OBJECTIVES/GOALS: Adolescence represents a critical period for substance use initiation. Various factors may contribute to trying a sip or single puff of a substance, that could lead to more frequent use. However, less is known about how predictors from multiple domains converge to impact risk for general substance use initiation. METHODS/STUDY POPULATION: The Adolescent Brain Cognitive Development (ABCD) study is a multi-site longitudinal study following youth into early adulthood. The present study included 7,644 ABCD children who reported no lifetime substance use (including any experimentation) at baseline (ages 9–10). Our primary aim was to use a random forest classification model to predict binary substance use initiation, defined as trying any non-prescribed substance (e.g., alcohol, tobacco, cannabis, non-prescribed medications), during a 2-year follow-up after baseline. A total of 402 variables from the following categories were examined as predictors: demographics, peer substance use and availability, mental and physical health, culture and environment, biospecimens, neurocognitive functioning, and structural neuroimaging variables. RESULTS/ANTICIPATED RESULTS: Over a two-year follow-up, 751 (9.8%) of substance-naïve children reported trying a substance by age 11. The most common substance was alcohol, followed by cannabis and tobacco. Mean Decrease Accuracy (MDA) values were used to assess the relative importance of each predictor. The overall accuracy of the model in accurately predicting group membership (no substance use initiation vs. substance use initiation) was 57.66%. Of the top 5 predictors, the most important predictor was intent to use alcohol (MDA = .002). The following top predictors were structural neuroimaging variables: volume and surface area of right lateral occipital lobe (MDA = .0009 and .0008, respectively), surface area of right inferior temporal lobe (MDA = .0007), and surface area of left superior frontal lobe (MDA = .0007). DISCUSSION/SIGNIFICANCE: A combination of intent to use alcohol and structural neuroimaging indices were among the top predictors of substance use initiation. Understanding predictors of early substance use experimentation is important for identifying at-risk youth that may require targeted intervention approaches.

The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.

We present the development and characterization of a high-stability, multi-material, multi-thickness tape-drive target for laser-driven acceleration at repetition rates of up to 100 Hz. The tape surface position was measured to be stable on the sub-micrometre scale, compatible with the high-numerical aperture focusing geometries required to achieve relativistic intensity interactions with the pulse energy available in current multi-Hz and near-future higher repetition-rate lasers ( $>$ kHz). Long-term drift was characterized at 100 Hz demonstrating suitability for operation over extended periods. The target was continuously operated at up to 5 Hz in a recent experiment for 70,000 shots without intervention by the experimental team, with the exception of tape replacement, producing the largest data-set of relativistically intense laser–solid foil measurements to date. This tape drive provides robust targetry for the generation and study of high-repetition-rate ion beams using next-generation high-power laser systems, also enabling wider applications of laser-driven proton sources.

A series of measures of calf welfare was developed through a process of expert consultation. A welfare assessment of group-housed calves was carried out on 53 UK dairy farms during the winter of 2000/01. The assessment used animal-based measures including direct observation of the calves and examination of their health history through a review of farm records. The findings from this were compiled into a profile of calf welfare which outlined the range of results for each measure used. The results fell into the three categories of respiratory health, nutrition and general appearance. A broad range of results was found across the farms visited for the measures in each of these categories. Some farms performed well for all measures taken, and no farms performed consistently badly across all aspects of calf welfare. The majority of farms combined aspects of both good and poor welfare performance.

The within-farm prevalence of vulva biting in breeding sows in south-west England was investigated using a postal survey sent to 410 pig farmers in January 1997. The response rate was 65 per cent and there were 83 useable replies. The majority of farms where vulva biting was reported indicated a low within-farm prevalence of 1-9 per cent of sows affected, although prevalences as high as 30-60 per cent were reported. The injuries reported ranged from bleeding to removal of the whole vulva, the most commonly reported injuries being bleeding and superficial damage to the vulva. No long-term effects from this injury to service and dry sows were reported by 70 per cent and 76 per cent of farmers respectively. Competition for food, aggressive sows, closeness to farrowing and mixing of sows were the most common reasons suggested by these farmers as causes of vulva biting.

This paper describes an approach to assessing the overall welfare of cows on dairy farms. Veterinary and behaviour experts were shown results for ten selected welfare parameters for 25 pairs of dairy farms paired for farm assurance status but with similar geographical location and husbandry system. From this information alone they were asked to state which farms had better welfare. Overall, there were no significant differences between the conclusions of veterinary and behaviour experts. There was a significant relationship between the proportion of experts rating a farm as poorer and the measured difference in the number of cows with lameness or rising restrictions between the paired farms. There were no significant relationships between the expert decisions and differences in milk yield, flight distance, swollen hocks, mastitis incidence, dystocia level, conception rates, prevalence of thin cows and proportion of cows with dirty udders. Clearly, experts rate lameness and discomfort as highly important indices of poor welfare in dairy cows.

A Delphi technique was used to gather the opinions of animal welfare experts on the most appropriate measures for welfare assessment of farm animals. The experts were asked to consider measures that were directed towards the animal (animal-based), rather than measurement of their environment. This systematic approach was designed to achieve a degree of consensus of opinion between a large number of experts. Two rounds of postal questionnaires were targeted at people with expertise in one or more of the species of interest. The respondents suggested measures based upon observations of health status, behaviour, and examination of records. These measures reflect the animal's welfare state — in other words, how the animal is coping within the environment and husbandry system in which it lives. The measures for cattle, pigs and laying hens were categorised into 22, 23 and 28 aspects, respectively, with the highest ranking of importance being given to observation of lameness in dairy cattle and pigs and to observation of feather condition in laying hens. This Delphi study was the basis for the development of a series of protocols to assess the welfare state of dairy cattle, pigs and laying hens.

The Welfare of Farmed Animals (England) Regulations (2007) make it an offence to allow unnecessary suffering to animals, highlighting that farmers have a duty of care for their livestock. Despite this, the current global mean prevalence of lameness in sheep in England is 5%; ie ~750,000 lame adult sheep at any time. To investigate farmers’ attitudes to sanctions and rewards as drivers to reduce the prevalence of lameness in sheep, farmers’ attitudes to external inspections, acceptable prevalence of lameness and attitudes on outcomes from inspections were investigated using a self-administered questionnaire. A total of 43/102 convenience-selected English sheep farmers responded to the questionnaire. Their median flock size was 500 ewes with a geometric mean prevalence of lameness of 2.8%. Few farmers selected correct descriptions of the legislation for treatment and transport of lame sheep. Participants considered 5-7.5% prevalence of lameness acceptable and were least tolerant of farmers who rarely treated lameness and most tolerant of farmers experiencing an incident out of their control, eg disease outbreak. Participants consider sanctions and rewards would help to control lameness on sheep farms in England. Sanctions (prosecution, reduction in payment from the single [basic] payment scheme or suspension from a farm assurance scheme) were considered ‘fair’ when lameness was ≥ 10% and rewards ‘fair’ when lameness was ≤ 2%. If these farmers’ attitudes are applied to 1,300 randomly selected flocks with a mean prevalence of lameness of 3.5%, 24.6% of flocks that had ≥ 10% lameness would be sanctioned and 32.5% of flocks that had ≤ 2% lameness would be rewarded.

We investigated the temporal associations between the severity of foot lesions caused by footrot (FR) and the severity of lameness in sheep. Sixty sheep from one farm were monitored for five weeks. The locomotion of each sheep was scored once each week using a validated numerical rating scale of 0-6. All feet were then examined, FR was the only foot lesion observed; the severity of FR lesions was recorded on a scale from 0 to 4. Sheep had a locomotion score > 0 on 144/298 observations. FR lesions were present on at least one foot on 83% of observations of lame sheep but also present on 27% of observations where sheep were not lame; 95% of these sheep with a lesion but not lame had FR score 1. The results from a linear mixed model with locomotion score as the outcome were that the mean (95% CI) locomotion score of 0.28 (0.02, 0.53) in sheep with no lesions increased by 0.35 (0.05, 0.65) in sheep with FR score 1 or 2 and by 1.55 (1.13, 1.96) in sheep with FR score > 2 at the time of the observation; indicating that as the severity of the lesion increased, the severity of lameness increased. One week before an FR score > 2 was clinically apparent, sheep had a locomotion score 0.81 (0.37, 1.24) higher than sheep that did not have an FR score > 2 in the subsequent week. One week after treatment with intramuscular antibacterials the locomotion score of lame sheep reduced by 1.00 (0.50, 1.49). Our results indicate a positive association between severity of FR lesions and locomotion score and indicate that some non-lame and mildly lame sheep have footrot lesions. Treatment of even those mildly lame will facilitate healing and probably reduce the spread of infection to other sheep in the same group.

Breeding and housing wild animals in captive environments can pose challenges for their welfare. In South Africa, thousands of lions (Panthera leo) are bred and raised at commercial captive breeding facilities, so called ‘lion farms’, for use in tourism, trophy hunting and traditional medicine. To gain a better understanding of the potential welfare challenges faced by lions on farms we reviewed 91 peer-reviewed articles relating to lion welfare, identified via a systematic review of the scientific literature. Across these studies, we identified 170 different terms relating to negative behaviours and physical health afflictions. The majority of these terms were associated with disease and injury (124; 73%), followed by negative behaviours (19; 11%), negative mental experiences (15; 9%), nutritional concerns (7; 4%), and environmental challenges or discomfort arising from the animal's surroundings (5; 3%). Of the 91 articles, 32 (35%) focused on data concerning captive lions. Only two studies focused specifically on data obtained from lion farms in South Africa, whilst the remainder reported on data collected from zoos, wildlife parks, sanctuaries, game reserves and private ownership. Our preliminary review of the scientific literature draws attention to some of the challenges associated with caring for lions in captivity, and outlines the potential significance of these welfare challenges for commercial lion farms. Our data highlight the apparent lack of scientific research involving captive lion welfare generally, particularly data collected at commercial breeding facilities in South Africa and the consequences this could have for the welfare of thousands of lions within the industry.

Lameness is one of the greatest infringements of welfare in dairy cows. The objective of this study was to investigate associations between milk yield and foot lesions causing lameness in Chilean dairy cattle with the hypothesis that if we can demonstrate that lameness reduces yield, and so income, from lame dairy cows then we have both economic and welfare arguments for reducing lameness in dairy cattle. For one year, all lame cows from seven farms with Holstein Friesian cattle were treated by their herdsmen. Herdsmen were trained by the researcher and a colour atlas was utilised to assist in diagnosis of lesions. All abnormalities on the foot and the suspected cause of lameness were recorded, and cattle were treated. A two-level hierarchical model with repeated monthly test-day yields within cows was used to investigate the impact of double sole (DS), sole ulcer (SU), white line disease (WLD), digital dermatitis (DD) and all ‘other’ causes of lameness on milk yield before and after treatment. There were 1,635 cows with complete data. Cattle with a DS were higher yielding than cattle that were never lame with a reduction in yield from four months before treatment. Cattle lame with DD were higher yielding than non-lame cattle before and after treatment. For all causes of lameness, yield increased the month after treatment. We conclude that lesions causing lameness reduced the milk yield of dairy cows in these seven herds in Chile. We discuss the current evidence base for prevention of lameness in dairy cows and hypothesise that rapid treatment is a feasible current approach to improve cow welfare immediately and probably reduce milk lost; more evidence for effective prevention is required.

This review article summarises the evidence for an effective management protocol for footrot to sheep, the welfare and economic benefits of such a protocol and its likely uptake by farmers. Over 90% of lameness in sheep in England is caused by Dichelobacter nodosus, the aetiological agent of footrot. Farmers can recognise lame sheep both from video clips and when examining their own sheep but make a separate decision about whether to catch lame sheep. Only farmers who catch and treat mildly lame sheep immediately report a low prevalence of lameness (< 5%). From a within-farm clinical trial, treatment of sheep lame with footrot with parenteral antibiotic and topical spray led to over 90% recovery from lameness within 10 days whilst only 25% of sheep treated with foot trimming and topical spray recovered in 10 days. In parallel, a within-farm clinical trial with approximately 800 ewes was run for 18 months to test the hypothesis that rapid appropriate treatment led to reduced prevalence of lameness. Ewes were stratified and randomly allocated to one of two groups. The prevalence and incidence of lameness decreased in the treatment group, where lame sheep were treated with parenteral and topical antibacterials within three days of being observed lame, but remained at approximately 8% in the control group where lame sheep were treated with trimming hoof horn and topical antibacterial spray when the farm shepherd considered them sufficiently lame. Sheep in the treatment group had a higher body condition and produced more lambs that grew faster. The net economic benefit to all sheep (whether lame or not) in 2006 was £6 per ewe put to the ram. A group of 265 farmers were asked about their satisfaction with methods to manage footrot. Satisfied farmers reported a prevalence of lameness of ≤ 5% and used rapid individual treatment. Dissatisfied farmers reported a prevalence of lameness of > 5% and used whole-flock footbathing and vaccination. Overall, farmers stated that their ideal managements would be footbathing and vaccination. One explanation for this apparent inconsistency is that farmers want effective vaccines and footbaths; an alternative explanation is that this is an example of cognitive dissonance, where subjects adopt a belief because it is their current practice despite evidence that it is not effective. We conclude that farmers can identify lame sheep and that rapid treatment of individual sheep lame with footrot with intramuscular and topical antibacterials is currently the most effective control of interdigital dermatitis and footrot in sheep but that in future effective measures that prevent footrot would be ideal.

Gun ownership is a highly consequential political behavior. It often signifies a belief about the inadequacy of state-provided security and leads to membership in a powerful political constituency. As a result, it is important to understand why people buy guns and how shifting purchasing patterns affect the composition of the broader gun-owning community. We address these topics by exploring the dynamics of the gun-buying spike that took place during the COVID-19 pandemic, which was one of the largest in American history. We find that feelings of diffuse threat prompted many individuals to buy guns. Moreover, we show that new gun owners, even more than buyers who already owned guns, exhibit strong conspiracy and anti-system beliefs. These findings have substantial consequences for the subsequent population of gun owners and provide insight into how social disruptions can alter the nature of political groups.

The purpose of this investigation was to expand upon the limited existing research examining the test–retest reliability, cross-sectional validity and longitudinal validity of a sample of bioelectrical impedance analysis (BIA) devices as compared with a laboratory four-compartment (4C) model. Seventy-three healthy participants aged 19–50 years were assessed by each of fifteen BIA devices, with resulting body fat percentage estimates compared with a 4C model utilising air displacement plethysmography, dual-energy X-ray absorptiometry and bioimpedance spectroscopy. A subset of thirty-seven participants returned for a second visit 12–16 weeks later and were included in an analysis of longitudinal validity. The sample of devices included fourteen consumer-grade and one research-grade model in a variety of configurations: hand-to-hand, foot-to-foot and bilateral hand-to-foot (octapolar). BIA devices demonstrated high reliability, with precision error ranging from 0·0 to 0·49 %. Cross-sectional validity varied, with constant error relative to the 4C model ranging from −3·5 (sd 4·1) % to 11·7 (sd 4·7) %, standard error of the estimate values of 3·1–7·5 % and Lin’s concordance correlation coefficients (CCC) of 0·48–0·94. For longitudinal validity, constant error ranged from −0·4 (sd 2·1) % to 1·3 (sd 2·7) %, with standard error of the estimate values of 1·7–2·6 % and Lin’s CCC of 0·37–0·78. While performance varied widely across the sample investigated, select models of BIA devices (particularly octapolar and select foot-to-foot devices) may hold potential utility for the tracking of body composition over time, particularly in contexts in which the purchase or use of a research-grade device is infeasible.