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- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Aprile, E., et al.
(author)
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The XENON1T dark matter experiment
- 2017
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:12
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Journal article (peer-reviewed)abstract
- The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2t liquid xenon inventory, 2.0t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.
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| 3. |
- Abila, R., et al.
(author)
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Oil extraction imperils Africa’s Great Lakes
- 2016
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6312, s. 561-562
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Journal article (other academic/artistic)abstract
- As the world's demands for hydrocarbons increase (1), remote areas previously made inaccessible by technological limitations are now being prospected for oil and gas deposits. Virtually unnoticed by the public, such activities are ongoing in the East African Great Lakes region, threatening these ecosystems famed for their hyper-diverse biota, including the unique adaptive radiations of cichlid fishes (2). Countries in the region see exploitation of hydrocarbon reserves as a vital economic opportunity. In the Lake Albert region of Uganda, for example, the government foresees a $3.6 billion oil profit per year starting in 2018—a sum almost as high as the country's current annual budget (3). However, oil extraction in the East African Great Lakes region poses grave risks to the environment and local communities.
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| 7. |
- Abreu, Soraia Carvalho, et al.
(author)
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Lung Inflammatory Environments Differentially Alter Mesenchymal Stromal Cell Behavior
- 2019
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In: American Journal of Physiology: Lung Cellular and Molecular Physiology. - : American Physiological Society. - 1522-1504 .- 1040-0605. ; 317:6, s. 823-831
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Journal article (peer-reviewed)abstract
- Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally-induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed to in vitro culture conditions from bronchoalveolar lavage fluid (BALF) samples obtained from patients with either the acute respiratory distress syndrome (ARDS) or with other lung diseases including acute respiratory exacerbations of cystic fibrosis (CF) (non-ARDS). hMSCs were subsequently assessed for time- and BALF concentration-dependent effects on mRNA expression of selected pro- and anti-inflammatory mediators, and for overall patterns of gene and mRNA expression. Both common and disease specific-patterns were observed in gene expression of different hMSC mediators, notably interleukin (IL)-6. Conditioned media obtained from non-ARDS BALF-exposed hMSCs was more effective in promoting an anti-inflammatory phenotype in monocytes than was conditioned media from ARDS BALF-exposed hMSCs. Neutralizing IL-6 in the conditioned media promoted generation of anti-inflammatory monocyte phenotype. These results demonstrated that different lung inflammatory environments differentially alter hMSC behavior. Further identification of these interactions and the driving mechanisms may influence clinical use of MSCs for treating lung diseases.
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| 8. |
- Alves, L., et al.
(author)
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Unusual extraction and characterization of nanocrystalline cellulose from cellulose derivatives
- 2015
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In: Journal of Molecular Liquids. - : Elsevier BV. - 0167-7322 .- 1873-3166. ; 210, s. 106-112
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Journal article (peer-reviewed)abstract
- Unlike many nanomaterials, nanocrystalline cellulose (CNC) is not synthesized from molecular or atomic components but rather extracted from naturally occurring cellulose. Undoubtedly, the exploitation of CNCs will become a bridge between nanoscience and natural resource products, which could play a major role in reviving the forest industry. In this work, CNC was successfully extracted from unusual sources, hydroxypropyl methylcellulose (HPMC) and carboxymethylcellulose (CMC). The extracted crystallites were purified and further characterized by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and dynamic light scattering (DLS). The average size of the CNCs extracted from HPMC and CMC was found to be less (and with lower zeta potential) than the ones extracted from microcrystalline cellulose (MCC). On the other hand, FTIR and XRD revealed that native HPMC and CMC are unexpectedly highly crystalline and hence can be used as a source for CNCs. © 2014 Elsevier B.V.All rights reserved.
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| 15. |
- Balaghi I., M. H., et al.
(author)
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An Optimal LQG Controller for Stochastic Event-triggered Scheduling over a Lossy Communication Network
- 2018
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In: IFAC-PapersOnLine. - : Elsevier. - 2405-8963. ; 51:23, s. 58-63
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Journal article (peer-reviewed)abstract
- We consider a networked control loop in which the sensors acquire partial state information and communicate to a remote controller through a lossy communication network. A scheduler, collocated with the sensors, decides to transmit a locally estimated state to the controller based on an event-triggered transmission policy with stochastic thresholds. Assuming that the local estimator either senses the communication channel or receives an ideal acknowledgment from the remote estimator, then the optimal control law can be shown to be a linear function of the conditional expectation of the state. However, the probability distribution of the state conditioned on the information available to the controller based on the mentioned transmission policy and network is not Gaussian, but rather described by a sum of Gaussians with an increasing number of terms at every time-step. We show that the optimal LQG control law can be determined without tracking this probability distribution for finding its expected value. Moreover, we establish that the stochastic event-triggered scheduler can be appropriately regulated in order to achieve a desired triggering probability at every time-step.
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| 16. |
- Balaghi, M. Hadi I., et al.
(author)
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A Decentralized Consistent Policy for Event-triggered Control over a Shared Contention-based Network
- 2018
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In: 2018 IEEE Conference on Decision and Control (CDC). - : IEEE. - 9781538613955 ; , s. 1719-1724
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Conference paper (peer-reviewed)abstract
- We consider a network of several independent linear systems controlled over a shared communication network. Data transmissions pertaining to each control loop are arbitrated by a scheduler collocated with the plant's sensors that transmits the state information to the corresponding remote controller collocated with the plant's actuators. The shared communication channel is assumed to be operating based on a contention-based protocol, endowing the networked control system with desirable reconfigurable and scalable features. We propose a class of scheduling policies which admit a decentralized optimal control implementation and an event-triggered policy within this class which is shown to be consistent, i.e. it results in a better control performance for any linear system, measured by an average quadratic cost than its non-event-based counterpart.
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| 22. |
- Tordo, Julie, et al.
(author)
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A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency
- 2018
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141:7, s. 2014-2031
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Journal article (peer-reviewed)abstract
- Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.
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