Interspecific variation in non-breeding aggregation: a multi-colony tracking study of two sympatric seabirds

Migration is a widespread strategy for escaping unfavourable conditions during winter, but the extent to which populations that segregate during the breeding season aggregate during the non-breeding season is poorly understood. Low non-breeding season aggregation may be associated with higher likelihood of overlap with threats, but with fewer populations affected, whereas high aggregation may result in a lower probability of exposure to threats, but higher overall severity. We investigated non-breeding distributions and extent of population aggregation in 2 sympatrically breeding auks. We deployed geolocation-immersion loggers on common guillemots Uria aalge and razorbills Alca torda at 11 colonies around the northern UK and tracked their movements across 2 non-breeding seasons (2017-18 and 2018-19). Using 290 guillemot and 135 razorbill tracks, we mapped population distributions of each species and compared population aggregation during key periods of the non-breeding season (post-breeding moult and mid-winter), observing clear interspecific differences. Razorbills were largely distributed in the North Sea, whereas guillemot distributions were spread throughout Scottish coastal waters and the North, Norwegian and Barents Seas. We found high levels of aggregation in razorbills and a strong tendency for colony-specific distributions in guillemots. Therefore, razorbills are predicted to have a lower likelihood of exposure to marine threats, but more severe potential impact due to the larger number of colonies affected. This interspecific difference may result in divergent population trajectories, despite the species sharing protection at their breeding sites. We highlight the importance of taking whole-year distributions into account in spatial planning to adequately protect migratory species.</jats:p

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Gender and Literary Valorization: The Awakening of a Canonical Novel.” Sociological Perspectives 45(2):139–61

Kate Chopin&apos;s novel The Awakening was published on April 22, 1899. At that time, Chopin was a well-known resident of St. Louis, a widow who supported her six children through writing. Her career was increasingly successful; she had published her rst novel in 1890 and two successful collections of short stories, Bayou Folk and A Night in Acadie , in 1894 and 1897 respectively. Chopin had also published a large number of short stories, poems, and essays in both popular and literary magazines, including Youth&apos;s Companion and Vogue

Prevalence of heart disease in patients with mitochondrial abnormalities on skeletal muscle biopsy

Abstract Objective Mitochondrial DNA mutations are associated with an increased risk of heart disease. Whether an increased prevalence of cardiovascular disease is present in patients presenting with mitochondrial abnormalities on skeletal muscle biopsy remains unknown. This study was designed to determine the prevalence of cardiac conduction disease and structural heart disease in patients presenting with mitochondrial abnormalities on skeletal muscle biopsy. Methods This is a retrospective cohort study of 103 patients with mitochondrial abnormalities on skeletal muscle biopsy who were referred for evaluation of muscle weakness at a single tertiary care referral center from 2012 to 2018. Of these patients, 59 (57.3%) had an electrocardiogram available and were evaluated for the presence of conduction disease. An echocardiogram was available in 43 patients (42%) who were evaluated for the presence of structural heart disease. The prevalence of cardiac disease was compared to control cohort populations (Framingham and the Atherosclerosis Risk in Communities, ARIC cohorts). Results Mitochondrial abnormalities associated with cardiac conduction disease (defined as QRS duration ≥ 120 msec) were present in 8.9%, versus 2.0% (p < 0.001) in the Framingham population and 2.6% (p = 0.003) in the ARIC cohort. LV systolic dysfunction (LVEF ≤ 50%) was present in 11.6%, versus 3.6% (p < 0.01) in the Framingham and 3% (p < 0.01) in the ARIC populations. Left ventricular hypertrophy was present in 28.6%, versus 13.6% (p < 0.02) in the Framingham and 10.4% (p < 0.001) in the ARIC populations. Interpretation Given the increased prevalence of cardiovascular disease, patients with mitochondrial abnormalities on skeletal muscle biopsy should undergo routine cardiac screening with physical exam, electrocardiography, and cardiac imaging

The IRF4 Gene Regulatory Module Functions as a Read-Write Integrator to Dynamically Coordinate T&nbsp;Helper Cell Fate

Transcriptional regulation during CD4+ T&nbsp;cell fate decisions enables their differentiation into distinct states, guiding immune responses toward antibody production via Tfh cells or inflammation by Teff cells. Tfh-Teff cell fate commitment is regulated by mutual antagonism between the transcription factors Bcl6 and Blimp-1. Here we examined how T&nbsp;cell receptor (TCR) signals establish and arbitrate Bcl6-Blimp-1 counter-antagonism. We found that the TCR-signal-induced transcription factor Irf4 is essential for the differentiation of Bcl6-expressing Tfh and Blimp-1-expressing Teff cells. Increased TCR signaling raised Irf4 amounts and promoted Teff cell fates at the expense of Tfh ones. Importantly, orthogonal induction of Irf4 expression redirected Tfh cell fate trajectories toward those of Teff. Mechanistically, we linked greater Irf4 abundance with its recruitment toward low-affinity binding sites within Teff cell cis-regulatory elements, including those of Prdm1. We propose that the Irf4 locus functions as the "reader" of TCR signal strength, and in turn, concentration-dependent activity of Irf4 "writes" T helper fate choice