Group augmentation underlies the evolution of complex sociality in the face of environmental instability.

Although kin selection is assumed to underlie the evolution of sociality, many vertebrates-including nearly half of all cooperatively breeding birds-form groups that also include unrelated individuals. Theory predicts that despite reducing kin structure, immigration of unrelated individuals into groups can provide direct, group augmentation benefits, particularly when offspring recruitment is insufficient for group persistence. Using population dynamic modeling and analysis of long-term data, we provide clear empirical evidence of group augmentation benefits favoring the evolution and maintenance of complex societies with low kin structure and multiple reproductives. We show that in the superb starling (Lamprotornis superbus)-a plural cooperative breeder that forms large groups with multiple breeding pairs, and related and unrelated nonbreeders of both sexes-offspring recruitment alone cannot prevent group extinction, especially in smaller groups. Further, smaller groups, which stand to benefit more from immigration, exhibit lower reproductive skew for immigrants, suggesting that reproductive opportunities as joining incentives lead to plural breeding. Yet, despite a greater likelihood of becoming a breeder in smaller groups, immigrants are more likely to join larger groups where they experience increased survivorship and greater reproductive success as breeders. Moreover, immigrants form additional breeding pairs, increasing future offspring recruitment into the group and guarding against complete reproductive failure in the face of environmental instability and high nest predation. Thus, plural breeding likely evolves because the benefits of group augmentation by immigrants generate a positive feedback loop that maintains societies with low and mixed kinship, large group sizes, and multiple reproductives.

Clinical spectrum of high-titre GAD65 antibodies.

OBJECTIVE: To determine clinical manifestations, immunotherapy responsiveness and outcomes of glutamic acid decarboxylase-65 (GAD65) neurological autoimmunity. METHODS: We identified 323 Mayo Clinic patients with high-titre (>20 nmol/L in serum) GAD65 antibodies out of 380 514 submitted anti-GAD65 samples (2003-2018). Patients classified as having GAD65 neurological autoimmunity after chart review were analysed to determine disease manifestations, immunotherapy responsiveness and predictors of poor outcome (modified Rankin score >2). RESULTS: On review, 108 patients were classified as not having GAD65 neurological autoimmunity and 3 patients had no more likely alternative diagnoses but atypical presentations (hyperkinetic movement disorders). Of remaining 212 patients with GAD65 neurological autoimmunity, median age at symptom onset was 46 years (range: 5-83 years); 163/212 (77%) were female. Stiff-person spectrum disorders (SPSD) (N=71), cerebellar ataxia (N=55), epilepsy (N=35) and limbic encephalitis (N=7) could occur either in isolation or as part of an overlap syndrome (N=44), and were designated core manifestations. Cognitive impairment (N=38), myelopathy (N=23) and brainstem dysfunction (N=22) were only reported as co-occurring phenomena, and were designated secondary manifestations. Sustained response to immunotherapy ranged from 5/20 (25%) in epilepsy to 32/44 (73%) in SPSD (p=0.002). Complete immunotherapy response occurred in 2/142 (1%). Cerebellar ataxia and serum GAD65 antibody titre >500 nmol/L predicted poor outcome. INTERPRETATION: High-titre GAD65 antibodies were suggestive of, but not pathognomonic for GAD65 neurological autoimmunity, which has discrete core and secondary manifestations. SPSD was most likely to respond to immunotherapy, while epilepsy was least immunotherapy responsive. Complete immunotherapy response was rare. Serum GAD65 antibody titre >500 nmol/L and cerebellar ataxia predicted poor outcome.

Prenatal environmental conditions underlie alternative reproductive tactics that drive the formation of a mixed-kin cooperative society.

Although animal societies often evolve due to limited natal dispersal that results in kin clustering and facilitates cooperation among relatives, many species form cooperative groups with low kin structure. These groups often comprise residents and immigrants of the same sex that compete for breeding opportunities. To understand how these mixed-kin societies form, we investigated the causes and fitness consequences of dispersal decisions in male cooperatively breeding superb starlings (Lamprotornis superbus) inhabiting a climatically unpredictable environment. We show that the two alternative reproductive tactics-natal dispersal or philopatry-exhibit reproductive trade-offs resulting in equivalent lifetime inclusive fitness. Unexpectedly, an individual's tactic is related to the prenatal environment its parents experience before laying rather than the environment it experiences as a juvenile. Individuals that adopt the tactic not predicted by prenatal environmental conditions have lower fitness. Ultimately, climate-driven oscillating selection appears to stabilize mixed-kin societies despite the potential for social conflict.

Frequency of Asymptomatic Optic Nerve Enhancement in a Large Retrospective Cohort of Patients With Aquaporin-4+ NMOSD.

BACKGROUND AND OBJECTIVES: Asymptomatic or persistent optic nerve enhancement in aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) is thought to be rare. Improved understanding may have important implications for assessment of treatment efficacy in clinical trials and in clinical practice. Our objective was to characterize NMOSD interattack optic nerve enhancement. METHODS: This was a retrospective cohort study performed between 2000 and 2019 (median follow-up 5.5 [range 1-35] years) of patients with AQP4-IgG-positive optic neuritis (ON) evaluated at Mayo Clinic. MRI orbits were reviewed by a neuroradiologist, neuro-ophthalmologist, and neuroimmunologist blinded to the clinical history. Interattack optic nerve enhancement (>30 days after attack) was measured. The correlation between interattack enhancement and Snellen visual acuity (VA), converted to logarithm of the minimum angle of resolution (logMAR), at attack and at follow-up were assessed. RESULTS: A total of 198 MRI scans in 100 patients with AQP4-IgG+ NMOSD were identified, with 107 interattack MRIs from 78 unique patients reviewed. Seven scans were performed before any ON (median 61 days before attack [range 21-271 days]) and 100 after ON (median 400 days after attack [33-4,623 days]). Optic nerve enhancement was present on 18/107 (16.8%) interattack scans (median 192.5 days from attack [33-2,943]) of patients with preceding ON. On 15 scans, enhancement occurred at the site of prior attacks; the lesion location was unchanged, but the lesion length was shorter. Two scans (1.8%) demonstrated new asymptomatic lesions (prior scan demonstrated no enhancement). In a third patient with subjective blurry vision, MRI showed enhancement preceding detectable eye abnormalities on examination noted 15 days later. There was no difference in VA at preceding attack nadir (logMAR VA 1.7 vs 2.1; p = 0.79) or long-term VA (logMAR VA 0.4 vs 0.2, p = 0.56) between those with and without interattack optic nerve enhancement. DISCUSSION: Asymptomatic optic nerve enhancement occurred in 17% of patients with NMOSD predominantly at the site of prior ON attacks and may represent intermittent blood-brain barrier breakdown or subclinical ON. New asymptomatic enhancement was seen only in 2% of patients. Therapeutic clinical trials for NMOSD require blinded relapse adjudication when assessing treatment efficacy, and it is important to recognize that asymptomatic optic nerve enhancement can occur in patients with ON.