A primer on the use of computational modelling to investigate affective states, affective disorders and animal welfare in non-human animals.

Objective measures of animal emotion-like and mood-like states are essential for preclinical studies of affective disorders and for assessing the welfare of laboratory and other animals. However, the development and validation of measures of these affective states poses a challenge partly because the relationships between affect and its behavioural, physiological and cognitive signatures are complex. Here, we suggest that the crisp characterisations offered by computational modelling of the underlying, but unobservable, processes that mediate these signatures should provide better insights. Although this computational psychiatry approach has been widely used in human research in both health and disease, translational computational psychiatry studies remain few and far between. We explain how building computational models with data from animal studies could play a pivotal role in furthering our understanding of the aetiology of affective disorders, associated affective states and the likely underlying cognitive processes involved. We end by outlining the basic steps involved in a simple computational analysis.

Worth the risk? Contemporary indications, yield and complications of lumbar punctures in a metropolitan Australian health service.

BACKGROUND: Performing lumbar punctures carries a risk of harm to the patient, but the information cerebrospinal fluid provides often makes this procedure necessary. Clinicians in the Australian setting would benefit from having more information on these procedures, in order to help them in a risk versus benefit analysis. AIMS: To describe the contemporary indications, cerebrospinal fluid findings and complications of lumbar punctures in a metropolitan Australian health service. METHODS: Retrospective electronic medical records audit of lumbar punctures performed on 525 adults within three acute hospitals between 1 July 2018 and 30 June 2019. Main outcome measures include frequency of indication for lumbar puncture by category, normal versus abnormal cerebrospinal fluid for each category, and frequency, severity and type of complications of lumbar punctures. RESULTS: Of 525 adult lumbar punctures that were assessed in this study, 466 were performed for a diagnostic indication. The most common diagnostic indications were acute severe headache (156 procedures; 33.5%) and encephalopathy (128 procedures; 27.5%). The yield of abnormal results varied by indication category, with the above indications yielding abnormal results in 85 (54.5%) and 72 (56.3%) cases respectively. A complication was recorded in 54 (10.3% of total) procedures. The majority (45; 8.6%) of complications were minor in severity and most frequently consisted of post-dural puncture headache (PDPH). CONCLUSIONS: In the era of an increased reliance on high quality neuroimaging, lumbar puncture has a high diagnostic yield with a low rate of major complications. The most common complication is PDPH, which is mild and self-limiting in most cases.

That brachycephalic look: Infant-like facial appearance in short-muzzled dog breeds.

Brachycephalic dog breeds are highly popular, yet their conformation-related disorders represent a major welfare concern. It has been suggested that the current popularity of such breeds can be explained by their cute, infant-like facial appearances. The concept of 'kindchenschema' refers to the observation that certain physical features of infant humans and other animals can automatically stimulate positive and nurturant feelings in adult observers. But the proposal that brachycephalic dogs possess heightened 'kindchenschema' facial features, even into adulthood, has never been formally investigated. Here, we hypothesised that relative muzzle shortening across a range of breeds would be associated with known 'kindchenschema' facial features, including a relatively larger forehead, larger eyes and smaller nose. Relative fronto-facial feature sizes in exemplar photographs of adult dogs from 42 popular breeds were measured and associated with existing data on the relative muzzle length and height-at-withers of the same breeds. Our results show that, in adulthood, shorter-muzzled breeds have relatively larger (taller) foreheads and relatively larger eyes (i.e. area of exposed eyeball relative to overall face area) than longer-muzzled breeds, and that this effect is independent of breed size. In sum, brachycephalic dog breeds do show exaggeration of some, but not all, known fronto-facial 'kindchenschema' features, and this may well contribute to their apparently cute appearance and to their current popularity as companion animals. We conclude that the challenge of addressing conformation-related disorders in companion dogs needs to take account of the cute, 'kindchenschema' looks that many owners are likely to be attracted to.

Are Brachycephalic Dogs Really Cute? Evidence from Online Descriptions.

Brachycephalic dog breeds have become increasingly popular in recent years, despite showing a high incidence of conformation-related disorders and early mortality. It has been suggested that this popularity might be explained by public perceptions of these short-muzzled dogs as looking particularly infant-like or "cute." Here, the hypothesis that short-muzzled breeds are especially likely to be described as cute was investigated by analyzing the word contents of advertisements for dogs and puppies being sold online. The ages and breeds of dogs being advertised were considered, in addition to whether the text of each advertisement included the word "cute" or two associated words: "adorable" and "sweet." Analyses of the entire sample of advertisements (n = 43,312) indicated that younger dogs were more likely to be advertised as "cute" and "adorable," while older ones were more likely to be advertised as "sweet." Shortmuzzled, brachycephalic breeds (cranio-facial ratio < 0.5) were more likely to be advertised as "cute," with brachycephalic puppies under 6 months of age being particularly likely to be called "cute" and also "adorable." However, breed size had a larger and wider effect on word use in advertisements, with smaller dogs being advertised more frequently using all three words: "cute," "adorable," and "sweet." When data for adult dogs only were considered (n = 11,400), and continuous muzzle shortening and age data were used, a somewhat different and more complex pattern of results were found. Use of the words "cute" and "adorable" were not associated with degree of muzzle shortening among these adult dogs, but "sweet" was used more often in advertisements for longer-muzzled breeds. We conclude that the present dataset provides partial support for the assertion that short-muzzled dogs are described as more "cute" than longer-muzzled ones, but that small size is a better predictor of the use of "cute" and its synonyms.

Magnetic Fields with Precise Quasisymmetry for Plasma Confinement.

Quasisymmetry is an unusual symmetry that can be present in toroidal magnetic fields, enabling the confinement of charged particles and plasma. Here it is shown that both quasiaxisymmetry and quasihelical symmetry can be achieved to a much higher precision than previously thought over a significant volume, resulting in exceptional confinement. For a 1 Tesla mean field far from axisymmetry (vacuum rotational transform >0.4), symmetry-breaking mode amplitudes throughout a volume of aspect ratio 6 can be made as small as the typical ∼50 µT geomagnetic field.

Dissecting the links between reward and loss, decision-making, and self-reported affect using a computational approach.

Links between affective states and risk-taking are often characterised using summary statistics from serial decision-making tasks. However, our understanding of these links, and the utility of decision-making as a marker of affect, needs to accommodate the fact that ongoing (e.g., within-task) experience of rewarding and punishing decision outcomes may alter future decisions and affective states. To date, the interplay between affect, ongoing reward and punisher experience, and decision-making has received little detailed investigation. Here, we examined the relationships between reward and loss experience, affect, and decision-making in humans using a novel judgement bias task analysed with a novel computational model. We demonstrated the influence of within-task favourability on decision-making, with more risk-averse/'pessimistic' decisions following more positive previous outcomes and a greater current average earning rate. Additionally, individuals reporting more negative affect tended to exhibit greater risk-seeking decision-making, and, based on our model, estimated time more poorly. We also found that individuals reported more positive affective valence during periods of the task when prediction errors and offered decision outcomes were more positive. Our results thus provide new evidence that (short-term) within-task rewarding and punishing experiences determine both future decision-making and subjectively experienced affective states.

Space, feature, and risk sensitivity in homing pigeons (Columba livia): Broadening the conversation on the role of the avian hippocampus in memory.

David Sherry has been a pioneer in investigating the avian hippocampal formation (HF) and spatial memory. Following on his work and observations that HF is sensitive to the occurrence of reward (food), we were interested in carrying out an exploratory study to investigate possible HF involvement in the representation goal value and risk. Control sham-lesioned and hippocampal-lesioned pigeons were trained in an open field to locate one food bowl containing a constant two food pellets on all trials, and two variable bowls with one containing five pellets on 75% (High Variable) and another on 25% (Low Variable) of their respective trials (High-Variable and Low-Variable bowls were never presented together). One pairing of pigeons learned bowl locations (space); another bowl colors (feature). Trained to color, hippocampal-lesioned pigeons performed as rational agents in their bowl choices and were indistinguishable from the control pigeons, a result consistent with HF regarded as unimportant for non-spatial memory. By contrast, when trained to location, hippocampal-lesioned pigeons differed from the control pigeons. They made more first-choice errors to bowls that never contained food, consistent with a role of HF in spatial memory. Intriguingly, the hippocampal-lesioned pigeons also made fewer first choices to both variable bowls, suggesting that hippocampal lesions resulted in the pigeons becoming more risk averse. Acknowledging that the results are preliminary and further research is needed, the data nonetheless support the general hypothesis that HF-dependent memory representations of space capture properties of reward value and risk, properties that contribute to decision making when confronted with a choice.

Characterization of Phages YuuY, KaiHaiDragon, and OneinaGillian Isolated from Microbacterium foliorum.

Microbacterium foliorum is a Gram-positive bacteria found in organic matter. Three lytic bacteriophages, KaiHaiDragon, OneinaGillian, and YuuY, were isolated from M. foliorum strain NRRL B-24224. Phage YuuY in particular expresses a broad host range as it possesses the ability to infect closely related bacterial species Microbacterium aerolatum at a high plating efficiency. Characterization tests were performed on all three Microbacterium phage to assess morphology, genomic characteristics, pH and thermal stabilities, life cycle, and the type of receptor used for infection. All three phages showed similar pH stability, ranging from pH 5-11, except for KaiHaiDragon, which had a reduced infection effectiveness at a pH of 11. YuuY possessed a significantly higher temperature tolerance compared to the other Microbacterium phages as some phage particles remained viable after incubation temperatures of up to 80 °C. Based on the one-step growth curve assay, all three Microbacterium phages possessed a relatively short latent period of 90 min and an approximately two-fold burst size factor. Moreover, all three phages utilize a carbohydrate receptor to initiate infection. Based on bioinformatics analysis, YuuY, KaiHaiDragon and OneinaGillian were assigned to clusters EA10, EC, and EG, respectively.

Using Primary Reinforcement to Enhance Translatability of a Human Affect and Decision-Making Judgment Bias Task.

Good translatability of behavioral measures of affect (emotion) between human and nonhuman animals is core to comparative studies. The judgment bias (JB) task, which measures "optimistic" and "pessimistic" decision-making under ambiguity as indicators of positive and negative affective valence, has been used in both human and nonhuman animals. However, one key disparity between human and nonhuman studies is that the former typically use secondary reinforcers (e.g., money) whereas the latter typically use primary reinforcers (e.g., food). To address this deficiency and shed further light on JB as a measure of affect, we developed a novel version of a JB task for humans using primary reinforcers. Data on decision-making and reported affective state during the JB task were analyzed using computational modeling. Overall, participants grasped the task well, and as anticipated, their reported affective valence correlated with trial-by-trial variation in offered volume of juice. In addition, previous findings from monetary versions of the task were replicated: More positive prediction errors were associated with more positive affective valence, a higher lapse rate was associated with lower affective arousal, and affective arousal decreased as a function of number of trials completed. There was no evidence that more positive valence was associated with greater "optimism," but instead, there was evidence that affective valence influenced the participants' decision stochasticity, whereas affective arousal tended to influence their propensity for errors. This novel version of the JB task provides a useful tool for investigation of the links between primary reward and punisher experience, affect, and decision-making, especially from a comparative perspective.

State-dependent judgement bias in Drosophila: evidence for evolutionarily primitive affective processes.

Affective states influence decision-making under ambiguity in humans and other animals. Individuals in a negative state tend to interpret ambiguous cues more negatively than individuals in a positive state. We demonstrate that the fruit fly, Drosophila melanogaster, also exhibits state-dependent changes in cue interpretation. Drosophila were trained on a Go/Go task to approach a positive (P) odour associated with a sugar reward and actively avoid a negative (N) odour associated with shock. Trained flies were then either shaken to induce a purported negative state or left undisturbed (control), and given a choice between: air or P; air or N; air or ambiguous odour (1 : 1 blend of P : N). Shaken flies were significantly less likely to approach the ambiguous odour than control flies. This 'judgement bias' may be mediated by changes in neural activity that reflect evolutionarily primitive affective states. We cannot say whether such states are consciously experienced, but use of this model organism's versatile experimental tool kit may facilitate elucidation of their neural and genetic basis.

Animal emotion: Descriptive and prescriptive definitions and their implications for a comparative perspective.

In recent years there has been a growing research interest in the field of animal emotion. But there is still little agreement about whether and how the word "emotion" should be defined for use in the context of non-human species. Here, we make a distinction between descriptive and prescriptive definitions. Descriptive definitions delineate the ways in which the word emotion is used in everyday life. Prescriptive definitions are used to pick out the set of events that scientific theories of emotion purport to explain. Picking out three prescriptive definitions, we show that the different ways in which emotions are defined correspond to processes that are distributed differentially across the animal kingdom. We propose that these definitions provide a useful starting point for investigating the varying emotional capacities of a wide range of animals, providing a basis for a new, comparative science of emotion.

Examining affective structure in chickens: valence, intensity, persistence and generalization measured using a Conditioned Place Preference Test.

When measuring animals' valenced behavioural responses to stimuli, the Conditioned Place Preference (CPP) test goes a step further than many approach-based and avoidance-based tests by establishing whether a learned preference for, or aversion to, the location in which the stimulus was encountered can be generated. We designed a novel, four-chambered CPP test to extend the capability of the usual CPP paradigm to provide information on four key features of animals' affective responses: valence, scale, persistence and generalization. Using this test, we investigated the affective responses of domestic chickens (Gallus gallus domesticus) to four potentially aversive stimuli: 1. Puffs of air; 2. Sight of (robotic) snake; 3. Sprays of water; 4. Sound of conspecific alarm calls. We found conditioned avoidance of locations associated with the air puffs and water sprays (Friedman's χ2 (3) = 13.323 p > .005; χ2 (3) = 14.235 p > .005), but not with the snake and alarm calls. The scale of the learned avoidance was similar for the air puff and water spray stimuli, but persistence and generalization differed. We conclude that the four chambered CPP test can have a valuable role to play in making multi-feature measurements of stimulus-generated affective responses, and we highlight the value of such measurements for improving our understanding of the structure of affect in chickens and other animals.

A Rare Case of NUT Carcinoma of the Thyroid.

NUT carcinoma is an aggressive, poorly differentiated squamous cell carcinoma, defined by rearrangement of the NUTM1 (Nuclear Protein in Testis) gene. Diagnosis is challenging due to histologic similarities with other poorly differentiated tumors requiring advanced diagnostic techniques. There is no established treatment, and prognosis remains extremely poor. A 27-year-old woman without known medical history presented with a rapidly enlarging neck mass and compressive symptoms. Chemotherapy for presumed squamous cell carcinoma with a component of anaplastic thyroid cancer based on pathology was initiated. Next-generation sequencing revealed thyroid NUT carcinoma with high PD-L1 expression, prompting PD-1 targeted therapy. The patient expired shortly afterwards from progressive disease. NUT carcinoma of thyroid origin is an extremely rare disease. This case brings awareness to the disease, highlights the importance of advanced diagnostic techniques and complexities in managing patients with NUT carcinoma.

Exploring the similarities between risk factors triggering depression in humans and elevated in-cage "inactive but awake" behavior in laboratory mice.

Introduction: Depression is a human mental disorder that can also be inferred in non-human animals. This study explored whether time spent inactive but awake ("IBA") in the home-cage in mice was further triggered by risk factors similar to those increasing vulnerability to depression in humans (early life stress, genetic predispositions, adulthood stress). Methods: Eighteen DBA/2 J and 18 C57BL/6 J females were tested, of which half underwent as pups a daily maternal separation on post-natal days 2-14 (early-life stress "ELS") (other half left undisturbed). To assess the effect of the procedure, the time the dams from which the 18 subjects were born spent active in the nest (proxy for maternal behavior) was recorded on post-natal days 2, 6, 10 and 14 for 1 h before separation and following reunion (matched times for controls), using live instantaneous scan sampling (total: 96 scans/dam). For each ELS condition, about half of the pups were housed post-weaning (i.e., from 27 days old on average) in either barren (triggering IBA and depression-like symptoms) or larger, highly enriched cages (n = 4-5 per group). Time mice spent IBA post-weaning was observed blind to ELS treatment using live instantaneous scan sampling in two daily 90-min blocks, two days/week, for 6 weeks (total: 192 scans/mouse). Data were analyzed in R using generalized linear mixed models. Results: The dams were significantly more active in the nest over time (p = 0.016), however with no significant difference between strains (p = 0.18), ELS conditions (p = 0.20) and before/after separation (p = 0.83). As predicted, post-weaning barren cages triggered significantly more time spent IBA in mice than enriched cages (p < 0.0001). However, neither ELS (p = 0.4) nor strain (p = 0.84) significantly influenced time mice spent IBA, with no significant interaction with environmental condition (ELS × environment: p = 0.2861; strain × environment: p = 0.5713). Discussion: Our results therefore only partly support the hypothesis that greater time spent IBA in mice is triggered by risk factors for human depression. We discuss possible explanations for this and further research directions.

Membrane-coated glass electrodes for stable, low-noise electrophysiology recordings in Drosophila central neurons.

BACKGROUND: Electrophysiological recording with glass electrodes is one of the best techniques to measure membrane potential dynamics and ionic currents of voltage-gated channels in neurons. However, artifactual variability of the biophysical state variables that determine recording quality can be caused by insufficient affinity between the electrode and cell membrane during the recording. NEW METHOD: We introduce a phospholipid membrane coating on glass electrodes to improve intracellular electrophysiology recording quality. Membrane-coated electrodes were prepared with a tip-dip protocol for perforated-patch, sharp-electrode current-clamp, and cell-attached patch-clamp recordings from specific circadian clock neurons in Drosophila. We perform quantitative comparisons based on the variability of functional biophysical parameters used in various electrophysiological methods, and advanced statistical comparisons based on the degree of stationariness and signal-to-noise ratio. RESULTS: Results indicate a dramatic reduction in artifactual variabilities of functional parameters from enhanced stability. We also identify significant exclusions of a statistically estimated noise component in a time series of membrane voltage signals, improving signal-to-noise ratio. COMPARISON WITH EXISTING METHODS: Compared to standard glass electrodes, using membrane-coated glass electrodes achieves improved recording quality in intracellular electrophysiology. CONCLUSIONS: Electrophysiological recordings from Drosophila central neurons can be technically challenging, however, membrane-coated electrodes will possibly be beneficial for reliable data acquisition and improving the technical feasibility of axonal intracellular activities measurements and single-channel recordings. The improved electrical stability of the recordings should also contribute to increased mechanical stability, thus facilitating long-term stable measurements of neural activity. Therefore, it is possible that membrane-coated electrodes will be useful for any model system.

Developing guidelines for pet rat housing through expert consultation.

BACKGROUND: Pet care guidelines play an important role in ensuring that owners are well informed about good husbandry practices, allowing them to provide the best care for their animals. However, the development of such guidelines is difficult when there is little appropriate empirical evidence on which to base guidelines, as in the case of pet rats. The consultation of multiple experts can help to surmount this challenge. METHODS: We developed a set of guidelines for pet rat housing by consulting with a group of experts, including veterinarians, veterinary nurses, animal welfare scientists and experienced pet rat owners. The consultation involved two rounds of online surveys (n = 13) and one online discussion (n = 8). RESULTS: The resulting guidelines cover a broad range of features within pet rat housing, including injury prevention, details of suitable refuges and substrates, and suitable cage sizing. The guidelines may evolve as more information about pet rats comes to light but may nonetheless provide a useful starting point for any future guidelines. CONCLUSIONS: At present, these guidelines may not only be useful for pet rat owners and those advising pet rat owners, such as veterinarians, but may also be useful in the design of housing, including for laboratory rodents.

A mapping review of refinements to laboratory rat housing and husbandry.

Refining the housing and husbandry of laboratory rats is an important goal, both for ethical reasons and to allow better quality research. We conducted a mapping review of 1,017 studies investigating potential refinements of housing and husbandry of the laboratory rat to assess what refinements have, and have not, been studied, and to briefly assess whether there is evidence to support any impact on rat welfare. Among the many refinements studied, the majority involve changes to the cage, but some also involve alterations to the wider environment. The effects of these refinements were assessed using a range of readouts, many of which are difficult to interpret from a welfare perspective. Preference studies, which are easier to interpret, provide evidence that rats prefer complex environments, including shelters and multiple objects, which offer different areas/resources allowing the rat to engage in diverse behaviors. The reporting of methodology in papers was often poor, indicating that studies were potentially subject to biases. Given that many refinements co-occurred, it was often difficult to tease apart which ones were most beneficial for rat welfare. Effects of refinements were also moderated by a number of factors including age, sex, strain and photoperiod. Altogether our findings show that a one-size-fits-all approach to refinements is not appropriate, because different refinements will impact different rats in different ways. Our review has also produced a database of >1,000 articles that can be used for further and more detailed analyses. Our findings have also highlighted areas where future research is likely to be valuable, including refinements to rat transport, handling and the use of training.

Bridging the Gap: Human Emotions and Animal Emotions.

Our experiences of the conscious mental states that we call emotions drive our interest in whether such states also exist in other animals. Because linguistic report can be used as a gold standard (albeit indirect) indicator of subjective emotional feelings in humans but not other species, how can we investigate animal emotions and what exactly do we mean when we use this term? Linguistic reports of human emotion give rise to emotion concepts (discrete emotions; dimensional models), associated objectively measurable behavioral and bodily emotion indicators, and understanding of the emotion contexts that generate specific states. We argue that many animal studies implicitly translate human emotion concepts, indicators and contexts, but that explicit consideration of the underlying pathways of inference, their theoretical basis, assumptions, and pitfalls, and how they relate to conscious emotional feelings, is needed to provide greater clarity and less confusion in the conceptualization and scientific study of animal emotion.

Online Dog Sale Advertisements Indicate Popularity of Welfare-Compromised Breeds.

Kennel club registrations have been used in a number of studies to estimate ownership levels and fashion trends among dog breeds. They cannot, however, give a complete overview of the contemporary trade in pet dogs, and additionally, may be particularly poor at monitoring trends among some welfare-vulnerable breeds. Here, we compared data from online advertisements for the UK sales of single-breed dogs over an 18-month period, with equivalent data (including for prior and subsequent years) from the UK Kennel Club. Kennel Club registration rates and breed popularity rates online were positively correlated. However, some breeds, including the Jack Russell terrier, Border collie and Chihuahua were considerably over-represented in online advertisements when compared with Kennel Club registrations, indicating a hidden market for certain breeds. In addition, the online dataset provided information on the sale and re-homing of adult dogs, showing high rates of adult homing of the Staffordshire bull terrier, Siberian husky and Rottweiler. We conclude that online pet-sales websites are an important and complementary source of data about the market in, and popularity of, a wide range of dog breeds.

Cardiovascular health care and health literacy among immigrants in Europe: a review of challenges and opportunities during the COVID-19 pandemic.

Objectives: Europe is a destination for many migrants, a group whose proportion of the overall population will increase over the next decades. The cardiovascular (CV) risk distribution and outcomes, as well as health literacy, are likely to differ from the host population. Challenges related to migrant health status, cardiovascular risk distribution and health literacy are compounded by the ongoing coronavirus disease 2019 (COVID-2019) crisis. Methods: We performed a narrative review of available evidence on migrant CV and health literacy in Europe. Results: Health literacy is lower in migrants but can be improved through targeted interventions. In some subgroups of migrants, rates of cardiovascular disease (CVD) risk factors, most importantly hypertension and diabetes, are higher. On the other hand, there is strong evidence for a so-called healthy migrant effect, describing lower rates of CV risk distribution and mortality in a different subset of migrants. During the COVID-19 pandemic, CV risk factors, as well as health literacy, are key elements in optimally managing public health responses in the ongoing pandemic. Conclusions: Migrants are both an opportunity and a challenge for public health in Europe. Research aimed at better understanding the healthy migrant effect is necessary. Implementing the beneficial behaviors of migrants could improve outcomes in the whole population. Specific interventions to screen for risk factors, manage chronic disease and increase health literacy could improve health care for migrants. This pandemic is a challenge for the whole population, but active inclusion of immigrants in established health care systems could help improve the long-term health outcomes of migrants in Europe.