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.

Insulin-like growth factor 1 (IGF-1) is an important growth factor in childhood. We aimed to investigate the impact of food supplements for the treatment of moderate acute malnutrition (MAM) on serum IGF-1 (sIGF-1). Secondary analysis of a randomised 2 × 2 × 3 factorial nutrition trial was performed. Children aged 6–23 months with MAM received 2093 kJ/d as lipid-based nutrient supplement (LNS) or corn soy blend (CSB), containing either dehulled soya or soya isolate and different quantities of dried skimmed milk (0 %, 20 % or 50 % of total protein) for 12 weeks. The trial was double-blind with regard to soya and milk but not to matrix (LNS v. CSB). sIGF-1 was measured at inclusion and after 12 weeks of supplementation. Of 1609 children enrolled, 1455 (90 %) had sIGF-1 measured at both time points. During supplementation, sIGF-1 increased 6·7 (95 % CI 6·1, 7·3) ng/ml compared with an expected age-dependent decrease of 0·3 (95 % CI 0·2, 0·4) ng/ml. Children who received LNS v. CSB had a lower increase in sIGF-1 (–8 %, 95 % CI − 12, −3). The effect of LNS was partly attenuated when sIGF-1 was corrected for inflammation. Children who received soya isolate compared with dehulled soya had a higher increase in sIGF-1 (6 %, 95 % CI 1, 12). Milk content did not affect sIGF-1. Overall, sIGF-1 increased during supplementation. The lower increase with LNS v. CSB was only partly explained by increased inflammation with LNS and needs further investigation. Isolate v. dehulled soya led to a higher increase which may be due to antinutrients in dehulled soya.

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: 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.

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.

In Tanzania, there are high rates of suicidal thoughts and behavior among people living with HIV (PLWH), yet few instruments exist for effective screening and referral. To address this gap, we developed and validated Swahili translations of the Columbia Suicide Severity Rating Scale (C-SSRS) Screen Version and two accompanying scales assessing self-efficacy to avoid suicidal action and reasons for living. We administered a structured survey to 80 PLWH attending two HIV clinics in Moshi, Tanzania. Factor analysis of the items revealed four subscales: suicide intensity, self-efficacy to avoid suicide, fear and social concern about suicide, and family and spirituality deterrents to suicide. The area under the receiver operating curve showed only suicide intensity, and fear and social concern met the prespecified cutoff of ≥0.7 in accurately identifying patients with a plan and intent to act on suicidal thoughts. This study provides early evidence that brief screening of intensity of suicidality in the past month, assessed by the C-SSRS Screen Version, is a strong, resource-efficient strategy for identifying suicide risk in the Tanzanian setting. Patients who report little fear of dying and low concern about social perceptions of suicide may also be at increased risk.

The paper critically reexamines the well-known “Julie and Mark” vignette, a stylized account of two college-age siblings opting to engage in protected sex while vacationing abroad (e.g., Haidt, 2001). Since its inception, the story has been viewed as a rhetorically powerful validation of Hume’s “sentimentalist” dictum that moral judgments are not rationally deduced but arise directly from feelings of pleasure or displeasure (e.g., disgust). People’s typical reactions to the vignette are alleged to support this view by demonstrating that individuals are prone to become morally dumbfounded (Haidt, 2001; Haidt, Bjorklund, & Murphy, 2000), i.e., they tend to “stubbornly” maintain their disapproval of the act without supporting reasons. In what follows, we critically reassess the traditional account, predicated on the notion that, among other things, most subjects simply fail to be convinced that the siblings’ actions are truly harm-free, thus having excellent reasons to disapprove of these acts. In line with this critique, 3 studies found that subjects 1) tended not to believe that the siblings’ actions were in fact harmless; 2) notwithstanding that, and in spite of holding a number of “counterargument-immune” reasons, subjects could be effectively maneuvered into exhibiting all the trademark signs of a morally dumbfounded state (which they subsequently recanted), and 3) with subjects’ beliefs about harm and standards of normative evaluation properly factored in, a more rigorous assessment procedure yielded a dumbfounding estimate of about 0. Based on these and related results, we contend that subjects’ reactions are wholly in line with the rationalist model of moral judgment and that their use in support of claims of moral arationalism should be reevaluated.

We present the most sensitive and detailed view of the neutral hydrogen (${\rm H\small I}$) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ($1.6\,\mathrm{mJy\ beam}^{-1}$) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ (${\sim}10\,\mathrm{pc}$). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.

In this era of spatially resolved observations of planet-forming disks with Atacama Large Millimeter Array (ALMA) and large ground-based telescopes such as the Very Large Telescope (VLT), Keck, and Subaru, we still lack statistically relevant information on the quantity and composition of the material that is building the planets, such as the total disk gas mass, the ice content of dust, and the state of water in planetesimals. SPace Infrared telescope for Cosmology and Astrophysics (SPICA) is an infrared space mission concept developed jointly by Japan Aerospace Exploration Agency (JAXA) and European Space Agency (ESA) to address these questions. The key unique capabilities of SPICA that enable this research are (1) the wide spectral coverage $10{-}220\,\mu\mathrm{m}$, (2) the high line detection sensitivity of $(1{-}2) \times 10^{-19}\,\mathrm{W\,m}^{-2}$ with $R \sim 2\,000{-}5\,000$ in the far-IR (SAFARI), and $10^{-20}\,\mathrm{W\,m}^{-2}$ with $R \sim 29\,000$ in the mid-IR (SPICA Mid-infrared Instrument (SMI), spectrally resolving line profiles), (3) the high far-IR continuum sensitivity of 0.45 mJy (SAFARI), and (4) the observing efficiency for point source surveys. This paper details how mid- to far-IR infrared spectra will be unique in measuring the gas masses and water/ice content of disks and how these quantities evolve during the planet-forming period. These observations will clarify the crucial transition when disks exhaust their primordial gas and further planet formation requires secondary gas produced from planetesimals. The high spectral resolution mid-IR is also unique for determining the location of the snowline dividing the rocky and icy mass reservoirs within the disk and how the divide evolves during the build-up of planetary systems. Infrared spectroscopy (mid- to far-IR) of key solid-state bands is crucial for assessing whether extensive radial mixing, which is part of our Solar System history, is a general process occurring in most planetary systems and whether extrasolar planetesimals are similar to our Solar System comets/asteroids. We demonstrate that the SPICA mission concept would allow us to achieve the above ambitious science goals through large surveys of several hundred disks within $\sim\!2.5$ months of observing time.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

This paper investigates and questions the relevance of product-centric circularity indicators in a product design context. To do so, reviews of eco-design tools and critical analyses of circularity indicators at the micro level of circular economy implementation are combined with a new workshop experimenting four of these indicators with the aim to improve the circularity performance of an industrial product. On this basis, the four tool-based circularity indicators tested are mapped on the engineering design and development process, and are positioned among the pool of main eco-design tools.

Given the challenges in accurately identifying unexposed controls in case–control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within ‘control’ children (0–59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea (‘MSD pathogens’) in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and ‘any’ (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case–control studies examining diarrhoea.

Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.

Objectives: The present study examined the relative contribution of recent or long-term heading to neuropsychological function in amateur adult soccer players. Participants and Methods: Soccer players completed a baseline questionnaire (HeadCount-12m) to ascertain heading during the prior 12 months (long-term heading, LTH) and an online questionnaire (HeadCount-2w) every 3 months to ascertain heading during the prior 2 weeks (recent heading, RH). Cogstate, a battery of six neuropsychological tests, was administered to assess neuropsychological function. Generalized estimating equations were used to test if LTH or RH was associated with neuropsychological function while accounting for the role of recognized concussion. Results: A total of 311 soccer players completed 630 HeadCount-2w. Participants had an average age of 26 years. Participants headed the ball a median of 611 times/year (mean=1,384.03) and 9.50 times/2 weeks (mean=34.17). High levels of RH were significantly associated with reduced performance on a task of psychomotor speed (p=.02), while high levels of LTH were significantly associated with poorer performance on tasks of verbal learning (p=.03) and verbal memory (p=.04). Significantly better attention (p=.02) was detectable at moderately high levels of RH, but not at the highest level of RH. One hundred and seven (34.4%) participants reported a lifetime history of concussion, but this was not related to neuropsychological function and did not modify the association of RH or LTH with neuropsychological function. Conclusion: High levels of both RH and LTH were associated with poorer neuropsychological function, but on different domains. The clinical manifestations following repetitive exposure to heading could change with chronicity of exposure. (JINS, 2018, 24, 147–155)

Introduction: The social determinants of health (SDoH) can play a significant role in a person’s overall wellbeing. This is especially true for adults with mental illness and mental health disorders. In this study, we describe the SDoH of patients presenting to an academic, inner-city emergency department (ED) with an acute mental health complaint (AMHC). Methods: We prospectively identified and enrolled a convenience sample of patients presenting to an ED with an annual census of 85,000 visits. Participants provided informed written consent, and completed a questionnaire package containing questions related to demographics and SDoH. As well, participants were asked to complete four mental health, quality of life, and recovery validated patient-reported outcome measures. Results: A total 108 participants were enrolled in this study, of which 65% were male, aged 37.5 years (IQR 26.7-50.3), 56% Caucasian, and 22% Aboriginal. Depression was the primary diagnosis reported by 55% of participants, with 58.9% meeting the PhQ-9 cutoff for moderate-severe depression. The highest level of educational achievement for 44% of participants was high school or less, with 75% reporting being unemployed. Almost half (45%) reported engaging in less than two hours of structured activity each week. Thirty eight percent of participants reported living in their own apartment, with 25% reporting being homeless and 17% living in a single-room housing unit. The majority of participants (56%) sampled were not satisfied with their housing, and 67% were actively looking for new housing. Sixty percent of participants reported smoking cigarettes daily and 40% reported weekly cannabis use. A total of 11% of the sample reported that they did not have access to clean drinking water; 35% worried that their food would run out, and 47% reported cutting the size of meals due to a lack of money. Conclusion: This study lends evidence towards the circumstances in which patients presenting to the ED with an AMHC live and work. A considerable proportion of patients reported homelessness or being marginally housed, lack access to clean drinking water and sufficient food, and high rates of unemployment. Mitigating the effects of harmful social determinants is critical for optimal health of this population. Future work is needed to clarify the role of the ED in the surveillance, screening, and intervention of SDoH for this vulnerable patient group.

Introduction: In the last year, Canada published its Strategy for Patient-Oriented Research (SPOR) to ensure that patients receive the right treatment at the right time. Approximately, one in five Canadians will experience a mental illness in their life time, with many presenting to the Emergency Department (ED) as their entry point into the system. In order to improve patient outcomes and focus on patient-identified priorities, the aim of this study was to identify the short-term goals of patients with an acute mental health complaint (AMHC) presenting to the ED. Methods: We prospectively recruited a convenience sample of patients presenting to an inner city, academic ED with an annual census of 85,000 visits. Patients provided written informed consent and completed a survey package that included questions about employment intentions and short-term life goals. We collated the goals and used a content analysis to summarize the frequency of themes that emerged. Results: This study reports on the preliminary data from 108 of the targeted 200 patients (mean age 39.7 ±13.6 years; 65% male). A total of 75% of participants reported being unemployed, 84% of whom reported that they would like to gain some form of employment in the near future. Over half the sample (52%) identified that they were not satisfied with their current housing situation. In addition to improving housing and obtaining work, improving mental health (n=34), improving relationships with family or friends (n=27), going back to school (n=22) and managing addiction problems (n=20) were identified as the most common short-term goals. Other goals/priorities included improving physical health, traveling, exercising, and eating better. Conclusion: This study provides new information about the priorities of adults presenting with AMHC to the ED. It also offers insight into how to collaborate with patients to build sustainable, accessible, and coordinated care pathways that can bring about positive changes in their lives. This information can be used to compliment current care for mental health problems, ensuring greater quality, accountability, and continuity of care for this vulnerable patient group.