Cytotoxics compounded sterile preparation control by HPLC during a 16-month assessment in a French university hospital: importance of the mixing bags step

The Centralized Chemotherapy Reconstitution Unit (CCRU) of Paul Brousse Hospital Pharmacy Department assessed the reliability of its Cytotoxics Compounded Sterile Products (CCSP) preparation method in order to improve its CCSP quality assurance system. Five cytotoxic drugs — gemcitabine, 5-fluorouracil, docetaxel, paclitaxel, and oxaliplatin — were assayed by high performance liquid chromatography (HPLC) to determine CCSP concentration. During the observation period, 23,892 CCSP were prepared. Overall, 12,964 preparations contained one of the five analyzed drugs; 7382 (56.9%) out of 12,964 CCSP were analyzed by HPLC; 646 (8.8%) out of 7382 concentrations were outside ± 20% of the prescribed dose; 544 (84.2%) out of 646 were post-administration results and could not be verified. Out of 102 (15.8%) pre-administration results that were re-tested after re-shaking, 94 (92.2%) were found to be acceptable upon re-testing, and 8 (7.8%) were confirmed to be unacceptable and needed to be re-compounded. The 8.8% of tested CCSP were outside ± 20% of the prescribed dose, but extrapolating the results on re-tested CCSP, we can say that our CCSP preparation is reliable with an estimation of only 0.7% of 7382 CCSP analyzed, confirmed as being ± 20% outside the prescribed dose. Nevertheless, this ± 20% magnitude of error should be reduced. Based on pre-administration results, the primary cause of concentration errors appeared to be insufficient mixing of the finished product. Most CCSP dosages occurred after it had been administered, the organization should, therefore, be improved to include testing all CCSP prior to administration. Pharmaceutical companies should endeavor to manufacture compounded injectible drugs in a ‘ready to use’ form and provide vehicles in accurate volumes in order to improve compounding precision

Lowering the global warming impact of bridge rehabilitations by using Ultra High Performance Fibre Reinforced Concretes

Ultra-High Performance Fibre Reinforced Concrete (UHPFRC)is charact erized by aunique combination of extremely low permeability, high strength and deformability. Extensive R&D works and applications over the last 10 years have demonstrated that cast on site UHPFRC is afast, efficientand price competitive method for the repair/re habilitation of existing structures. More recently, an original concept of ECO- UHPFRC with ahigh dosage of mineral addition, alow clinker content, and amajority of local components has been applied successfully for the reh abilitation of abridge in Slovenia. The objective of the present study is to evaluate the global warming impact of bridge rehabilitations with different types of UHPFRC and to compare them to more standard solutions, both on the basis of the bridge rehabilitation performed in Slovenia. Life Cycle Assessment (LCA)methodology is used. The analysis shows that rehabilitations with UHPFRC, and even more ECO-UHPFRC, have alower impact than traditional methods over the life cycle

The political economy of the Jospin government

This article explores the political economy of the French Socialist Party (PS), beginning with the neo-liberal U-turn of 1983. It then charts the re-evaluation of the PS's political economic foundations after the 1993 defeat, the rejection of the neo-liberal 'pensée unique', and the rehabilitation of a broadly Keynesian frame of reference. The article goes on to explore how this shift has fed through into the Jospin government's policy and positions at both the national and international level. It explores aspirations to reinvent the EU as a Keynesian social democratic 'policy space', and at the national level, employment, macroeconomic, and structural policies

Embodied GHG emissions of buildings - Critical reflection of benchmark comparison and in-depth analysis of drivers

In the face of the unfolding climate crisis, the role and importance of reducing Greenhouse gas (GHG) emissions from the building sector is increasing. This study investigates the global trends of GHG emissions occurring across the life cycle of buildings by systematically compiling life cycle assessment (LCA) studies and analysing more than 650 building cases. Based on the data extracted from these LCA studies, the influence of features related to LCA methodology and building design is analysed. Results show that embodied GHG emissions, which mainly arise from manufacturing and processing of building materials, are dominating life cycle emissions of new, advanced buildings. Analysis of GHG emissions at the time of occurrence, shows the upfront \u27carbon spike\u27 and emphasises the need to address and reduce the GHG \u27investment\u27 for new buildings. Comparing the results with existing life cycle-related benchmarks, we find only a small number of cases meeting the benchmark. Critically reflecting on the benchmark comparison, an in-depth analysis reveals different reasons for cases achieving the benchmark. While one would expect that different building design strategies and material choices lead to high or low embodied GHG emissions, the results mainly correlate with decisions related to LCA methodology, i.e. the scope of the assessments. The results emphasize the strong need for transparency in the reporting of LCA studies as well as need for consistency when applying environmental benchmarks. Furthermore, the paper opens up the discussion on the potential of utilizing big data and machine learning for analysis and prediction of environmental performance of buildings

Plasma β-secretase1 concentrations correlate with basal forebrain atrophy and neurodegeneration in cognitively healthy individuals at risk for AD

BACKGROUND: Increased β-secretase 1 (BACE1) protein concentration, in body fluids, is a candidate biomarker of Alzheimer's disease (AD).We reported that plasma BACE1 protein concentrations are associated with the levels of brain amyloidβ (Αβ) accumulation in cognitively healthy individuals with subjective memory complaint (SMC). METHODS: In 302 individuals from the same cohort, we investigated the cross-sectional and longitudinal association between plasma BACE1 protein concentrations and AD biomarkers of neurodegeneration (plasma t-tau and Neurofilament light chain (NfL), fluorodeoxyglucose-positron emission tomography (FDG-PET), brain volumes in the basal forebrain [BF], hippocampus, and entorhinal cortex). RESULTS: We report a positive longitudinal correlation of BACE1 with both NfL and t-tau, as well as a correlation between annual BACE1 changes and bi-annual reduction of BF volume. We show a positive association between BACE1 and FDG-PET signal at baseline. CONCLUSIONS: The association between plasma BACE1 protein concentrations and BF atrophy we found in cognitively healthy individuals with SMC corroborates translational studies, suggesting a role of BACE1 in neurodegeneration

Mouse testis development and function are differently regulated by follicle-stimulating hormone receptors signaling during fetal and prepubertal life

It is currently admitted that Follicle-Stimulating Hormone (FSH) is physiologically involved in the development and function of fetal/neonatal Sertoli cells in the rat but not the mouse. However, FSH is produced by both species from late fetal life onwards. We thus reinvestigated the role of FSH in mouse testis development at day 0 (birth) 6, 8 and 10 post-partum (dpp) by using mice that lack functional FSH receptors (FSH-R(-/-)). At birth, the number and proliferative index of Sertoli cells were significantly lower in FSH-R(-/-) mice than in wild type neonates. Claudin 11 mRNA expression also was significantly reduced in FSH-R(-/-) testes at 0 and 8 dpp, whereas the mRNA levels of other Sertoli cell markers (Transferrin and Desert hedgehog) were comparable in FSH-R(-/-) and wild type testes. Conversely, AMH mRNA and protein levels were higher at birth, comparable at 6 dpp and then significantly lower in FSH-R(-/-) testes at 8-10 dpp in FSH-R(-/-) mice than in controls. Although the plasma concentration of LH and the number of Leydig cells were similar in FSH-R(-/-) and control (wild type), testosterone concentration and P450c17 mRNA expression were significantly increased in FSH-R(-/-) testes at birth. Conversely, at 10 dpp when adult Leydig cells appear, expression of the steroidogenic genes P450scc, P450c17 and StAR was lower in FSH-R(-/-) testes than in controls. In conclusion, our results show that 1) like in the rat, signaling via FSH-R controls Sertoli cell development and function during late fetal life in the mouse as well; 2) paracrine factors produced by Sertoli cells are involved in the FSH-R-dependent regulation of the functions of fetal Leydig cells in late fetal life; and 3) the role of FSH-R signaling changes during the prepubertal period

Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study

BACKGROUND: Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer's disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. METHODS: Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). RESULTS: We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. CONCLUSION: We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood

Wood in buildings: the right answer to the wrong question

Reducing the embodied emissions of materials for new construction and renovation of buildings is a key challenge for climate change mitigation around the world. However, as simply reducing emissions is not sufficient to meet the climate targets, using bio-based materials seems the only feasible choice as it permits carbon storage in buildings. Various studies have shown that bio-based materials allow turning overall life cycle impacts negative, therefore, having a cooling effect on the climate. In recent years, scholars and policy makers have focused almost exclusively on the advancement of wooden buildings. Timber structures stand out as they can be prefabricated and used for high-rise buildings. Yet, one important aspect seems to be overlooked: the consideration of supply and demand. Large forest areas that allow sustainable sourcing of woody biomass only exist in the Northern hemisphere, notably in North America and Europe. In these regions, though, urbanization rates are mostly stagnating, meaning new construction rates are low. The largest amount of material requirements in these regions are derived from the refurbishment of the existing stock. Moreover, in areas where structural material is needed for new construction, in Asia, Africa and South America, rain forests need to be protected. Therefore, we need to rethink the desire to find one solution and carelessly implement it everywhere. Instead, we need to consider locally available material and know-how for grounded material choices. This paper explores the supply of a range of bio-based materials and matches it against the material demand of global building stocks. It is based on various previous studies by the authors, of South Africa, China, Portugal, and more. The analysis divides between structural materials for new construction, such as wood and bamboo, and thermal insulation materials for the refurbishment of existing buildings, such as straw and hemp. The results emphasize the need for diversifying bio-based material solutions

Improving rammed earth walls' sustainability through life cycle assessment (LCA)

The main objective of the BTP1000 project was to design (and build) an office building (€coffice) that would comply to the PassivHauss principles, offer a very high comfort and integrate different sustainability features, but cost no more than a traditional building. In order to achieve those objectives, an integrated iterative design approach was followed. From the beginning of the project, all stakeholders and various building specialists contributed to the decision making process, and design alternatives where evaluated from various perspectives (e.g. energy performance, comfort, life cycle cost and impact,…). The present paper focuses on how life cycle analysis (LCA) and life cycle costing (LCC) were used to integrate environmental and economic dimensions in the design process of the building envelope and how the results influenced final design options. LCA and LCC studies first compared different types of façades. The best compromise between LCC and LCA results, practical implementation, and thermal comfort were then selected for implementation. Subsequently, parametric energetic simulation results (combining heating, cooling, lighting, and ventilation) were used as input for LCA and LCC studies in order to optimise the insulation level of the building fabric elements (outer walls, roof, ground floor, glazing). In conclusion, LCC and LCA were very useful in the integrated design process and results showed the importance of taking into account not only the energy use for heating and cooling, but also for lighting into the building fabric optimisation.The main objective of the BTP1000 project was to design (and build) an office building (€coffice) that would comply to the PassivHauss principles, offer a very high comfort and integrate different sustainability features, but cost no more than a traditional building. In order to achieve those objectives, an integrated iterative design approach was followed. From the beginning of the project, all stakeholders and various building specialists contributed to the decision making process, and design alternatives where evaluated from various perspectives (e.g. energy performance, comfort, life cycle cost and impact,…). The present paper focuses on how life cycle analysis (LCA) and life cycle costing (LCC) were used to integrate environmental and economic dimensions in the design process of the building envelope and how the results influenced final design options. LCA and LCC studies first compared different types of façades. The best compromise between LCC and LCA results, practical implementation, and thermal comfort were then selected for implementation. Subsequently, parametric energetic simulation results (combining heating, cooling, lighting, and ventilation) were used as input for LCA and LCC studies in order to optimise the insulation level of the building fabric elements (outer walls, roof, ground floor, glazing). In conclusion, LCC and LCA were very useful in the integrated design process and results showed the importance of taking into account not only the energy use for heating and cooling, but also for lighting into the building fabric optimisation