Objective Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA. Methods We conducted an international, double‐blind, randomized, placebo‐controlled, parallel‐group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015‐002762‐23). Eligible patients, 16 to 40 years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks. Results One hundred fifty‐five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (−1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of –2.40 ± 0.96 ( p = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone. Interpretation In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ANN NEUROL 2021;89:212–225

ABSTRACT. Objective: This study examined how social-infl uence processes operate during specifi c drinking contexts as well as the stability and change in these processes throughout the college years. Method: Using a measurement-burst design, a hybrid of longitudinal and daily diary methods, we assessed the relationship between event-specifi c descriptive drinking norms and personal drinking. College students (N = 523) completed a baseline survey followed by a 30-day daily diary each year for up to the 4 study years. The baseline survey assessed participant gender and social anxiety, and the daily survey assessed personal drinking and perceived peer drinking (i.e., event-specifi c descriptive norms) during social drinking events. Results: Multilevel modeling revealed that men's social drinking slightly increased over the 4 years, whereas women's drinking remained steady. Further, on social drinking days when event-specifi c descriptive norms were high, students drank more, but this relationship was stronger for men than women and did not change over time. However, men's drinking norm perceptions increased across years, whereas women's decreased. Social anxiety did not moderate the relationship between norms and drinking. Conclusions: We demonstrate that although gender differences exist in the stability and change of personal drinking, norms, and normative infl uence on drinking across the years of college, the acute social infl uence of the norm on personal drinking remains a stable and important predictor of drinking throughout college. Our fi ndings can assist with the identifi cation of how, when, and for whom to target social infl uence-based interventions aimed at reducing drinking. (J. Stud. Alcohol Drugs, 72, 633-641, 2011)

Using experience sampling methods we examined how group size and context-specific drinking norms corresponded to alcohol consumption and compliance with drinking offers during natural social drinking events. For 30 days, 397 college students reported daily on their alcohol consumption during social events, the size of the group they were with, the average alcohol consumption of its’ members, and the number of drinks they accepted that came directly from the group they were with during these social drinking events. Larger groups corresponded with greater alcohol consumption, but only when context-specific norms were high. Furthermore, larger groups increased compliance with drinking offers when context-specific norms were high, but decreased compliance with drinking offers when context-specific norms were low. Thus, subtle features of the social-context may influence not only overall consumption behavior, but also compliance with more overt forms of social influence.

<b><i>Introduction:</i></b> Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (&#x3c;5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome. <b><i>Methods:</i></b> The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12–70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30–90 mL/min/1.73 m², and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values &#x3e;200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. <b><i>Results:</i></b> A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (<i>n</i> = 77) or placebo (<i>n</i> = 80). The average age at screening was 39.2 years, and 23 (15%) were &#x3c;18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m², and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was −4.9 mL/min/1.73 m² despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. <b><i>Discussion/Conclusion:</i></b> CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.

The objectives were to explore the relation between the built environment of residence halls and the alcohol use of college students living on campus from the perspective of the theory of routine activity. This exploratory study examined data from two samples on one college campus. Online surveys assessed alcohol use, attitudes toward alcohol use, perceptions of campus alcohol norms, and individual factors (i.e., gender). Data came from an Alcohol Norms Survey using a random sample ( N = 440) and a Resident Assessment Survey using a random sample ( N = 531) in 2006 and 2007. After controlling for other drinking behavior predictors (attitudes, gender, high school drinking, and perceptions of peer drinking), regression analysis showed that students living in suite halls had a higher odds of drinking more frequently, drinking more alcohol when they socialize, heavy episodic drinking, and drinking more often in their residence halls.