Iron overload, resulting from blood transfusions in patients with chronic anemias, has historically been controlled with regular deferoxamine, but its parenteral requirement encouraged studies of ...orally-active agents, including deferasirox and deferiprone. Deferasirox, licensed by the US Food and Drug Administration in 2005 based upon the results of randomized controlled trials, is now first-line therapy worldwide. In contrast, early investigator-initiated trials of deferiprone were prematurely terminated after investigators raised safety concerns. The FDA declined market approval of deferiprone; years later, it licensed the drug as "last resort" therapy, to be prescribed only if first-line drugs had failed. We undertook to evaluate the long-term effectiveness and toxicities of deferiprone and deferasirox in one transfusion clinic.
Under an IRB-approved study, we retrospectively inspected the electronic medical records of consented iron-loaded patients managed between 2009 and 2015 at The University Health Network (UHN), Toronto. We compared changes in liver and heart iron, adverse effects and other outcomes, in patients treated with deferiprone or deferasirox.
Although deferiprone was unlicensed in Canada, one-third (n = 41) of locally-transfused patients had been switched from first-line, licensed therapies (deferoxamine or deferasirox) to regimens of unlicensed deferiprone. The primary endpoint of monitoring in iron overload, hepatic iron concentration (HIC), increased (worsened) during deferiprone monotherapy (mean 10±2-18±2 mg/g; p < 0.0003), exceeding the threshold for life-threatening complications (15 mg iron/g liver) in 50% patients. During deferasirox monotherapy, mean HIC decreased (improved) (11±1-6±1 mg/g; p < 0.0001). Follow-up HICs were significantly different following deferiprone and deferasirox monotherapies (p < 0.0000002). Addition of low-dose deferoxamine (<40 mg/kg/day) to deferiprone did not result in reductions of HIC to <15 mg/g (baseline 20±4 mg/g; follow-up, 18±4 mg/g; p < 0.2) or in reduction in the proportion of patients with HIC exceeding 15 mg/g (p < 0.2). During deferiprone exposure, new diabetes mellitus, a recognized consequence of inadequate iron control, was diagnosed in 17% patients, most of whom had sustained HICs exceeding 15 mg/g for years; one woman died after 13 months of a regimen of deferiprone and low-dose deferasirox. During deferiprone exposure, serum ALT increased over baseline in 65% patients. Mean serum ALT increased 6.6-fold (p < 0.001) often persisting for years. During deferasirox exposure, mean ALT was unchanged (p < 0.84). No significant differences between treatment groups were observed in the proportions of patients estimated to have elevated cardiac iron.
Deferiprone showed ineffectiveness and significant toxicity in most patients. Combination with low doses of first-line therapies did not improve the effectiveness of deferiprone. Exposure to deferiprone, over six years while the drug was unlicensed, in the face of ineffectiveness and serious toxicities, demands review of the standards of local medical practice. The limited scope of regulatory approval of deferiprone, worldwide, should restrict its exposure to the few patients genuinely unable to tolerate the two effective, first-line therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The β-Thalassemias Olivieri, Nancy F
The New England journal of medicine,
07/1999, Letnik:
341, Številka:
2
Journal Article
Recenzirano
In 1925, Thomas Cooley and Pearl Lee described a form of severe anemia, occurring in children of Italian origin and associated with splenomegaly and characteristic bone changes.
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Over the next ...decade, a milder form was described independently by several Italian investigators.
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Because all early cases were reported in children of Mediterranean origin, the disease was later termed thalassemia, from the Greek word for sea,
thalassa
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Over the next 20 years, it became apparent that Cooley and Lee had described the homozygous or compound heterozygous state for a recessive mendelian disorder not confined to the Mediterranean, but occurring widely . . .
The use of vegetal systems in façades affects the reduction of the buildings' energy demand, the attenuation of the urban heat island (UHI) and the filtration of pollutants present in the air. Even ...so, up to now the knowledge about the effect of this type of systems on the thermal performance of insulated façades is limited. This article presents the results of an experimental study carried out in a vegetal façade located in a continental Mediterranean climate zone. The objective is to study the effect of a vegetal finishing, formed by plants and substrate, on the thermal-energy performance of an insulated façade under summer conditions.
To this effect, the thermal data obtained from two full-scale experimental mock-ups of the same dimensions and composition of the enclosure and only different in the south façade's enclosure where one incorporates a vegetation layer are compared and analysed.
The results show that, in spite of the high thermal resistance of the enclosure, the effect of the vegetation is very positive, particularly in the warmer hours of the day. Therefore, vegetal façades can be used as a passive cooling strategy, reducing the consumption of energy for refrigeration and improving the comfort conditions of the users.
•A full-scale insulated vegetal façade was monitored in a Mediterranean climate.•The effect of the vegetation is very positive particularly in the warmest hours.•The maximum temperature time lag enables the utilization of the natural ventilation.•Vegetal façades entail a reduction of operating temperature favouring users' comfort.•Vegetal façades are passive cooling strategies that reduce the consumption of energy.
•Design development and construction of an outdoor testing facility for STPV modules.•Global performance assessment of STPV modules in real operation conditions.•STPV solar gains and heat losses ...exceed the values achieved by a reference glass.•STPV daylight factor ranges between 1% (10S) and 8% (40S).•Transparency degree is not the most determining factor for the STPV electrical performance.
In this paper, a methodology for the integral energy performance characterization (thermal, daylighting and electrical behavior) of semi-transparent photovoltaic modules (STPV) under real operation conditions is presented. An outdoor testing facility to analyze simultaneously thermal, luminous and electrical performance of the devices has been designed, constructed and validated. The system, composed of three independent measurement subsystems, has been operated in Madrid with four prototypes of a-Si STPV modules, each one corresponding to a specific degree of transparency. The extensive experimental campaign, continued for a whole year rotating the modules under test, has validated the reliability of the testing facility under varying environmental conditions.
The thermal analyses show that both the solar protection and insulating properties of the laminated prototypes are lower than those achieved by a reference glazing whose characteristics are in accordance with the Spanish Technical Building Code. Daylighting analysis shows that STPV elements have an important lighting energy saving potential that could be exploited through their integration with strategies focused to reduce illuminance values in sunny conditions. Finally, the electrical tests show that the degree of transparency is not the most determining factor that affects the conversion efficiency.
Within the building energy saving strategies, BIPV (building integrated photovoltaic systems) present a promising potential based on the close relationship existing between these multifunctional ...systems and the overall building energy balance. Building integration of STPV (semi-transparent photovoltaic) elements affects deeply the building energy demand since it influences the heating, cooling and lighting loads as well as the local electricity generation. This work analyses over different window-to-wall ratios the overall energy performance of five STPV elements, each element having a specific degree of transparency, in order to assess the energy saving potential compared to a conventional solar control glass compliant with the local technical standard. The prior optical characterization, focused to measure the spectral properties of the elements, was experimentally undertaken. The obtained data were used to perform simulations based on a reference office building using a package of specific software tools (DesignBuilder, EnergyPlus, PVsyst, and COMFEN) to take proper account of the STPV peculiarities. To evaluate the global energy performance of the STPV elements a new Energy Balance Index was formulated. The results show that for intermediate and large façade openings the energy saving potential provided by the STPV solutions ranges between 18% and 59% compared to the reference glass.
•Experimental characterisation of semitransparent photovoltaic elements spectral properties.•New index formulation to assess the global energy performance of STPV (semi-transparent photovoltaic) elements.•Overall energy performance simulation carried out using a package of specific tools.•Compared to standard solutions, STPV energy saving potential ranges between 5 and 59%.•Energy saving potential depends on window-to-wall ratio and STPV transparency degree.
The Life-Cycle Assessment (LCA) is a standard approach for evaluating the environmental impacts of products and processes. This paper presents the LCA of Living Wall Systems (LWS), a new technology ...for greening the building envelope and improve sustainability. Impacts of manufacture, operation, and use of the systems selected, were evaluated through an LCA. LWS are closely related to several environmental benefits, including improved air quality, increased biodiversity, mitigation of heat island effects, and reduced energy consumption due to savings in indoor cooling and heating. Two prototypes have been selected, taking into account the modularity and the use of organic substrate as selection criteria. The systems evaluated were a plastic-based modular system and a felt-based modular system. The inventory data was gathered through the manufacturers. The LCA approach has been used to assess the impact of these solutions by focusing on the construction phase and its contribution to both the energy balance and the entire life cycle of a building. This approach has never been done before for LWS. The study found that out of the two systems through the manufacturing, construction, and maintenance stage of the LCA, the felt-based LWS has an impact on almost 100% of the impact categories analyzed, while plastic-based LWS has the lowest influence on the total environmental impact.
•Two prototypes of modular living wall systems analyzed through Life Cycle Assessment (LCA) method.•Life cycle approach to evaluating environmental impact and energy savings on buildings of the living wall systems as a passive system.•The environmental performance of living wall systems can be improved by selecting materials according to LCA results.
Green walls can act as natural thermal regulators, reducing solar radiation on surfaces and providing cooling due to shading and evapotranspiration. Several studies have investigated the cooling ...effects of a bare wall, in contrast to a vegetated wall, as well as the correlation between temperature reduction and system characteristics. In the present work, we analyze the influence of the orientation of a green wall on its ability to reduce surface temperatures in a Mediterranean climate. Environmental variables such as irradiation and air temperature have been considered. A real-time monitoring system has been used, with a database of three years of measurements. Results show that on average, the control temperature is greater than the green wall temperature with maximum differences of 20 °C in summer and 8 °C in winter in the south wall surface. During the summer, the temperature reduction in the south façade occurs mainly in the central hours of the day, while in the west façade it occurs mainly in the afternoon. Being the summer the most relevant season for the use of green walls, this information is very valuable as it allows the designers to know at what time of day the façade provides a temperature reduction, depending on the orientation.
•Effect of green walls on the surface temperature under different orientations.•Experimental study done on a real building located at Madrid under real conditions.•More than three years of monitored data by means of a real-time monitoring system.•The temperature behind the green wall is up to 20°C lower than on the control one.•The effect of the green wall is different depending on the orientation.
Type 2 diabetes mellitus (T2DM) is a major cause of cardiovascular (CV) disease. Several large clinical trials have shown that the risk for patients with diabetes of developing CV complications is ...only partially reduced by early, intensive glycaemic control and lifestyle interventions, and that such complications result from changes in complex, not fully explored networks that contribute to the maintenance of endothelial function. The accumulation of senescent cells and the low‐grade, systemic, inflammatory status that accompanies aging (inflammaging) are involved in the development of endothelial dysfunction. Such phenomena are modulated by epigenetic mechanisms, including microRNAs (miRNAs). MiRNAs can modulate virtually all gene transcripts. They can be secreted by living cells and taken up in active form by recipient cells, providing a new communication tool between tissues and organs. MiRNA deregulation has been associated with the development and progression of a number of age‐related diseases, including the enduring gene expression changes seen in patients with diabetes. We review recent evidence on miRNA changes in T2DM, focusing on the ability of diabetes‐associated miRNAs to modulate endothelial function, inflammaging and cellular senescence. We also discuss the hypothesis that miRNA‐containing extracellular vesicles (i.e. exosomes and microvesicles) could be harnessed to restore a ‘physiological’ signature capable of preventing or delaying the harmful systemic effects of T2DM.
•We monitored a high insulted real-scale green roof in a Mediterranean climate.•It was monitored during three summers characterized by diverse vegetation density.•Results show that high vegetation ...density green roof is a passive cooling system.•It reduces thermal load of about 60% compared with the roof with no vegetation.•A roofing resistance numerical model was developed and experimentally validated.
This paper presents the results of an experimental study carried out on an extensive green roof situated in a Mediterranean coastal climate zone. The aim of the study is to analyze the thermal energy behavior of a green roof during the summer so as to evaluate the effect of vegetation density on the energy performance of the roof and to identify the characteristics of the plants and substrate that have the greatest impact. The paper describes the results of monitoring carried out during the summer in 2010, 2011 and 2012, the development of a numerical model for calculating the thermal resistance of the substrate and the vegetation and the procedure for validating the model using the experimental data. The results show that a green roof which has high vegetation density acts as a passive cooling system when the roof is highly insulated (U value=0.24W/(m2K)) and that in these conditions the incoming thermal gain is about 60% lower than when the roof has no vegetation.
•A real-scale vegetal façade was monitored during three years in a Mediterranean climate.•Results show that the vegetation layer improves interior environmental conditions.•A predictive numerical ...model was fitted and experimentally validated.•Results show the high accuracy of the model, being the R-squared around 85%.•The model is suitable for buildings located in similar climates to the one studied.
This article presents the results of an experimental study carried out in a vegetal façade situated in a locality close to Madrid.
The objectives of the study are to develop a performance predictive model of a vegetal façade whose independent variables are irradiance, exterior temperature and relative humidity, based on the effect of the vegetation on the environmental conditions of the building, as well as to characterize thermally the vegetal element by comparing two identical enclosures (with a vegetal layer present in one of them being the only difference).
The results of the three-year monitoring period are analyzed by means of statistical data processing and an autoregressive model is fitted. This model estimates the temperature difference between both enclosures. The validation of the model based on the experimental data is done subsequently.
Once the improvements caused by the vegetation on the interior environmental conditions of the building have been quantified, the results show that it is possible to predict with high accuracy the vegetation's performance, being the multiple R-squared of the estimated models around 85%.
Furthermore, the application of the model is suitable for other buildings located in a similar climate to the one studied, as the independent variables exclusively depend on climate conditions.
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