cost solutions include improved cluster design and a hand-arm guard. We identified a clear seasonal trend that coincided with busy periods in a seasonal block calving system, suggesting that options to reduce fatigue in spring may be beneficial; however, the number of hours worked or number of consecutive days worked were not associated with the number of milking injuries. Those aged 20-29 yr had more injuries relative to their proportion of the workforce, indicating that more training may be beneficial (e.g., setting ergonomic milking routines). Female workers were at greater risk of injury than males; this finding may have been related to the height of the animal relative to the height of the milker.

Analysis of adoption trends of in-parlor technologies over a 10-year period for labor saving and data capture on pasture-based dairy farms.

The use of precision technology is increasingly seen as an option to improve productivity, animal welfare, resource use efficiency, and workplace features on dairy farms. There is limited research related to longitudinal adoption patterns of precision dairy technologies and reasons for any patterns. The aim of this analysis was to investigate trends in technology adoption regarding both the amount (number of farms with a technology) and intensity (number of technologies per farm) of adoption. Surveys of parlor technology adoption were conducted on New Zealand dairy farms in 2008, 2013, and 2018, with 532, 500, and 500 respondents, respectively. Technologies were grouped into labor-saving (LS, such as automatic cluster removers) or data-capture (DC, such as in-line milk meters) categories. Trends were examined for farms that had only LS, only DC, or LS+DC technologies. Technology adoption increased over time; the likelihood of technology adoption in 2018 (and 2013 in parentheses) increased by 21 (22), 7 (68), and 378% (165) for LS, DC, and LS+DC technology groups, respectively, compared to 2008. Farms with LS+DC technologies also had a greater proportion of LS technologies compared to non-LS+DC farms, although this relationship declined over the 10-yr period. The use of a rotary versus herringbone parlor was estimated to be associated with 356 and 470% increase in the likelihood of adopting LS technologies and LS+DC, respectively, from 2008 to 2018. Regional differences in adoption were also found, with the likelihood of adopting DC and LS+DC technologies found to be 46 and 59% greater, respectively, in the South Island of New Zealand, compared to the base region of Waikato. The results highlight the importance of understanding spatial and temporal farm characteristics when considering future effect and adoption of precision dairy technologies. For example, the analysis indicates the occurrence of 2 trajectories to technology investment on farms, where larger farms are able to take advantage of technology opportunities, but smaller farms may be constrained by factors such as lack of economies of scale, limited capital to invest, and inability to retrofit technology into aging parlor infrastructure.

Short communication: Technologies and milking practices that reduce hours of work and increase flexibility through milking efficiency in pasture-based dairy farm systems.

To attract and retain quality employees, dairy farms must be competitive with other workplaces offering more conventional hours of work. Milking requires significant labor input and influences the start and end times of the working day, affecting flexibility to suit employee needs or availability. The use of labor-saving technology and milking management strategies could help with this challenge. Previous studies have used scenario modeling in attempt to quantify the value of in-parlor technologies, however, they have relied on assumptions about the effect of the technologies on labor in the dairy. Similarly, the effect of management strategies on work patterns, such as flexible milking intervals (changing the timing of milking), has not been evaluated. The aims of this study were to (1) quantify the milking labor requirements in a range of pasture-based dairy farm systems and (2) identify practices or technologies that facilitate efficient milking. A telephone survey of 500 dairy farmers in New Zealand was conducted during April and May 2018, with questions asked about milking practices and technology use. Predictive analysis showed that at peak lactation, milking required between 17 and 24 h/wk per worker for farms milking twice a day, representing 43 to 58% of a conventional 40-h work week, depending on parlor type (herringbone or rotary), the number of clusters, and herd size. Using milking intervals of 8 and 16 h (intervals between milkings), compared with the more usual 10 and 14 h, largely avoided starting milking before 0500 h. Eight percent of herds were milked once a day, which required between 7 and 14 h/wk per worker (18-35% of a 40-h week). ANOVA showed that for metrics that related to people (labor efficiency and work routine), using automatic teat spraying had a positive effect on efficiency. Having both automatic cluster removers and drafting were associated with longer milking times in terms of throughput and row/rotation time compared with using drafting only. The results highlight considerable opportunity to reduce the number of hours those milking (employers and employees) spend in the parlor and increase staff time flexibility through milking (e.g., intervals between milkings) and parlor management (e.g., row/rotation time) and use of specific technologies. This study provides useful data for those wishing to analyze the likely value of an in-parlor automation technology or management practice for an individual situation.

Short communication: Milk fat payment affects the relative profitability of Jersey and Holstein-Friesian cows at optimal comparative stocking rate.

Choice of stocking rate and breed of cow are 2 strategic decisions that affect the profitability of pasture-based dairy farm businesses. This study sought to analyze the effects of a range of fat and protein prices on the profitability of the Jersey (J) and Holstein-Friesian (HF) breeds at 2 comparative stocking rates (CSR): 80 kg of body weight (BW) per tonne of dry matter (DM) of feed (CSR80), and 100 kg of BW per tonne of DM of feed (CSR100). Data were obtained from a recently published study, and equations constructed to determine the values for fat and protein at which each breed broke even (profit = NZ$0/ha; at time of writing, NZ$1 = US$0.69 or €0.60), returned equal profit, and exceeded the other breed by 1% or 5%. At CSR100 there were few combinations of fat and protein prices for which HF were more profitable than J. At CSR80, J and HF were equally profitable at a fat price of NZ$5.67 ± NZ$0.20 per kilogram, depending on protein price. The study also highlighted the importance of including volume adjustments in milk price calculations when differences in milk composition exist, as the fat price at which the profitability of HF and J were equal was NZ$1.23/kg lower when volume adjustments were included. The recent increase in the value of fat relative to protein favors J. Farmers should consider the medium- to long-term outlook of fat price when evaluating breed choice for their farm system.

Analysis of milking characteristics in New Zealand dairy cows.

The objective of this study was to describe the variation in milking characteristics, and factors associated with these traits, in grazing dairy cows milked without premilking stimulation. Milk yield, duration, and average and maximum milk flow rate data were collected from 38 farms in New Zealand at 2 time points (spring and autumn) during the 2010 to 2011 season. Subsequently, a second data set, allowing the generation of daily milk flow profiles, was collected from 2 farms in the 2011 to 2012 season. Corresponding animal data, such as breed, date of birth, and ancestry information, were extracted from the New Zealand Dairy Industry Good Animal Database (New Zealand Animal Evaluation Ltd., Hamilton, New Zealand). Residual milking duration (deviation from the regression line of milk yield on milking duration) was calculated, allowing the identification of fast-milking cows independent of milk yield. Variance components for the milking characteristics traits were estimated using an animal linear mixed model. The average milk yield was 10 kg/milking and the average milking duration was 360 s. The average milk flow rate was 1.8 kg/min and maximum milk flow 3.3 kg/min, with 44% of milk flow curves being classified as bimodal. Primiparous animals exhibited different milk flow profiles, with a lower maximum flow, than multiparous animals, possibly due to differences in cisternal capacity. Residual milking duration was shortest (-10s) in mid-lactation (121-180 d) and was 13s longer for Jersey compared with Friesian cows; however, it was 19s shorter when adjusted for energy content. Residual milking duration had a negligible genetic correlation (-0.07) with milk yield, indicating that selection for cows with shorter residual milking duration should have a negligible effect on milk yield. A heritability of 0.27 indicated that residual milking duration could be valuable as part of a breeding program. Knowledge of the distribution of milking durations for a given milk yield allows farmers to choose appropriate cluster-on time when using a maximum milking time strategy to improve milking efficiency.

Grazing behavior of dairy cows under contrasting pasture allocation frequencies and areas.

This study aimed to compare grazing behavior of dairy cows with highly contrasting pasture allocation frequencies. The study ran from September 9, 2022, to December 2, 2022 (12 wk), during a time when daily pasture growth was expected to exceed daily herd intake. Three pasture allocation frequencies were compared, each with 11 spring-calving cows grazing a 4-ha farmlet. The allocations were high frequency rotational grazing (HFRG; 32.5 m2/cow per allocation and 4 allocations/d), rotational grazing with weekly allocations (7RG; 909 m2/cow per allocation and each allocated area continuously grazed over 7 d), and continuous grazing (CG; 1,818 m2/cow per allocation). Animal behavior was monitored using IceQube accelerometers (Peacock Technology) and CowManager ear tags (Agis Automatisering BV). Milk yield and composition were measured and pasture cover was estimated. Daily eating time was highest for CG animals, whereas lying time, lying bouts, and ruminating time were lowest, with no differences between HFRG and 7RG. There were no differences in fat- and protein-corrected milk yield between farmlets; however, estimated accumulated pasture yield was greater with more frequent allocations. Although milk production did not differ between treatment groups, this appeared to be achieved through greater eating times when allocated pasture less frequently, at the expense of time spent lying.

Identifying and predicting heat stress events for grazing dairy cows using rumen temperature boluses.

Heat stress events in dairy cows are associated with behavioral and physiological changes such as seeking shade, increased respiration rate and body temperature, reduced milk production, and psychological distress. Knowledge of the relationship between weather and animal responses to heat stress enables automated alerts using forecast weather, aiding early provision of shade or other mitigation practices. While numerous heat stress indices for cattle have been developed, these have limitations for cows exposed to wind and solar radiation (i.e., predominantly grazing outdoors or managed on pasture). To develop a predictive model for heat stress events in pasture-based dairy systems, rumen temperature data from smaXtec (smaXtec animal care GmbH, Graz, Austria) rumen boluses in 443 cows on 3 dairy farms in Northland, New Zealand, were used to identify heat stress events and these were matched with automated weather station data collected on or near the farm. Heat stress rate (HSR) was defined as the percentage of cows within an age-breed group having a rumen temperature greater than 3 standard deviations above an individual cow's mean and heat stress events were defined as HSR >25%. Single and multiple linear regression models, including published heat stress indices, were generally able to predict a high proportion of heat stress events (sensitivity 34%-68%), but were insufficiently discriminating, predicting also a high number of false positives (precision only 9%-27%). A machine learning algorithm, cubist, was the best performing model, predicting 79% of heat stress events with a precision of 52% for this dataset. Our proof-of-concept study demonstrates the potential of this approach, using climate data to predict and forecast heat stress events in pasture-based dairy systems. Further work should test the cubist model using independent data, refine dataset construction, investigate the value of including known animal variables such as cow age or breed, and incorporate other measures of heat stress such as respiration rate.

Milking efficiency for grazing dairy cows can be improved by increasing automatic cluster remover thresholds without applying premilking stimulation.

It was hypothesized that streamlined premilking stimulation routines are effective at reducing cow cluster-on time but are not required to maintain milk yield or quality when increasing the automatic cluster remover (ACR) threshold above 0.4 kg/min. This was tested by examining the effect of 3 premilking treatments and 4 ACR thresholds over an 11-wk period with 96 mixed-age New Zealand Friesian-Jersey cross cows during peak lactation. Three premilking treatments were chosen: attach cluster immediately (control), attach cluster immediately and apply 30s of mechanical stimulation (Stim), and remove 2 squirts of milk from each quarter and attach cluster (Strip). Four ACR milk flow rate thresholds were imposed: 0.2 kg/min (ACR2), 0.4 kg/min (ACR4), 0.6 kg/min (ACR6), and 0.8 kg/min (ACR8). Measurements included individual cow milk yield, cluster-on time, average milk flow rate, maximum milk flow rate, time to average milk flow rate, time from maximum milk flow rate to end of milking, and the milk flow rate and cumulative yield at predetermined intervals during each milking session. Milk composition and somatic cell count (SCC) were determined on composite milk samples, collected weekly. Postmilking strip yield was measured at the end of each treatment period. Cows receiving the Strip treatment had a 3 to 4% shorter cluster-on time than did cows on the control treatment, but cows receiving Stim were not different from the control cows. Milk yield, SCC, and postmilking strip yield were not different between the 3 premilking treatments. Cluster-on time of the ACR8 cows was 18 to 26% less than that of the ACR2 cows, but SCC and milk production variables did not differ between the 4 end-of-milking treatments, despite higher strip yields as the ACR threshold increased. Increasing the ACR threshold is an effective strategy to improve milking efficiency (cows milked per operator per hour) in situations where the work routine times of dairy operators can be accelerated. To achieve the greatest milking efficiency, clusters should be attached immediately without premilking manual or mechanical stimulation.

Short-term application of prestimulation and increased automatic cluster remover threshold affect milking characteristics of grazing dairy cows in late lactation.

It was hypothesized that reducing cow cluster-on time by increasing automatic cluster remover (ACR) thresholds above 0.4 kg/min would require premilking stimulation of the mammary gland to maintain milk yield. This was tested by examining the interaction between 4 ACR thresholds and 3 premilking treatments over an 8-wk period with 96 mixed-age Friesian-Jersey cross cows being milked twice per day in late lactation (average production: 13.9 kg/d). The 3 premilking treatments were attach cluster immediately (control), attach cluster 60s after entering the dairy (delay), or remove 2 squirts of foremilk from each quarter and attach cluster 60s after entering the dairy (Prep). Four ACR thresholds were chosen, where the cluster was removed after the milk flow rate was less than 0.2 (ACR2), 0.4 (ACR4), 0.6 (ACR6), and 0.8 kg/min (ACR8). Measurements included individual cow milk yield, cluster-on time, average milk flow rate, maximum milk flow rate, time from cluster attachment to average milk flow rate, milk yield in the first 2 min, time from maximum milk flow rate to end of milking, and the milk flow rate at predetermined intervals during each milking session. Composite milk samples were collected weekly at a.m. and p.m. milkings to determine composition and somatic cell count (SCC). On 3 occasions during the experiment, postmilking strip yield was measured. No interactions were detected between premilking treatment and ACR threshold in any of the measured variables. Cows receiving the Prep treatment had a 5 to 9% shorter cluster-on time than the control treatment. Milk yield, SCC, postmilking strip yield, and maximum flow rate were not different between the 3 premilking treatments. Cluster-on time of the ACR8 cows was 21 to 29% less than ACR2, but SCC and milk production variables were not different between the 4 end-of-milking treatments despite higher strip yields as ACR threshold increased. Increasing ACR threshold offers the potential to reduce the duration of milking without detriment to overall productivity. The results of the premilking treatments indicate that to achieve the most efficient routine, the operator should attach clusters as close as possible to the first bail in rotary dairies to increase bail utilization in pasture-based systems. If cluster attachment can be sped up and ACR threshold lifted, significant potential exists to decrease herd milking duration and improve labor productivity.

Effect of fat and CHO meals on intermittent exercise in soccer players.

Pre-exercise meals containing carbohydrates (CHO) are recommended to athletes, although there is evidence to suggest that a high fat meal prior to exercise increases utilisation of fats yet may not adversely affect performance. This study investigated the effect of a high fat and high CHO pre-exercise meal prior to high intensity intermittent exercise. Ten male recreational soccer players performed a soccer specific protocol followed by a 1 km time trial 3 ½ h after ingesting one of 2 test meals, high fat meal (HFM) or a high CHO meal (HCM). Blood glucose, fatty acids (FA), glycerol, ß-hydroxybutyrate, lactate and insulin were assessed prior to the meal, pre-exercise, half-time, and post-exercise, whilst rates of CHO and fat oxidation were determined at 4 time points during the exercise as well as heart rate (HR) and rating of perceived exertion (RPE). Significant increases in FA, glycerol, ß-hydroxybutyrate and fat oxidation after the HFM were observed, while CHO oxidation was significantly higher following the HCM (P<0.05). No performance effect was found for the 1 km time trial (HFM: 228.6+14.4 s; HCM: 229.4+26.5 s) (mean+SD). These findings suggest that the type of meal ingested prior to soccer simulated exercise has an impact on metabolism, but not on the subsequent performance as determined in the present study.

Responsible robotics design-A systems approach to developing design guides for robotics in pasture-grazed dairy farming.

Application of robotics and automation in pasture-grazed agriculture is in an emergent phase. Technology developers face significant challenges due to aspects such as the complex and dynamic nature of biological systems, relative cost of technology versus farm labor costs, and specific market characteristics in agriculture. Overlaying this are socio-ethical issues around technology development, and aspects of responsible research and innovation. There are numerous examples of technology being developed but not adopted in pasture-grazed farming, despite the potential benefits to farmers and/or society, highlighting a disconnect in the innovation system. In this perspective paper, we propose a "responsibility by design" approach to robotics and automation innovation, using development of batch robotic milking in pasture-grazed dairy farming as a case study. The framework we develop is used to highlight the wider considerations that technology developers and policy makers need to consider when envisaging future innovation trajectories for robotics in smart farming. These considerations include the impact on work design, worker well-being and safety, changes to farming systems, and the influences of market and regulatory constraints.

Review: Anticipating alternative trajectories for responsible Agriculture 4.0 innovation in livestock systems.

Technological change has been a constant feature of livestock systems leading to the third agricultural 'green' revolution of the mid-20th century. Digital technologies are now leading us into the fourth agricultural revolution, where sustainable food production is supported by technologies that collect data useful for farm and supply chain performance improvement, along with task automation and compliance. However, the potential benefits of digital agricultural futures are uncertain and plagued by unrealized expectations of previous innovations. The aims of this paper are to articulate current trends in technology and livestock systems and anticipate future trajectories for Agriculture 4.0 in relation to meeting sustainability and animal welfare outcomes for livestock systems. We use a 'Futures Triangle' approach to review the role of technology in livestock systems. The main findings are that previous work envisioning technological livestock futures have favoured pull of the future factors (techno-optimists) or weight of the past (techno-pessimists), rather than a balance of pull, push and weighting factors. Responsible Agriculture 4.0 innovation requires public-private collaboration of innovation system stakeholders, including policy makers, farmers, consumers, as well as technology developers, to enable development of transition pathways from a systems perspective. The use of responsible innovation processes, including anticipation on alternative futures, should also be built into innovation processes to support critical reflection on technological trajectories and related innovation system consequences, both desirable and undesirable.

Hydrolase activity in the venom of the pupal endoparasitic wasp, Pimpla hypochondriaca.

Venom from the pupal endoparasitoid, Pimpla hypochondriaca has previously been shown to contain a mixture of biologically active molecules. Currently, P. hypochondriaca venom was examined for the presence of hydrolase activity. Six hydrolases were consistently detected using the API ZYM semiquantitative colourimetric kit. The main hydrolases detected were; acid phosphatase, beta-glucosidase, esterase, beta-galactosidase, esterase lipase, and lipase. The most rapid and intense colour reaction was detected for acid phosphatase. The pH optimum and the specific activity of venom acid phosphatase was determined using p-nitrophenol phosphate as a substrate and were 4.8 and 0.47 nmol p-nitrophenol/min/microg of venom protein, respectively. The acid phosphatase activity was inhibited in a dose dependent manner by sodium fluoride (IC(50) 4.2 x 10(-4) M), and by cocktail inhibitor 2 (CI 2). P. hypochondriaca venom has previously been shown to display potent cytotoxic activity towards Lacanobia oleracea haemocytes maintained in vitro. The contribution of acid phosphatase in venom to this cytotoxic activity was investigated by titrating venom against CI 2 prior to the addition of L. oleracea haemocytes. The results suggest that, despite the relatively high levels of acid phosphatase activity in venom, venom acid phosphatase plays no role in the antihaemocytic activity of P. hypochondriaca venom in vitro.

5-Aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines as potent, orally active, nonsteroidal progesterone receptor agonists: the effect of D-ring substituents.

Several 5-(4-chlorophenyl)-1,2-dihydro-5H-chromeno[3,4-f]quinolines were prepared to determine the effects of substitution at C(8) and C(9) on the progestational activity of this pharmacophore. In combination with a halogen (F or Cl) at C(9), replacement of the C(5) aryl group with variously substituted aryl groups resulted in optimization of the progestational activity, affording compounds with in vitro activity greater than that of progesterone as measured by a cotransfection assay using human progesterone receptor subtype-B (hPR-B). Binding affinities (Ki) to hPR-A were subnanomolar in many cases. These in vitro effects were verified in vivo using a rodent model. Compound 10 (LG120794, 9-chloro-5-(4-chlorophenyl)-1,2-dihydro-2,2,4-trimethyl-5H-chromeno++ +[3,4-f] quinoline) was more potent than medroxyprogesterone acetate at counterpoising the effects of estradiol benzoate in the uterine wet weight assay using immature rats.

Discovery and preliminary SAR studies of a novel, nonsteroidal progesterone receptor antagonist pharmacophore.

A series of 6-aryl-1,2-dihydro-2,2,4-trimethylquinolines was synthesized and tested for functional activity on the human progesterone receptor isoform B (hPR-B) in mammalian (CV-1) cells. The lead compound LG001447 (1,2-dihydro-2,2, 4-trimethyl-6-phenylquinoline) was discovered via directed high throughput screening of a defined chemical library utilizing an hPR-B cotransfection assay. Electron-withdrawing substituents at the meta position of the C(6) aryl group afforded substantial improvements in hPR modulatory activity. Several analogues were able to potently block the effects of progesterone in vitro. Two compounds, 10 (LG120753) and 11 (LG120830) with potencies comparable or equal to the steroidal hPR antagonist onapristone (ZK98,299), were demonstrated to act as antiprogestins in vivo after oral administration to rodents. This is the first disclosure of orally active nonsteroidal antiprogestins.

Synthesis and biological activity of a novel series of nonsteroidal, peripherally selective androgen receptor antagonists derived from 1,2-dihydropyridono[5,6-g]quinolines.

A new nonsteroidal antiandrogenic pharmacophore has been discovered using cell-based cotransfection assays with human androgen receptor (hAR). This series of AR antagonists is structurally characterized by a linear tricyclic 1,2-dihydropyridono[5,6-g]quinoline core. Analogues inhibit AR-mediated reporter gene expression and bind to AR as potently as or better than any known AR antagonists. Several analogues also showed excellent in vivo activity in classic rodent models of AR antagonism, inhibiting growth of rat ventral prostate and seminal vesicles, without accompanying increases in serum gonadotropin and testosterone levels, as is seen with other AR antagonists. Investigations of structure-activity relationships surrounding this pharmacophore resulted in molecules with complete specificity for AR, antagonist activity on an AR mutant commonly observed in prostate cancer patients, and improved in vivo efficacy. Molecules based on this series of compounds have the potential to provide unique and effective clinical opportunities for treatment of prostate cancer and other androgen-dependent diseases.