Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Evaluation du risque des brettanomyces non cultivables dans un vin rouge

At wine tastings doubts arise sometimes about the presence of volatil phenols, which are often the cause for barnyard, cloves, animal or stable odors. These odors are produced by Brettanomyces yeasts. Classic analysis methods include the counting of yeast cells after growth on agar medium. This analysis is not sufficient because Brettanomyces yeast may lose its ability to multiply all cells in response to stress but still remain viable. This viable but not cultivable (VNC) state is reversible. Tests were carried out in a red wine to find out if Brettanomyces yeasts, in the above mentioned state or exiting of it, retained their ability to produce volatile phenols. A stress factor of 30 mg/l free SO2 induced a VNC state. Brettanomyces yeasts lose the ability to degrade the wines but retrieve it as soon as the stress factor disappears and the yeast cells recover from their VNC state.Bei der Verkostung von Weinen entstehen manchmal Zweifel, ob flüchtige Phenole vorhanden sind, welche für Gerüche nach Reitstall, Gewürznelken, oder Stall oft verantwortlich sind. Diese Gerüche werden von Brettanomyces Hefen produziert. Die klassischen Analyse-Methoden beruhen auf der Auszählung der Hefen nach deren Vermehrung auf Agar. Diese Analysen reichen nicht aus, weil Brettanomyces Hefen ihre Fähigkeit, alle lebensfähigen Zellen zu vermehren, aufgrund einer Stressreaktion verlieren kann, obwohl sie lebensfähig bleiben. Dieser lebensfähige, nicht kultivierbare (VNC) Zustand ist umkehrbar. Versuche wurden in einem Rotwein durchgeführt, um zu prüfen, ob Brettanomyces Hefen im erwähnten oder aus ihm heraustretenden Zustand, ihre Fähigkeit behalten, flüchtige Phenole zu produzieren. Ein Stress von 30 mg/l freier SO2 induzierte den VNC-Zustand. Brettanomyces Hefen verlieren dabei ihre Fähigkeit, Weinfehler hervorzurufen, gewinnen diese Fähigkeit aber zurück, sobald der Stress verschwindet und sie aus dem VNC-Zustand heraustreten.Un dubbio appare talvolta alla degustazione dei vini sulla presenza di fenoli volatili responsabili di odori di scuderia, chiodi di garofano, cavallo. Questi odori sono prodotti del lievito Brettanomyces. I metodi di analisi classici passano dal conteggio dei lieviti dopo la crescita nell agar. Questo stato viabile non coltivabile (VNC) è reversibile. Dei test sono stati condotti nel vino rosso per verificare se in questo stato o uscendo da questo stato i Brettanomyces conservavano le loro capacità a produrre dei fenoli volatili. Uno stress di 30 mg/l di SO2 permette di indurre uno stato VCN. I Brettanomyces perdono allora la loro capacità di degradare i vini ma la ritrovano dal momento che lo stress sparisce e che escono da questo stato VCN

A new method of protein extraction from red wines

Aim: Wine is a very complex medium and is often evaluated according to its main components like alcohol, sugar, tannins, and acid levels. Proteins are rarely considered in this evaluation because their concentrations are only a few mg/L of wine. However, in an enological context, proteins appear to be more and more important, in particular for the stability of wines with protein haze problems. The study of proteins is less obvious in red wines than in white wines because the proteins are strongly tied to tannins, which makes their extraction and analysis even more difficult. Methods and results: This article describes a technique for the separation of proteins from tannins thanks to a methanol/chloroform emulsion in an acid solution. The protein extract, obtained after 4 hours, was later analyzed by SDS-Page and the protein profile of the wine established. Experiments showed that the protein profiles remained the same during the different stages of the winemaking process, whereas the overall amount of proteins decreased. Characteristic protein profiles of different grape varieties were established, and it was also possible to visualize the presence of exogenous proteins from fining agents like albumin and casein. Conclusion: This procedure allowed the extraction of proteins from 8 red wine samples within 4 hours. It also made it possible to analyze the extracted proteins by SDS-Page without tannin interference within 2 hours. Significance and impact of the study: This method shows in a very promising manner how proteins might be extracted from red wines after being separated from their tannins. The extracted proteins are then available for analysis using even more advanced techniques such as ESI-QTof or ELISA

Fruit pomace and waste frying oil as sustainable resources for the bioproduction of medium-chain-length polyhydroxyalkanoates

Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are biobased and biodegradable alternatives to petrol-derived polymers, whose break-through has been prevented by high production cost. Therefore we investigated whether wastes from the food industry (nine types of fruit pomace including apricots, cherries and grapes, and waste frying oil) could replace the costly sugars and fatty acids typically used as carbon substrates for the bacterial fermentations. A selection of enzyme preparations was tested for converting the residual polysaccharides from the pomaces into fermentable monosaccharides. From the pomace of apricots, cherries and Solaris grapes, 47, 49 and 106gL(-1) glucose were recovered, respectively. Solaris grapes had the highest sugar content whereas apricots contained the fewest growth inhibitors. These two pomaces were assessed for their suitability to produce mcl-PHA in bioreactor. A 2-step fermentation was established with Pseudomonas resinovorans, hydrolyzed pomace as growth substrate and WFO as mcl-PHA precursor. Solaris grapes proved to be a very promising growth substrate, resulting in the production of 21.3gPHA(Lpomace)(-1) compared to 1.4g PHA (L pomace)(-1) for apricots. Finally, capillary zone electrophoresis analyses allowed monitoring of sugar and organic acid uptake during the fermentation on apricots, which led to the discovery of reverse diauxie in P. resinovorans

Transforming knowledge systems for life on Earth : Visions of future systems and how to get there

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.Peer reviewe

Transforming knowledge systems for life on Earth: Visions of future systems and how to get there

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent