Objectif Comparer l'efficacité et la tolérance du liraglutide par rapport au lixisenatide en association à la metformine (MET) chez des patients diabétiques de type 2 (DT2) insuffisamment contrôlés ...sous MET seule. Matériels et Méthodes Essai randomisé contrôlé, en ouvert de 26 semaines. Des patients DT2 (âge ≥ 18 ans, 7,5 % ≥ HbA1c ≤ 10,5 %, IMC ≥ 20 kg/m2 ) ont été randomisés selon un ratio 1 : 1 pour recevoir soit le liraglutide 1,8 mg/j, soit le lixisenatide 20 μg/j en association à la la MET. Le liraglutide était administré à n'importe quel moment de la journée, le lixisenatide était administré une heure avant le repas du matin ou du soir. Résultats 404 patients DT2 (60 % d'hommes, âge moyen 56 ans, IMC 35 kg/m2 , HbA1c 8,4 %, durée du diabète 6,4 ans) ont été randomisés. Après 26 semaines de traitement, la réduction de l'HbA1c sous liraglutide a été supérieure par rapport au lixisenatide (1,83 vs 1,21 %, p < 0,001), avec davantage de patients atteignant l'objectif d'HbA1c < 7 % (74,2 vs 45,5 %, p < 0,001). La baisse de la glycémie à jeun a été plus importante sous liraglutide (2,85 vs 1,70 mmol/l, P < 0,001). Le profil glycémique global en 9 points était significativement amélioré sous liraglutide, cependant l'excursion glycémique post prandiale était significativement plus basse pour le repas suivant l'administration du lixisenatide. La perte pondérale a été similaire dans les 2 groupes (− 4,3 kg pour lira, − 3,7 kg pour lixi, p = ns). Les profils de tolérance ont été globalement comparables. Les événements indésirables les plus fréquents étaient digestifs (nausées : 21,8 % pour lira et lixi ; diarrhées : 12,4 % pour lira, 9,9 % pour lixi). Les épisodes d'hypoglycémies confirmées ont été rares (hypoglycémie sévère ou glycémie < 3,1 mmol/l), sans aucun épisode sévère. Conclusions Le liraglutide en association à la metformine a été plus efficace que le lixisenatide en termes de contrôle glycémique. Une perte pondérale significative a été observée avec les deux traitements. Les profils de tolérance ont été similaires avec essentiellement des troubles digestifs et un risque hypoglycémique faible.
ABSTRACT
We analyse the late time evolution of 12 supernovae (SNe) occurring over the last ∼41 yr, including nine Type IIP/L, two IIb, and one Ib/c, using UBVR optical data from the Large Binocular ...Telescope (LBT) and difference imaging. We see late time (5–42 yr) emission from nine of the eleven Type II SNe (eight Type IIP/L, one IIb). We consider radioactive decay, circumstellar medium (CSM) interactions, pulsar/engine driven emission, dust echoes, and shock perturbed binary companions as possible sources of emission. The observed emission is most naturally explained as CSM interactions with the normal stellar winds of red supergiants with mass-loss rates in the range −7.9 ≲ log10(M⊙ yr−1) ≲ −4.8. We also place constraints on the presence of any shock heated binary companion to the Type Ib/c SN 2012fh and provide progenitor photometry for the Type IIb SN 2011dh, the only one of the six SNe with pre-explosion LBT observations where the SN has faded sufficiently to allow the measurement. The results are consistent with measurements from pre-explosion Hubble Space Telescope images.
This article analyses the political economy of the Bus Rapid Transit project implemented in Dar es Salaam between 2002 and 2014. It discusses the recent rapid growth of Bus Rapid Transit systems and ...the vested interests of the actors promoting them as a "win-win" solution to tackle the crisis of public transport in developing countries. The article discredits such "win-win" narratives by showing what some Tanzanian actors stood to lose from the implementation of the Dar es Salaam Rapid Transit scheme and their capacity to resist the project. It analyses tensions over the inclusion of the current public transport workforce, employment destruction, displacement of current paratransit operators, compensation, and the affordability of the new service. The article argues that slow implementation of the transport system was rooted in the tepid commitment to the project by the Tanzanian government. In turn, this lack of political will can be explained by domestic politics, and in particular the government's attempt to respond to the priorities of the World Bank without alienating local actors, some of whom wield considerable electoral power.
Magnetic nanoparticles are increasingly used in medical applications, including cancer treatment by magnetic hyperthermia. This protocol describes a solvothermal-based process to prepare, at the gram ...scale, ferrite nanoparticles with well-defined shape, i.e., nanocubes, nanostars and other faceted nanoparticles, and with fine control of structural/magnetic properties to achieve point-of-reference magnetic hyperthermia performance. This straightforward method comprises simple steps: (i) making a homogeneous alcoholic solution of a surfactant and an alkyl amine; (ii) adding an organometallic metal precursor together with an aldehyde molecule, which acts as the key shape directing agent; and (iii) reacting the mixture in an autoclave for solvothermal crystallization. The shape of the ferrite nanoparticles can be controlled by the structure of the aldehyde ligand. Benzaldehyde and its aromatic derivatives favor the formation of cubic ferrite nanoparticles while aliphatic aldehydes result in spherical nanoparticles. The replacement of the primary amine, used in the nanocubes synthesis, with a secondary/tertiary amine results in nanoparticles with star-like shape. The well-defined control in terms of shape, narrow size distribution (below 5%), compositional tuning and crystallinity guarantees the preparation, at the gram scale, of nanocubes/star-like nanoparticles that possess, under magnetic field conditions of clinical use, specific adsorption rates comparable to or even superior to those obtained through thermal decomposition methods, which are typically prepared at the milligram scale. Here, gram-scale nanoparticle products with benchmark features for magnetic hyperthermia applications can be prepared in ~10 h with an average level of expertise in chemistry.
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden. This systematic literature review aimed to highlight the economic burden ...associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.
Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases. Supplemental searches from relevant 2015-2016 conferences were also performed. Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria. Studies were grouped by the type of economic outcome presented (HRU or costs). Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.
In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs. Most of the studies (94%) reported on data from either Europe or North America. Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations. Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits. Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations. Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.
Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use. Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures.
ABSTRACT
Gravitational waves provide a unique tool for observational astronomy. While the first LIGO–Virgo catalogue of gravitational-wave transients (GWTC-1) contains 11 signals from black hole and ...neutron star binaries, the number of observations is increasing rapidly as detector sensitivity improves. To extract information from the observed signals, it is imperative to have fast, flexible, and scalable inference techniques. In a previous paper, we introduced bilby: a modular and user-friendly Bayesian inference library adapted to address the needs of gravitational-wave inference. In this work, we demonstrate that bilby produces reliable results for simulated gravitational-wave signals from compact binary mergers, and verify that it accurately reproduces results reported for the 11 GWTC-1 signals. Additionally, we provide configuration and output files for all analyses to allow for easy reproduction, modification, and future use. This work establishes that bilby is primed and ready to analyse the rapidly growing population of compact binary coalescence gravitational-wave signals.
We present a flexible, compact antenna system intended for telemedicine applications. The design is based on an M-shaped printed monopole antenna operating in the Industrial, Scientific, and Medical ...(ISM) 2.45 GHz band integrated with a miniaturized slotted Jerusalem Cross (JC) Artificial Magnetic Conductor (AMC) ground plane. The AMC ground plane is utilized to isolate the user's body from undesired electromagnetic radiation in addition to minimizing the antenna's impedance mismatch caused by the proximity to human tissues. Specific Absorption Rate (SAR) is analyzed using a numerical human body model (HUGO) to assess the feasibility of the proposed design. The antenna expresses 18% impedance bandwidth; moreover, the inclusion of the AMC ground plane increases the front to back ratio by 8 dB, provides 3.7 dB increase in gain, in addition to 64% reduction in SAR. Experimental and numerical results show that the radiation characteristics, impedance matching, and SAR values of the proposed design are significantly improved compared to conventional monopole and dipole antennas. Furthermore, it offers a compact and flexible solution which makes it a good candidate for the wearable telemedicine application.
Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer
. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell ...death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies
. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood. Here we report that V-domain immunoglobulin suppressor of T cell activation (VISTA) engages and suppresses T cells selectively at acidic pH such as that found in tumour microenvironments. Multiple histidine residues along the rim of the VISTA extracellular domain mediate binding to the adhesion and co-inhibitory receptor P-selectin glycoprotein ligand-1 (PSGL-1). Antibodies engineered to selectively bind and block this interaction in acidic environments were sufficient to reverse VISTA-mediated immune suppression in vivo. These findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement.
Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with ...vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.
ABSTRACT
The progenitor of SN 2023ixf was an ∼104.8 to $10^{5.0}\, \text{L}_\odot$ star (∼9 to $14\, \text{M}_\odot$ at birth) obscured by a dusty $\dot{M} \simeq 10^{-5}\, \text{M}_\odot \rm \, ...yr^{-1}$ wind with a visual optical depth of τV ≃ 13. This is required by the progenitor spectral energy distribution, the post-SN X-ray and H α luminosities, and the X-ray column density estimates. In Large Binocular Telescope (LBT) data spanning 5600 to 400 d before the supernova (SN), there is no evidence for optical variability at the level of $\sim 10^3\, \text{L}_\odot$ in R band, roughly three times the predicted luminosity of the obscured progenitor. This constrains direct observation of any pre-SN optical outbursts where there are LBT observations. However, models of the effects of any pre-SN outburst on the dusty wind show that an outburst of essentially any duration exceeding ∼5 times the luminosity of the progenitor would have detectable effects on the dust optical depth for decades. While the dust obscuration here is high, all red supergiants have dusty winds, and the destruction (or formation) of dust by even short-lived transients will always have long-term effects on the observed brightness of the star because changes in the dust optical depths after a luminous transient occur very slowly.
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