Market Research: Tenancy Fitout Material Procurement Attitudes and Practices

The Better Buildings partnership (BBP) has previously investigated the tenancy processes that generate waste successive cycles of fitout, de-fit, make good and re-fit. This research project has been commissioned to explore why waste occurs in commercial building fitouts and what can be done about it, with a particular focus on the materials that dominate the fitout waste stream. The characteristics of each material and aspects of its usage are explored to determine how to improve reuse and recycling rates. The Institute for Sustainable Futures (ISF) conducted in-depth interviews with 15 industry participants for this study, ranging from architects and property managers through to contractors and manufacturers. We also reviewed literature to provide context, however we found the available literature somewhat limited in terms of its currency, depth and local relevance. It is the interview conversations that provide a rich picture of the myriad issues and day-to-day problems that make it hard to institute a less wasteful, circular economy. The study attempts to place the problems in the context of the whole system to highlight possible solutions

Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia

OBJECTIVE: Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435). METHODS: Sixty-nine Friedreich ataxia patients were randomized 3:1 to either omaveloxolone or placebo administered once daily for 12 weeks. Patients were randomized in cohorts of eight patients, at dose levels of 2.5–300 mg/day. RESULTS: Omaveloxolone was well tolerated, and adverse events were generally mild. Optimal pharmacodynamic changes (noted by changes in ferritin and GGT) were observed at doses of 80 and 160 mg/day. No significant changes were observed in the primary outcome, peak work load in maximal exercise testing (0.9 ± 2.9 W, placebo corrected). At the 160 mg/day dose, omaveloxolone improved the secondary outcome of the mFARS by 3.8 points versus baseline (P = 0.0001) and by 2.3 points versus placebo (P = 0.06). Omaveloxolone produced greater improvements in mFARS in patients that did not have musculoskeletal foot deformity (pes cavus). In patients without this foot deformity, omaveloxolone improved mFARS by 6.0 points from baseline (P < 0.0001) and by 4.4 points versus placebo (P = 0.01) at the 160 mg/day. INTERPRETATION: Treatment of Friedreich ataxia patients with omaveloxolone at the optimal dose level of 160 mg/day appears to improve neurological function. Therefore, omaveloxolone treatment is being examined in greater detail at 150 mg/day for Friedreich ataxia

A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal

BACKGROUND: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. CONCLUSIONS/SIGNIFICANCE: A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01856205

SCAview: an Intuitive Visual Approach to the Integrative Analysis of Clinical Data in Spinocerebellar Ataxias

With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge

Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; A prospective observational study

Background: All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods. To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results: We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions: The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies. © 2013 Ashizawa et al.; licensee BioMed Central Ltd