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Objectives Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. Methods Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤−1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. Results A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. Conclusion AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Exploring who, what and how we remember, this piece proposes that to remember requires, on the one hand, an auto-memoration (the means by which we remember ourselves, and therefore how we shape and present ourselves to others), and at the same time, on the other hand, auto-memoration always detours through the world and through the other, which requires ‘con-memoration’ (remembering with the other). Referring to Derrida and Nancy, this piece argues that the memories of ourselves, and of others, is always already mediated because structured by differance and the other, and thus entails also a forgetting.

Background The evaluation of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive test (CAT) in adults with systemic lupus erythematous (SLE) is an emerging field of research. We aimed to examine the test–retest reliability and construct validity of the PROMIS CAT in a Canadian cohort of patients with SLE. Methods Two hundred twenty-seven patients completed 14 domains of PROMIS CAT and seven legacy instruments during their clinical visits. Test–retest reliability of PROMIS was evaluated 7–10 days from baseline using intraclass correlation coefficient (ICC (2; 1)). The construct validity of the PROMIS CAT domains was evaluated against the commonly used legacy instruments, and also in comparison to disease activity and disease damage using Spearman correlations. A multitrait-multimethod matrix (MMM) approach was used to further assess construct validity comparing selected 10 domains of PROMIS and SF-36 domains. Results Moderate to excellent reliability was found for all domains (ICC [2;1] ranging from lowest, 0.66 for Sleep Disturbance and highest, 0.93 for the Mobility domain). Comparing seven legacy instruments with 14 domains of PROMIS CAT, moderate to strong correlations (0.51–0.91) were identified. The average time to complete all PROMIS CAT domains was 11.7 min. The MMM further established construct validity by showing moderate to strong correlations (0.55–0.87) between select PROMIS and SF-36 domains; the average correlations from similar traits (convergent validity) were significantly greater than the average correlations from different traits. Conclusions These results provide evidence on the reliability and validity of PROMIS CAT in SLE in a Canadian cohort.

Glucocorticoids are regulated by the hypothalamic-pituitary-adrenal (HPA) axis and are important in responding to various psychological and physiological stressors. For the African wild dog (

From US President Donald Trump’s Tweet labeling news media “the enemy of the people” to Hungarian Prime Minister Viktor Orbán’s establishment of a politically appointed Media Authority, media freedom is under threat in democracies and nondemocracies alike. According to Freedom House, in 2016 media freedom declined globally to its lowest level since 2003, with Europe experiencing the largest regional decrease. We investigate the relationship between government and media in Hungary and Poland and develop a theory that the rise of nationalist sentiment and leaders who leverage this sentiment to encourage censorship from the bottom-up has led to increased media restrictions from the top-down. We posit that bottom-up censorship will erode media credibility and make people more accepting of top-down media restrictions, which could, in turn, lead to nationalism unchecked by the fourth estate. Using a multilevel analysis of World Values Survey, we analyze the relationship between nationalism and media distrust. Using a cross-national time series, we analyze the relationship between nationalist sentiment and media restrictions. We find that increased nationalism is indeed associated with media distrust and media restrictions.

Chikungunya virus (CHIKV) has re-emerged as a significant human pathogen in the 21st century, causing periodic, and sometimes widespread, outbreaks over the past 15 years. Although mortality is very rare, a debilitating arthralgia is very common and may persist for months or years. There are no antivirals that are approved for the treatment of CHIKV infection, and current treatment options consist of supportive care only. Herein, we demonstrate the efficacy of a CHIKV-specific antibody in the prophylactic and therapeutic treatment of CHIKV in mouse models of disease. The fully human anti-CHIKV monoclonal Ab SVIR023 demonstrated broad in vitro activity against representative strains from the three major CHIKV clades. Therapeutic treatment with SVIR023 administered 1- or 3-days post-infection resulted in reduced virus in various tissues in a dose- and time-dependent manner. Prophylactic treatment up to 4 weeks prior to virus challenge was also effective in preventing disease in mice. Mice treated with SVIR023 and infected with CHIKV were resistant to secondary challenge and no evidence of antibody enhancement of disease was observed. Treatment with SVIR023 was effective in mouse models of CHIKV infection and disease and further evaluation towards clinical development is warranted.

Refereed/Peer-reviewed Embodied energy has a significant effect on the total environmental impact of a project. However, emphasis is often placed primarily on operational energy, resulting in a knowledge gap about the current state of embodied energy use in affordable housing. To address this, the study investigates the level of embodied energy consumption in affordable housing, as well as the drivers, barriers, and techniques to reduce embodied energy. Based on a single embedded case study covering the period from cradle to end of construction, data were collected using embodied energy calculations of three affordable housing units in the project, semi-structured interviews with five design team members, and a cross-examination of findings with contract documents. The results were analysed using sensitivity analysis and thematic analysis. The findings revealed that all three house units fulfilled the baseline embodied carbon target of 800 kg CO2 /m2 and both detached properties fell within the LETI (2020) target of 500 kg CO2 /m2 . However, all three properties would fail to meet the RIBA or 2030 LETI target of 300 kg CO2 /m2 . This suggests that improvements are necessary to achieve future targets. The results show that financial capabilities and operational energy prioritisation act as the main enabler and barrier for reducing embodied energy. Local contractors/suppliers, minimising material use or intensity, and modular construction were highlighted as the key reduction techniques that can be used to help achieve future targets concerning embodied carbon in residential developments. The study contributes significantly to understanding the current state of embodied energy use in affordable housing and provides new insights on how to deal with embodied energy if we are to meet future energy targets.

ObjectivesThis study aimed to evaluate the prevalence and incidence of herpes zoster (HZ) events and describe its associated factors in a study of patients with SLE.Methods491 consecutive SLE participants were screened for HZ events using a patient-reported questionnaire to capture outcomes on pain and other characteristics associated with HZ events. Sociodemographic, clinical and laboratory measures were also analysed, and time-dependent Cox regression survival analyses were performed to investigate factors associated with HZ events.ResultsPrevalence of HZ was 30.5%, incidence was 14.3 cases per 1000 person-years. Lymphopenia and glucocorticoid dosing were significantly associated with HZ events.ConclusionsHZ is highly prevalent in SLE, which may be linked to disease-related and treatment-related effects on cellular immunity. Our results suggest that the presence of certain risk factors may be useful to allow identification of patients at risk of HZ and improve its management in patients with SLE.

Objective We previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM’s concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis. Methods 300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM’s criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs. Results Two models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results. Conclusion We provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

One of Derrida’s deconstructive moves is to expose the contingency and contextuality of the structural, and hence political, relations between concepts. He particularly brings together what seems to be unrelated concepts (animals, death, sovereignty, language, and so on), to reveal how, throughout the history of philosophy, conceptual structures shape and constitute the human subject as ipseity. One such concept is friendship. This chapter argues that for Derrida the philosophical-historical concept of friendship serves to preserve and protect what is considered, since Aristotle, to be proper to “man”, in opposition to what is not proper to “man”, for example, the animal. Developing the play of symmetry and dissymmetry as they structure relations of friendship between humans but also between humans and nonhumans, the chapter uses the latter to explore our absolute responsibility for the other and subsequently reflects on the place of the animal in “democracy to come”. How might the inclusion of the animal other as friend “break all ipseity apart in advance”.

The purpose of the current study was to create a dynamic cadaveric shoulder model to determine the effect of graft fixation angle on shoulder biomechanics following SCR and to assess which commonly used fixation angle (30° vs 45° of abduction) results in superior glenohumeral biomechanics.Twelve fresh-frozen cadaveric shoulders were evaluated using a dynamic shoulder testing system. Humeral head translation, subacromial and glenohumeral contact pressures were compared among 4 conditions: (1) Intact, (2) Irreparable supra- and infraspinatus tendon tear, (3) SCR using acellular dermal allograft (ADA) fixation at 30° of abduction, and (4) SCR with ADA fixation at 45° of abduction.SCR at both 30° (0.287 mm, CL: -0.480 - 1.05 mm, p.0001) and 45° (0.528 mm, CL: -0.239-1.305 mm, p=0.0006) significantly decreased superior translation compared to the irreparably torn state. No significant changes in subacromial peak contact pressure were observed between any states. The average glenohumeral contact pressure increased significantly following creation of an irreparable RCT (373 kPa, CL: 304-443 versus 283 kPa, CL 214-352; p = 0.0147). The SCR performed at 45° (295 kPa, CL: 226-365, p=0.0394) of abduction significantly decreased the average glenohumeral contact pressure compared to the RCT state. There was no statistically significant difference between the average glenohumeral contact pressure of the intact state and SCR at 30° and 45°.SCR improved the superior stability of the glenohumeral joint when the graft was secured at 30° or 45° of glenohumeral abduction. Fixation at 45° of glenohumeral abduction provided more stability than did fixation at 30°.Grafts attached at 45° of glenohumeral abduction biomechanically restore the glenohumeral stability after SCR using ADA better than fixation at 30° of glenohumeral abduction.

We are studying the use of peer-to-peer group intervention as a means of promoting older adult health self-efficacy and self-management. To explore how older adults have worked together to improve health behaviors, a scoping review was conducted of older adult peer coaching in health maintenance or health improvement groups. Seventeen studies met all search criteria, including interventions examining the value of peer support in self-management of diabetes, a peer led program for fear of falling, and the effect of self-help groups on quality of life. Two models of peer engagement were identified: peer support and mutually supportive environments. Ten studies trained older adults to be peer mentors or leaders with training periods varying from two days to 30 weeks, although many did not include details of the training. The other seven studies examined mutually supportive environments for peer engagement such as a clinician-led with peer-support model, an app-based program with a social support component, and a prevention focused mutual support group. These studies included research comparing self-care and quality of life results after self-help group therapy and a study that analyzed the impact and role of volunteering at a seniors’ centre on maximizing member self-efficacy. While all studies reported on peer self-health engagement, there were many different goals ranging from evaluating health improvement programs to comparing peer and professional health group leadership. One consistent theme was improved perceived self-efficacy though peer group engagement.

Background: Modifiable lifestyle behaviours can reduce dementia risk by 40%, but their prevalence and association with cognition throughout the adult lifespan is less well understood. Methods: Associations between eight modifiable risk factors for dementia (low education, hypertension, hearing loss, traumatic brain injury, alcohol or substance abuse, diabetes, smoking, and depression) and cognition were examined in an online sample (N = 22,117, aged 18-89). Findings: Older adults (ages 66-89) had more risk factors than middle-aged (ages 45-65) and younger adults (ages 18-44). Polynomial regression revealed each additional risk factor was associated with a drop in cognitive performance (equivalent to three years of aging), with a larger association as age increased. People with no risk factors in their forties to seventies showed similar cognitive performance to people ten or twenty years younger with many risk factors. Interpretation: Modifiable dementia risk factors may be more important than age in predicting cognitive performance.

A common assumption regarding media freedom is that free media will hold government accountable and improve citizens’ lives. The assumption is that media will report any repression, thereby...

Objective A recent study conducted by our clinical group demonstrated that low disease activity (LDA), defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤2, maintained for 12 months, confers the same risk for damage accrual as complete remission after 2 years. The aim of the present study was to assess the validity of these findings in the long term (10 years). Methods Patients in the inception cohort of the Toronto Lupus Clinic, who had a minimum follow-up of 10 years and no interval >18 months between consecutive visits, were included in the analysis. Prolonged clinical remission was defined based on a SLEDAI-2K score of 0 (serology excluded), achieved within the first 5 years of enrollment and maintained for ≥10 years. Prolonged LDA was defined as SLEDAI-2K score ≤2 (serology excluded) with the same time frame restrictions. Results Of 267 patients, 27 (10.1%) achieved prolonged clinical remission and 48 (18%) attained prolonged LDA. There were no differences regarding demographic, clinical, and immunologic variables at any time. The mean prednisone dose at enrollment was higher in patients in whom remission was achieved, while patients with prolonged LDA were taking antimalarials more frequently, both at enrollment and after the 10-year time period. Cumulative damage and flare rate after 10 years, and mortality throughout follow-up were comparable. SLE in patients in the prolonged LDA group was in complete remission for 76% of the follow-up time. Conclusion Prolonged clinical remission and LDA were demonstrated in 10.1% and 18% of our patients, respectively, and comparable outcomes were demonstrated in the long term, rendering sustained LDA an acceptable treat-to-target outcome in SLE.

Subscapularis (SSC) tendon tears are less common than tears of the remaining rotator cuff tendons, but one with serious consequences given its function as one of the main internal rotators and anterior stabilizers. Mild fraying involving the upper third of the tendon can be treated non-operatively; however, more substantive tears usually require repair in cases of pain or functional impairment. Given the importance of the subscapularis tendon in maintaining stability of the glenohumeral joint and performing internal rotation of the arm, surgical intervention with emphasis on repair may be recommended to eliminate pain and restore strength. Postoperative rehabilitation through phased progression is utilized to avoid premature stress on the healing tissue while enabling early return to daily activities. The purpose of this clinical commentary is to provide an evidence-based description of postoperative rehabilitation following SSC tendon repair with guidance for safe and effective return to activity and sports. Level of evidence 5.

Several arenaviruses, including Lassa and Lujo viruses in Africa and five New World arenavirus (NWA) species in the Americas, cause life-threatening viral hemorrhagic fevers. In the absence of licensed antiviral therapies, these viruses pose a significant public health risk. The envelope glycoprotein complex (GPC) mediates arenavirus entry through a pH-dependent fusion of the viral and host endosomal membranes. It thus is recognized as a viable target for small-molecule fusion inhibitors. Here, we report on the antiviral activity and pre-clinical development of the novel broad-spectrum arenavirus fusion inhibitors, ARN-75039 and ARN-75041. In Tacaribe virus (TCRV) pseudotyped and native virus assays, the ARN compounds were active in the low to sub-nanomolar range with selectivity indices exceeding 1000. Pharmacokinetic analysis of the orally administered compounds revealed an extended half-life in mice supporting once-daily dosing, and the compounds were well tolerated at the highest tested dose of 100 mg/kg. In a proof-of-concept prophylactic efficacy study, doses of 10 and 35 mg/kg of either compound dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues. Additionally, in contrast to surviving mice that received ribavirin or placebo, animals treated with ARN-75039 or ARN-75041 were cured of TCRV infection. In a follow-up study with ARN-75039, impressive therapeutic efficacy was demonstrated under conditions where treatment was withheld until after the onset of disease. Taken together, the data strongly support the continued development of ARN-75039 as a candidate therapeutic for the treatment of severe arenaviral diseases.

Background: Healthy diet and exercise are associated with reduced risk of dementia in older adults. Evidence for the impact of clinical trials on brain health is less consistent, especially with dietary interventions which often rely on varying intervention approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counselling approach among older adults with vascular risk factors (VRFs) and early dementia risk. Methods: Participants with VRF’s and SCD or early MCI were cluster randomized into the intervention (exercise + Baycrest Brain-healthy Eating Approach (EX+DIET)) or control group (exercise + brain health education (EX+ED)). Both groups participated in 1-hour of supervised exercise per week and were prescribed additional exercise at home. EX+DIET involved 1-hour per week of group-based dietary counselling comprising didactic education focused on brain healthy eating recommendations, goal setting and strategy training. Whereas, EX+ED involved 1-hour per week of group-based brain health education. The primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included fitness, diet, cognition, and blood biomarkers. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. Results: Of 190 older adults contacted, 14 (7%) were eligible and randomized, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and diet/education sessions on average. All 6-month follow-up assessments pre-COVID-19 were completed but disruptions to testing during the pandemic resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the intervention. Mean improvements in peak oxygen consumption were observed in both EX+DIET (d = .98) and EX+ED (d =1.15) groups. Substantial improvements in diet and HbA1c were observed in the EX+DIET group compared to EX+ED (d = 1.75 and 1.07, respectively). Conclusions: High adherence and retention rates were observed among LEAD participants and preliminary findings illustrate improvements in cardiorespiratory fitness and diet quality. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. Trial Registration: ClinicalTrials.gov identifier: NCT03056508