Follow-up of phase I trial of adalimumab and rosiglitazone in FSGS: III. Report of the FONT study group

Abstract Background Patients with resistant primary focal segmental glomerulosclerosis (FSGS) are at high risk of progression to chronic kidney disease stage V. Antifibrotic agents may slow or halt this process. We present outcomes of follow-up after a Phase I trial of adalimumab and rosiglitazone, antifibrotic drugs tested in the Novel Therapies in Resistant FSGS (FONT) study. Methods 21 patients -- 12 males and 9 females, age 16.0 ± 7.5 yr, and estimated GFR (GFRe) 121 ± 56 mL/min/1.73 m2 -- received adalimumab (n = 10), 24 mg/m2 every 14 days or rosiglitazone (n = 11), 3 mg/m2 per day for 16 weeks. The change in GFRe per month prior to entry and after completion of the Phase I trial was compared. Results 19 patients completed the 16-week FONT treatment phase. The observation period pre-FONT was 18.3 ± 10.2 months and 16.1 ± 5.7 months after the study. A similar percentage of patients, 71% and 56%, in the rosiglitazone and adalimumab cohorts, respectively, had stabilization in GFRe, defined as a reduced negative slope of the line plotting GFRe versus time without requiring renal replacement therapy after completion of the FONT treatment period (P = 0.63). Conclusion Nearly 50% of patients with resistant FSGS who receive novel antifibrotic agents may have a legacy effect with delayed deterioration in kidney function after completion of therapy. Based on this proof-of-concept preliminary study, we recommend long-term follow-up of patients enrolled in clinical trials to ascertain a more comprehensive assessment of the efficacy of experimental treatments

Biorefining of wheat straw:accounting for the distribution of mineral elements in pretreated biomass by an extended pretreatment–severity equation

BACKGROUND: Mineral elements present in lignocellulosic biomass feedstocks may accumulate in biorefinery process streams and cause technological problems, or alternatively can be reaped for value addition. A better understanding of the distribution of minerals in biomass in response to pretreatment factors is therefore important in relation to development of new biorefinery processes. The objective of the present study was to examine the levels of mineral elements in pretreated wheat straw in response to systematic variations in the hydrothermal pretreatment parameters (pH, temperature, and treatment time), and to assess whether it is possible to model mineral levels in the pretreated fiber fraction. RESULTS: Principal component analysis of the wheat straw biomass constituents, including mineral elements, showed that the recovered levels of wheat straw constituents after different hydrothermal pretreatments could be divided into two groups: 1) Phosphorus, magnesium, potassium, manganese, zinc, and calcium correlated with xylose and arabinose (that is, hemicellulose), and levels of these constituents present in the fiber fraction after pretreatment varied depending on the pretreatment-severity; and 2) Silicon, iron, copper, aluminum correlated with lignin and cellulose levels, but the levels of these constituents showed no severity-dependent trends. For the first group, an expanded pretreatment-severity equation, containing a specific factor for each constituent, accounting for variability due to pretreatment pH, was developed. Using this equation, the mineral levels could be predicted with R(2) > 0.75; for some with R(2) up to 0.96. CONCLUSION: Pretreatment conditions, especially pH, significantly influenced the levels of phosphorus, magnesium, potassium, manganese, zinc, and calcium in the resulting fiber fractions. A new expanded pretreatment-severity equation is proposed to model and predict mineral composition in pretreated wheat straw biomass

Toward an improved representation of middle atmospheric dynamics thanks to the ARISE project

This paper reviews recent progress toward understanding the dynamics of the middle atmosphere in the framework of the Atmospheric Dynamics Research InfraStructure in Europe (ARISE) initiative. The middle atmosphere, integrating the stratosphere and mesosphere, is a crucial region which influences tropospheric weather and climate. Enhancing the understanding of middle atmosphere dynamics requires improved measurement of the propagation and breaking of planetary and gravity waves originating in the lowest levels of the atmosphere. Inter-comparison studies have shown large discrepancies between observations and models, especially during unresolved disturbances such as sudden stratospheric warmings for which model accuracy is poorer due to a lack of observational constraints. Correctly predicting the variability of the middle atmosphere can lead to improvements in tropospheric weather forecasts on timescales of weeks to season. The ARISE project integrates different station networks providing observations from ground to the lower thermosphere, including the infrasound system developed for the Comprehensive Nuclear-Test-Ban Treaty verification, the Lidar Network for the Detection of Atmospheric Composition Change, complementary meteor radars, wind radiometers, ionospheric sounders and satellites. This paper presents several examples which show how multi-instrument observations can provide a better description of the vertical dynamics structure of the middle atmosphere, especially during large disturbances such as gravity waves activity and stratospheric warming events. The paper then demonstrates the interest of ARISE data in data assimilation for weather forecasting and re-analyzes the determination of dynamics evolution with climate change and the monitoring of atmospheric extreme events which have an atmospheric signature, such as thunderstorms or volcanic eruptions

Challenge clusters facing LCA in environmental decision-making—what we can learn from biofuels

Purpose Bioenergy is increasingly used to help meet greenhouse gas (GHG) and renewable energy targets. However, bioenergy’s sustainability has been questioned, resulting in increasing use of life cycle assessment (LCA). Bioenergy systems are global and complex, and market forces can result in significant changes, relevant to LCA and policy. The goal of this paper is to illustrate the complexities associated with LCA, with particular focus on bioenergy and associated policy development, so that its use can more effectively inform policymakers. Methods The review is based on the results from a series of workshops focused on bioenergy life cycle assessment. Expert submissions were compiled and categorized within the first two workshops. Over 100 issues emerged. Accounting for redundancies and close similarities in the list, this reduced to around 60 challenges, many of which are deeply interrelated. Some of these issues were then explored further at a policyfacing workshop in London, UK. The authors applied a rigorous approach to categorize the challenges identified to be at the intersection of biofuels/bioenergy LCA and policy. Results and discussion The credibility of LCA is core to its use in policy. Even LCAs that comply with ISO standards and policy and regulatory instruments leave a great deal of scope for interpretation and flexibility. Within the bioenergy sector, this has led to frustration and at times a lack of obvious direction. This paper identifies the main challenge clusters: overarching issues, application and practice and value and ethical judgments. Many of these are reflective of the transition from application of LCA to assess individual products or systems to the wider approach that is becoming more common. Uncertainty in impact assessment strongly influences planning and compliance due to challenges in assigning accountability, and communicating the inherent complexity and uncertainty within bioenergy is becoming of greater importance. Conclusions The emergence of LCA in bioenergy governance is particularly significant because other sectors are likely to transition to similar governance models. LCA is being stretched to accommodate complex and broad policy-relevant questions, seeking to incorporate externalities that have major implications for long-term sustainability. As policy increasingly relies on LCA, the strains placed on the methodology are becoming both clearer and impedimentary. The implications for energy policy, and in particular bioenergy, are large

Possibilities of improving the bioethanol production from cornmeal by yeast saccharomyces cerevisiae var. ellipsoideus

Bioethanol has become one of the most promising biofuels today. In Serbia, the most suitable and available raw materials are conventional starch-based energy crops such as corn and triticale. Bioethanol production by simultaneous saccharification and fermentation (SSF) process of cornmeal using free and immobilized cells of Saccharomyces cerevisiae var. ellipsoideus yeast, with and without media supplementation (mineral salts ZnSO4·7H2O and MgSO4·7H2O), in a batch system is studied. The ethanol concentration after 48 h of SSF is increased for 6.68 % by yeast immobilization compared to the free cell system, and a percentage of the theoretical ethanol yield of 86.66 % is achieved. Further improvement is accomplished with the addition of mineral salts which contributed to the highest increase in ethanol concentration by 15.86 % compared to the SSF process with free yeast and without yeast activators. In this case, ethanol concentration of 10.23 % (w/w), percentage of the theoretical ethanol yield of 94.11 %, and glucose consumption of 98.32 % are achieved after 48 h of the SSF process.on, and the impact of the developed hydrogen production models on global warming is set forth