Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.

Background: Attitudes toward aging influence many health outcomes, yet their relationship with cognition and Alzheimer’s disease (AD) remains unknown. To better understand their impact on cognition and AD risk, we examined whether positive attitudes predict better cognition and diminished risk on AD biomarkers. Methods: A subsample of older adults with a family history of AD (n=54; women=39) from the McGill PREVENT-AD cohort participated in this study. Participants completed the Attitudes to Ageing Questionnaire (AAQ-24), providing three scores: psychosocial loss, psychological growth and physical change. Participants underwent cognitive testing (Rey Auditory Verbal Learning Test, RAVLT; Delis-Kaplan Executive Function System-Color Word Interference Test, D-KEFS-CWIT), and AD blood-based biomarker assessments (p-tau217, Aβ42/40). Regression models tested associations, adjusting for covariates (age, sex, education, depression, APOE4), and were Bonferroni corrected. Results: Positive attitudes were associated with better recall and recognition (RAVLT) and improved word reading, colour naming, switching, and inhibition (D-KEFS-CWIT) (p<0.00077), while negative attitudes showed the opposite pattern. Negative attitudes were correlated with lower Aβ42/40 ratios, while positive attitudes were linked to lower p-tau217 (p<0.0167). Conclusions: These findings demonstrate that positive attitudes predict better cognition and a lower risk profile for AD biomarkers, suggesting that life outlook may be an early disease feature or a risk factor.

Nearly half of all Australians (42.9%) will experience a mental health disorder during their lifetime(1). Preliminary research suggests an association between dietary and tissue advanced glycation end-products (AGEs) and mental health conditions, such as depression(2,3). However, more research is needed to determine the extent to which poor mental health is linked with AGEs(4). This study examined whether dietary consumption of the AGE carboxymethyl-lysine (CML), tissue accumulation of AGEs, or levels of circulating glycated haemoglobin (HbA1c) were associated with depression or anxiety. Fifty adults participated in a cross-sectional study. Depression and anxiety were assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D) and Spielberger’s State-Trait Anxiety Inventory (STAI). Dietary CML intake was assessed from 3-day food records by matching food items to those in published, validated food AGE databases and adjusting for energy intake (CML/MJ). Tissue accumulation of AGEs was measured as skin autofluorescence (SAF) using an AGE Reader. HbA1c was measured in whole blood using a Capillary 3 HbA1c kit. Spearman’s rank correlations were performed to explore relationships between variables. Participants included 14 males and 36 females, aged (median (range)) 30.6 (18–72) years. Participants were predominantly healthy, with a BMI of 23.3 (18.5–31.1) kg/m2 and energy intake of 7889 (5452–12568) kJ/day. Depression scores were 8 (0–40) out of 60. State anxiety scores were 26 (20–53) and trait anxiety scores were 33.5 (20–66) out of 80, where higher scores indicated greater symptom severity. Daily intake of CML was 0.6 (0.2–1.9) mg/MJ/day. SAF was 1.8 (1.2–3.3) arbitrary units (AU), similar to previously reported normal reference values(5). Circulating HbA1c was 5.1% (4.4–6.2%), all within the healthy range(6). Spearman’s correlation tests indicated no significant associations between any of the independent variables (CML/MJ, SAF, HbA1c) and any of the dependent variables (CES-D, STAI) (all p > 0.05). In this population of predominantly of healthy individuals, there was no association between dietary CML intake, tissue AGE accumulation or circulating HbA1c and increased symptom severity for depression or anxiety. The next step of this research is to investigate metabolomic markers in this population and their association with depression and anxiety. In relatively healthy people, dietary metabolites may be more sensitive to uncover whether a relationship exists between AGEs and depression and anxiety.

To meet the specific education needs of ethics committee members (primarily full-time healthcare professionals), the Regional Ethics Department of Kaiser Permanente Northern California (KPNCAL) and Washington State University’s Elson Floyd School of Medicine have partnered to create a one-academic year Medical Ethics Certificate Program. The mission-driven nature of the KPNCAL-WSU’s Certificate Program was designed to be a low-cost, high-quality option for busy full-time practitioners who may not otherwise opt to pursue additional education.

This article discusses the specific competency-focused methodologies and pedagogies adopted, as well as how the Certificate Program made permanent changes in response to the global pandemic. This article also discusses in detail one of the Program’s signature features, its Practicum—an extensive simulated clinical ethics consultation placing students in the role of ethics consultant, facilitating a conflict between family members played by paid professional actors. This article concludes with survey data responses from Program alumni gathered as part of a quality study.

Arrays of heaving buoy type wave energy converters (WECs) are a promising contender to harness the renewable power of ocean waves on a commercial scale but require strategies to achieve efficient capture of wave energy over broad frequency bands for economic viability. A WEC-array design is proposed for absorption over a target frequency range in the two-dimensional water wave context by spatially grading the resonant properties of WECs via linear spring–damper power take-off mechanisms. The design is based on theories for rainbow reflection and rainbow absorption, which incorporate analyses based on Bloch wave modes and pole–zero pairs in complex frequency space. In contrast to previous applications of these theories, the influence of a higher-order passband and associated pole–zero pairs are shown to influence absorption at the high-frequency end of the target interval. The theories are used to inform initialisations for optimisation algorithms, and an optimised array of only five WECs is shown to give near-perfect absorption ($\geq$99 %) over the target interval. Broadband absorption is demonstrated when surge and pitch motions are released, for irregular sea states, and for incident wave packets in the time domain, where the time-domain responses are decomposed into Bloch modes to connect with the underlying theory.

Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.

A variational principle is proposed to derive the governing equations for the problem of ocean wave interactions with a floating ice shelf, where the ice shelf is modelled by the full linear equations of elasticity and has an Archimedean draught. The variational principle is used to form a thin-plate approximation for the ice shelf, which includes water–ice coupling at the shelf front and extensional waves in the shelf, in contrast to the benchmark thin-plate approximation for ocean wave interactions with an ice shelf. The thin-plate approximation is combined with a single-mode approximation in the water, where the vertical motion is constrained to the eigenfunction that supports propagating waves. The new terms in the approximation are shown to have a major impact on predictions of ice shelf strains for wave periods in the swell regime.

The term “blue justice” was coined in 2018 during the 3rd World Small-Scale Fisheries Congress. Since then, academic engagement with the concept has grown rapidly. This article reviews 5 years of blue justice scholarship and synthesizes some of the key perspectives, developments, and gaps. We then connect this literature to wider relevant debates by reviewing two key areas of research – first on blue injustices and second on grassroots resistance to these injustices. Much of the early scholarship on blue justice focused on injustices experienced by small-scale fishers in the context of the blue economy. In contrast, more recent writing and the empirical cases reviewed here suggest that intersecting forms of oppression render certain coastal individuals and groups vulnerable to blue injustices. These developments signal an expansion of the blue justice literature to a broader set of affected groups and underlying causes of injustice. Our review also suggests that while grassroots resistance efforts led by coastal communities have successfully stopped unfair exposure to environmental harms, preserved their livelihoods and ways of life, defended their culture and customary rights, renegotiated power distributions, and proposed alternative futures, these efforts have been underemphasized in the blue justice scholarship, and from marine and coastal literature more broadly. We conclude with some suggestions for understanding and supporting blue justice now and into the future.

The paper presents the method and findings of a Delphi expert survey to assess the impact of UK government farm animal welfare policy, farm assurance schemes and major food retailer specifications on the welfare of animals on farms. Two case-study livestock production systems are considered, dairy and cage egg production. The method identifies how well the various standards perform in terms of their effects on a number of key farm animal welfare variables, and provides estimates of the impact of the three types of standard on the welfare of animals on farms, taking account of producer compliance. The study highlights that there remains considerable scope for government policy, together with farm assurance schemes, to improve the welfare of farm animals by introducing standards that address key factors affecting animal welfare and by increasing compliance of livestock producers. There is a need for more comprehensive, regular and random surveys of on-farm welfare to monitor compliance with welfare standards (legislation and welfare codes) and the welfare of farm animals over time, and a need to collect farm data on the costs of compliance with standards.

Extensions of Rayleigh–Bloch waves above the cutoff frequency are studied via the discrete spectrum of a transfer operator for a channel containing a single cylinder with quasi-periodic side-wall conditions. Above the cutoff, the Rayleigh–Bloch wavenumber becomes complex valued and an additional wavenumber appears. For small- to intermediate-radius values, the extended Rayleigh–Bloch waves are shown to connect the Neumann and Dirichlet trapped modes before embedding in the continuous spectrum. A homotopy method involving an artificial damping term is proposed to identify the discrete spectrum close to the embedding. Moreover, Rayleigh–Bloch waves vanish beyond some frequency but reappear at higher frequencies for small and large cylinders. The existence and properties of the Rayleigh–Bloch waves are connected with finite-array resonances.