Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by acute attacks. High-dose steroids (HDS) are the primary treatment, with no significant differences between oral and intravenous (IV) routes. However, factors influencing route selection and attack characteristics leading to treatment remain unclear. This study assesses trends in oral vs. IV HDS use, factors affecting decisions, and clinical impact. Methods: We retrospectively analyzed data from the Multiple Sclerosis database (MuSicaL) using Natural Language Processing (NLP) from 2010–2022. We examined annual trends in HDS route, its relationship with attack type, and prescribing specialties. Statistical analyses were conducted using R-4.2.2. Results: Of 2,413 individuals meeting inclusion criteria, 1,086 had an attack, and 543 (50%) used HDS. Among 265 with a known route, oral HDS was most common, and HDS use declined after 2018. Attack type significantly influenced HDS route (p = 0.045), with IV use highest in multifocal subtype (50.9%) and lowest in myelitis (32.7%). Neurologists were the primary prescribers of IV HDS. Conclusions: Our results indicate a trend towards increased oral HDS use, with IV reserved for severe attacks like multifocal ones. Attack type influences treatment choices, and neurologists remain key prescribers of IV HDS, guiding future treatment strategies.

Background: Long-term efficacy of inebilizumab (INEB), an anti-CD19+ B cell-depleting antibody approved for the treatment of seropositive-aquaporin-4-antibody (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) was evaluated over N-MOmentum (NCT02200770) open-label period (OLP) vs azathioprine and other immunosuppressants (AZA/IST) and vs PBO. Methods: Two historical comparator groups (HCGs), AZA/IST (N=132) and PBO (N=106), derived from published NMOSD studies, were used to compare efficacy of INEB (N=208) over the OLP. Hazard ratios (HR) for INEB vs HCGs were estimated using Cox proportional hazards (PH) regression. Time to NMOSD attack was analysed using parametric and flexible survival (spline) models. Results: Time to NMOSD attack for N-MOmentum PBO compared to PBO was HR 1.15;(95% CI:0.67–1.91; P=0.58). The HRs for time to NMOSD attack for INEB vs AZA/IST and PBO groups were 0.29(95% CI:0.17, 0.42; P<0.001) and 0.15 (95% CI:0.10, 0.21; P<0.001). At 4 years, estimated attack-free survival was 77% (95% CI:71, 83) for INEB, 36% (95% CI:27, 46) for AZA/IST, and 12% (95% CI:7, 20) for PBO. Conclusions: INEB was associated with a statistically significant reduction in risk of an NMOSD attack and provided a long-term attack-free probability over the OLP compared to the relative short-term benefit observed with AZA/IST.

Background: The long-term outcomes of inebilizumab in participants from the N-MOmentum trial with a history of immunosuppressant therapy as compared to those without was evaluated. Methods: N-MOmentum (NCT02200770) was a 28-week randomized phase 2/3 trial of inebilizumab vs placebo, with an optional Open-Label Period (OLP) (>2 years). In this post hoc analysis, AQP4+ participants who received inebilizumab (through the OLP) were grouped by no history of immunosuppression therapy beyond treatment of acute NMOSD attacks (naïve), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy. Results: Among participants who received inebilizumab during the study, 94 received prior AZA/MMF and 103 were immunosuppressant naïve. Annualized relapse rate (95%CI) for participants with prior AZA/MMF was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for naïve. The hospitalization rate (annualized rate [95% CI]) for prior AZA/MMF was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for naïve. Participants with ≥1 study drug-related-treatment-emergent-adverse-event (TEAE) was 30.9% (29/94) in prior AZA/MMF and 46.6% (48/103) of naïve. Most adverse events were infection-related for both groups; 72.3% (68/94) for prior AZA/MMF and 77.7% (80/94) for naïve. Conclusions: This post hoc analysis evaluating long-term outcomes of inebilizumab in AQP4+ NMOSD participants treated with prior AZA/MMF therapy demonstrated a similar efficacy and safety profile as participants without prior immunosuppressant therapy.

Background: SMA affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 pre-mRNA splicing modifier. Methods: SUNFISH is a multicenter, two-part, randomized, placebo-controlled, double-blind study in patients with Types 2/3 SMA. Part 1 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Types 2/3 SMA. Part 2 assessed the efficacy and safety of the selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. In Part 2, participants were treated with risdiplam or placebo for 12 months, then received risdiplam in a blinded manner until month 24. At month 24, patients were offered the opportunity to enter the open-label extension phase. Results: Change from baseline in MFM32 total score (Part 2- primary endpoint) in patients treated with risdiplam versus placebo was met at month 12. These increases in motor function were sustained in the second and third year after risdiplam treatment. Here we present 4-year efficacy and safety data from SUNFISH. Conclusions: SUNFISH is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of individuals with SMA.

Two distinct approaches have emerged for the assessment of quality of life (QoL) and welfare in domestic dogs. One approach, which has so far been applied only to companion dogs, is derived from proxy assessment of QoL in human beings, with the owner or veterinarian acting as the proxy. Because dogs are a different species to human beings, assessment by proxy is even more challenging than when the subject being assessed is human. Our evaluation of published studies indicates that existing canine QoL instruments are imperfect, in part because of avoidable deficiencies such as failure to define QoL and using measures of health status as sole indicators of QoL. The second approach to QoL assessment, which stems from animal welfare science, is based upon objective measurement of behaviour and stress physiology, and has been applied mainly to dogs in laboratory and rescue kennels. We review these and our own recent studies, and conclude that although interpretation of signs of acute stress may be relatively straightforward, signs of chronic stress such as stereotypic behaviour require further research before they can be incorporated into QoL measures. So far, there has been little attempt to integrate proxy assessment with objective measures. We recommend that this integration would be beneficial. Fundamentally, both approaches aim to describe and quantify aspects of some inner state of well-being, and it should eventually be possible to map each on to the other.

Historically, pet dogs were trained using mainly negative reinforcement or punishment, but positive reinforcement using rewards has recently become more popular. The methods used may have different impacts on the dogs’ welfare. We distributed a questionnaire to 364 dog owners in order to examine the relative effectiveness of different training methods and their effects upon a pet dog's behaviour. When asked how they trained their dog on seven basic tasks, 66% reported using vocal punishment, 12% used physical punishment, 60% praise (social reward), 51% food rewards and II% play. The owner's ratings for their dog's obedience during eight tasks correlated positively with the number of tasks which they trained using rewards (P< 0.01), but not using punishment (P = 0.5). When asked whether their dog exhibited any of 16 common problematic behaviours, the number of problems reported by the owners correlated with the number of tasks for which their dog was trained using punishment (P< 0.001), but not using rewards (P = 0.17). Exhibition of problematic behaviours may be indicative of compromised welfare, because such behaviours can be caused by— or result in — a state of anxiety and may lead to a dog being relinquished or abandoned. Because punishment was associated with an increased incidence of problematic behaviours, we conclude that it may represent a welfare concern without concurrent benefits in obedience. We suggest that positive training methods may be more useful to the pet-owning community.

The objective was to evaluate the welfare implications of electrical stunning prior to gill-cutting of farmed African catfish as an alternative to live chilling in combination with gutting. Electroencephalogram (EEG) and electrocardiogram (ECG) recordings, in combination with observation of behaviour and responses to noxious stimuli, were used to assess brain and cardiac function in African catfish (body-weight 1571 ± 362 g [mean ± standard deviation], 32 males and 26 females). In the first experiment, the minimum electrical current required to induce a general epileptiform insult by head-only stunning was determined. The individual catfish were fixed in a specially designed restrainer, and applied voltages of 150 V, 200 V, 250 V, 300 V or 350 V (50 Hz AC) were delivered via scissor-model stunning tongs for approximately I s. A general epileptiform insult was observed in 31 fish, for which a successful EEG recording was obtained using 362 ± 32 V, 629 ± 180 mA for 1.2 s. The durations of the tonic, the clonic and the exhaustion phases were 8 ± 3 s, 12 ± 7 s and 7 ± 5 s as measured by EEG, respectively; a distinct exhaustion phase was not clear in II fish. The total duration of the insult was 23 ± 8 s. After the insult the fish recovered. The heart rate was 63 ± 29 beats min I prior to stunning. After stunning, the ECG revealed extrasystole and was irregular. By using an average current of 629 ± 180 mA (at approximately 360 V, 50 Hz AC), at least 91% of fish are effectively stunned with a confidence level of 95%. In the second experiment, the behaviour of 10 individual catfish, which were able to move freely in water, was observed following head-only stunning (370 V). The durations of the tonic, clonic and exhaustion phases in free-swimming fish were II ± 8 s, 20 ± 5 s and 23 ± 20 s, respectively. All fish recovered. In the third experiment, a group of seven catfish was head-only stunned followed by gill-cutting to kill them as a second procedure (ie after recovery from head-only stunning). No brain activity was seen on the EEG 12 ± 5 s after stunning. However, two fish showed responses to noxious stimuli after 2 min and 5 min. A second group of seven catfish was gill-cut only. They responded to noxious stimuli for at least 15 min. The blood loss was 1.2% and I.0% of live weight for the first and second group, respectively. It may be concluded from our results that African catfish are effectively stunned for 23 ± 8 s with a current of 629 ± 180 mA for 1.2 s, after which they recover. Since evoked responses may remain for at least 5 min after stunning and gill-cutting, we recommended that the stunning and killing procedure should be optimised.

Commercially reared ostrich chicks are typically kept in barren, indoor environments. This experiment investigated the effects of environmental enrichment on the pecking behaviour, exploration, food consumption and novelty responses of ostrich chicks aged 10 to 21 days. Four groups of 20 randomly selected ostrich chicks were housed in heated huts at one day of age (Day 1), and at Day 10 were allowed access to sand-covered areas (30 m2) that were either barren (control: n = 2 groups) or enriched with cabbage, coniferous cones and sticks (enriched: n = 2 groups). Pecking behaviour was recorded by focal sampling the behaviour of five chicks per group for four 5 min periods per day on Day 10 and Day 13. All enriched chicks pecked at the cabbage, of which they consumed considerable amounts (26 ± 3 g/chick/day). The enriched chicks did not have higher overall pecking frequencies but tended to peck less at fixtures in the pen, compared to control chicks. Additionally, the enriched chicks showed increased exploration in terms of the percentage of chicks observed outside the heated huts. In a novel object test, enriched chicks stayed closer to and delivered more pecks at sorrel (Rumex acetosa) than did control chicks, whereas there was no difference between the treatment groups in their response to adult ostrich feathers. Enriched chicks consumed more food (79 ± 0.4 g/chick/day) than did control chicks (67 ± 09 g/chick/day) during the experimental period. We suggest that environmental enrichment improves the welfare of ostrich chicks in terms of increasing exploration and reducing pecking at fixtures in the pen, without compromising food consumption.

Since animal minds are private, so their perception of their own quality of life (QoL) must be also. Anthropocentrism, the interpretation of reality exclusively in terms of human values and experience, has to be guarded against in any assessment of animal welfare; for domestic pets, misapprehensions about their olfactory and cognitive abilities appear to present the greatest challenge to their welfare. Anthropomorphism, the attribution of human qualities to animals, presents a particular problem when considering companion animals, since most bonds between owners and their pets appear to be based upon a perception of the pet as almost human. Many owners report that their dogs, cats and horses are capable of feeling complex emotions, such as pride and guilt, that require a level of self-awareness that has been difficult to demonstrate even in chimpanzees. Such beliefs appear to contribute to the development of behavioural disorders in pets; for example, clinical experience suggests that the application of punishment by owners who attribute ‘guilt’ to their animals may unwittingly lead to compromised welfare. Anthropomorphic owners are also likely to be poor proxies for reporting their pets' QoL.

For monitoring purposes there is a need for a protocol to measure foot-pad dermatitis (FPD) on-farm. Therefore, we studied the effect of number of birds sampled, number of locations sampled and sampling location in a broiler house on the accuracy of measurement, in order to construct a protocol that can be applied in practice. Samples were taken from eight commercial flocks (Ross 308) at up to ten locations with up to 25 birds sampled per location. Foot-pad lesions were scored in all birds for both feet using the Swedish scoring method. No significant differences in FPD score were found between the first five birds and all birds sampled at a particular location. Although locations near the walls did not differ in FPD score from locations in the central area of a house, the severity of foot-pad lesions was unevenly distributed over the house. A model was constructed showing the inaccuracy related to the number of locations sampled in the house and the number of birds sampled per location. The model shows that in situations with at least five locations differences in inaccuracy are relatively small when a total of 100 birds or more is sampled. Inaccuracy is largest in a flock with variation in foot-pad scores, as compared to flocks with little variation. The results of this experiment can be used to determine the optimal sample size in a commercial broiler house.

A recent FAWC report introduced ‘a life worth living’ as a useful concept in farm animal welfare discussions and policy. But what does this concept mean? And is it a useful one? This paper extends FAWC's approach in several ways. It firstly provides an account of the concept of a life worth living in more detail, in relation to current animal welfare thinking, such as experiences and quality of life. It then describes how the concept might be applied in animal welfare management decisions and in setting standards for regulations and Farm Assurance schemes. The paper identifies several advantages to the concept: it is animal-based, intuitively understandable, and has direct prescriptive force in decision-making. But the concept also has certain limitations, especially that it is potentially complex and subjective and that it cannot include all ethically relevant concerns about farm animal welfare. Nevertheless, the paper concludes that the concept may become a useful addition to welfare dialogue, and finishes by identifying the core areas where further work is necessary.

These books, different in style and content but united in purpose and major conclusions, analyse events from 2007 to 2010 to ascertain why the economic disaster happened and what must be done to put the United States economy (on which both books focus) on a more secure footing, and prevent any recurrence of the extended crisis of those years. Both target the increasing influence of market liberalism over the last 30 years, and the institutions of capitalist economies which they have encouraged. Taylor focuses more on the regulation of the international financial sector, and Palley on labour market policy. They agree that both need to be addressed if the United States economy is to be restored to health. Both argue that growing income inequality in the US must be reversed before the US economy can significantly improve. Finally, they stress the interrelationship between political ideology and economic explanation, and argue that value free positive economics is a myth.

Policy-making concerned with animals often includes human interests, such as economy, trade, environmental protection, disease control, species conservation etc. When it comes to the interests of the animals, such policy-making often makes use of the results of animal welfare science to provide assessments of ethically relevant concerns for animals. This has provided a scientific rigour that has helped to overcome controversies and allowed debates to move forward according to generally agreed methodologies. However, this focus can lead to policies leaving out other important issues relevant to animals. This can be considered as a problem of what is included in welfare science, or of what is included in policy. This suggests two possible solutions: expanding animal welfare science to address all ethical concerns about animals’ interests or widening the perspective considered in policymaking to encompass other important ethical concerns about animals than welfare. The latter appears the better option. This requires both a ‘philosophy of animal welfare science’, a ‘philosophy of decision-making about animals’, and greater transparency about what is included or excluded from both animal welfare science and the politics of animal policy.

In humans, empathy has emotional and cognitive components, both of which are linked to caring and nurturant behaviour. Variations in each of these facets of empathy were likely to have been accessible to natural selection during the evolution of Homo, although the likely details of their respective adaptive values has so far only been considered in the context of intraspecific (human-human) behaviour. We propose that evolutionary psychology may provide a useful additional framework for examining why humans feel empathy for certain animals but not others. Phobias towards noxious animals, such as snakes and spiders, have been explained in terms of gene-culture co-evolution, but the possibility of an analogous ‘biophilia’ directed towards other animals has received less attention. The redirection of primarily intraspecific nurturant behaviour towards the young of non-human species may be a general human trait since it is practiced in a wide variety of cultures, including hunter-gatherers, and may arise from the merging of natural history and social intelligences that the archaeologist Steven Mithen suggests evolved ~100,000 years before present (YBP). The visual stimuli that evoke such nurturant behaviour, Lorenz's ‘Kindschenschema’, or ‘cuteness’, have been compared with the super-stimuli whereby parasitic cuckoos induce care-giving from their hosts, but recent evidence suggests that human females of childbearing age are especially sensitised to respond most strongly to characteristics of human infants, and may correspondingly become less attracted towards ‘cute’ animals. It is also possible that during human prehistory, the ability to care for young animals was selected for, in adolescent females, as an honest indicator of future quality as a mother. An ability to empathise with animals may also have given certain individuals and/or groups of kin an evolutionary advantage in hunting, and subsequently herding and domesticating, animals. Concern for animal welfare may therefore stem from an evolved human trait, even though its degree and extent of expression are undoubtedly strongly influenced by culture.

Background: Some patients do poorly despite small infarcts after endovascular therapy(EVT) whilst others with large infarcts do well. We validated exploratory findings from the ESCAPE trial regarding factors associated with such discrepancies, in the ESCAPE-NA1 trial(NCT02930018). Methods: We identified “discrepant cases” with modified Rankin Scale(mRS)≥3 despite small follow-up infarct volume(FIV≤25th-percentile) on 24-hour CT/MRI or mRS≤2 despite large FIV(volume≥75th-percentile). We compared area-under-the-curve(AUC) of pre-specified logistic models containing (a)pre-treatment factors(age/cancer/vascular risk-factors) and (b)treatment-related/post-treatment factors(serious adverse events/SAEs) in identifying small-FIV/mRS≥3 and large-FIV/mRS≤2, with stepwise regression-derived models. Results: Among 1,091 patients, 42/287(14.6%) with FIV≤7mL(25th-percentile) had mRS≥3; 65/275(23.6%) with FIV≥92mL(75th-percentile) had mRS≤2. Pre-specified pre-treatment factors(age/cancer/vascular risk-factors) were associated with FIV≤7mL/mRS≥3; stepwise models selected similar variables(similar AUCs:0.92-0.93,p=0.42). SAEs(infarct-in-new-territory/recurrent stroke/pneumonia/heart failure) were strongly associated with FIV≤7mL/mRS≥3; stepwise models also identified onset-to-needle time and hemoglobin(24-hours) as treatment-related/post-treatment factors(similar AUCs:0.92-0.94,p=0.14). Younger age was associated with FIV≥92mL/mRS≤2; stepwise models also selected diabetes absence and baseline hemoglobin(similar AUCs:0.76-0.77,p=0.82). Absence of SAEs(stroke progression/pneumonia/intracerebral hemorrhage) was strongly associated with FIV≥92mL/mRS≤2; stepwise models also identified 24-hour hemoglobin, glucose, and BP(similar AUCs:0.79-0.80,p=0.030). Conclusions: FIV-mRS discrepancies are associated with pre-treatment factors like age/comorbidities; and post-treatment complications related to stroke evolution, secondary prevention, and post-acute care quality. Optimizing thrombolysis speed, BP, glucose, and hemoglobin are modifiable factors meriting further study.

Background: Limbic encephalitis (LE) classically causes medial temporal lobe T2-hyperintensity on magnetic resonance imaging (MRI), but this can also occur with seizure activity. Identifying neuroimaging patterns that can distinguish between LE and seizure activity may help avoid diagnostic confusion in such challenging cases. Methods: Through retrospective review of Mayo Clinic patients who had medial temporal lobe T2-hyperintensity on MRI, we identified non-LE patients with seizure-related medial temporal lobe T2-hyperintensity. Their diffusion-weighted imaging (DWI) was reviewed to look for diffusion restriction patterns potentially unique to seizure activity. Next, a control cohort of LE patients with medial temporal lobe T2-hyperintensity was identified, and their DWI was reviewed to see if these diffusion restriction patterns could help distinguish seizure activity from LE. Results: We identified 10 non-LE patients who had medial temporal lobe T2-hyperintensity due to seizure activity; 9/10 had one of two medial temporal lobe diffusion restriction patterns we uncovered as being potentially unique to seizure activity. In contrast, only 5/57 LE patients had one of these diffusion restriction patterns identified, all of whom had seizures reported. Conclusions: We report two diffusion restriction patterns that may help distinguish seizure activity from LE. Recognition of these diffusion restriction patterns should prompt evaluation for possible seizure activity.

The AD 775 peak in Δ14C (henceforth, M12) was first measured by Miyake et al. and has since been confirmed globally. Here we present earlywood and latewood Δ14C values from tree rings of pinyon pine (Pinus edulis) from Mummy Cave, Canyon de Chelly National Monument, Chinle, Arizona, USA, for the period AD 770–780. These data reconfirm the timing of M12 and show a small rise in Δ14C in AD 774 latewood. Allowing for the delay in lateral transfer of radiocarbon produced at high latitude, this suggests that 14C peak production occurred in late winter or spring of AD 774. Additionally, Δ14C decreased slightly in the earlywood of AD 775 and increased in the latewood of AD 775 to a higher level than that observed in AD 774.

There is currently no simple and morbidity-free procedure available to determine opiate dependence in patients. There is preliminary evidence, however, that the naloxone conjunctival test may be useful in this regard. This test consists of instilling a drop of saline solution of naloxone hydrochloride (an opiate-receptor antagonist) into the subject's eye. This causes significant homolateral mydriasis (anisocoria) in the eye of a chronic opioid-dependent subject and not in that of a non-dependent subject. We reviewed the international literature on the naloxone conjunctival test using the Medline database and a manual search of major scientific journals specialized in the field of substance abuse. Up to March 1995, we identified six articles dealing specifically with the use of opiate antagonist ophthalmic solutions in populations of chronic opioid addicts. Four of the articles reported the occurrence of mydriasis when a solution of naloxone is used in opioid addicts. Two of the articles reported that there was no differential change in pupil size when the naloxone solution is used; however, one study used a much weaker and the other a much stronger solution of naloxone than reported in the other studies. From our review of the literature, it appears that the naloxone conjunctival test holds great promise as a simple and morbidity-free method of testing for chronic opioid addiction and, therefore, it should be studied further and its usage eventually developed.