Abstract
Background
Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While ...most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings.
Methods
endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations.
Discussion
The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide.
Trial registration
ClinicalTrials.gov
Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.
•Total conversión hematite-magnetite can be performed by soft and wet ball milling.•Ball milling in presence of PEG hepls to stabilize magnetite nanoparticles.•Ball milling in presence of PEG helps ...to reduce particle size distribution of MNPs.
We present the synthesis and characterization ofmagnetite-maghemite nanoparticles obtained by mechanical milling of sub micrometric hematite in presence of polyethylene glycol (PEG) as stabilizing medium. Nanoparticles were obtained in a milling time of 24 h, being their aggregation and particle size distribution less than those obtained by us in a previous work employing a mixture of hematite and deionized water as precursor material.X-ray and room temperature Mössbauer measurements confirmed that milling products are composed only by thephases magnetite-maghemite. TEM micrographs showed quasi-spherical particles with low aggregation andmean diameteraround 14 nm. Room temperature magnetization loops are consistent withferrimagnetic multi domain nanoparticles, with saturation magnetization around 62 A m2 kg−1 and coercive field around 10.2 kA m−1. The results suggest that mechanical milling in presence of polyethylene glycol is a simple and efficient route to produce magnetite-maghemite nanoparticles with good magnetization, which can be useful for applications in nanotechnology.
The aim of this study was to develop a system to classify the marbling of beef using the hyperspectral imaging technology. The Japanese standard classification of the degree of marbling of beef was ...used as reference and twelve standards were digitized to obtain the parameters of shape and spatial distribution of marbling of each class. A total of 35 samples M. longissmus dorsi muscle were scanned by the hyperspectral imaging system of 400–1000 nm in reflectance mode. The wavelength of 528nm was selected to segment the sample and the background, and 440nm was used for classified the samples. Processing algorithms on image, based on decision tree method, were used in the region of interest obtaining a classification error of 0.08% in the building stage. The results showed that the proposed technique has a great potential, as a non-destructive and fast technique, that can be used to classify beef with respect to the degree of marbling.
•The proposed algorithm improves the predictive level of marbling in meat.•The proposed method for meat classification is fast and non-destructive.•A spectral difference of 440nm in the “decision tree” classifies fat and meat pixels.•No statistical differences between the marbling based in images and the traditional method
We present the process of synthesis and characterization of magnetite-maghemite nanoparticles by the ball milling method. The particles were synthesized in a planetary ball mill equipped with vials ...and balls of tempered steel, employing dry and wet conditions. For dry milling, we employed microstructured analytical-grade hematite (α-Fe
2
O
3
), while for wet milling, we mixed hematite and deionized water. Milling products were characterized by X-ray diffraction, transmission electron microscopy, room temperature Mössbauer spectroscopy, vibrating sample magnetometry, and atomic absorption spectroscopy. The Mössbauer spectrum of the dry milling product was well fitted with two sextets of hematite, while the spectrum of the wet milling product was well fitted with three sextets of spinel phase. X-ray measurements confirmed the phases identified by Mössbauer spectroscopy in both milling conditions and a reduction in the crystallinity of the dry milling product. TEM measurements showed that the products of dry milling for 100 h and wet milling for 24 h consist of aggregates of nanoparticles distributed in size, with mean particle size of 10 and 15 nm, respectively. Magnetization measurements of the wet milling product showed little coercivity and a saturation magnetization around 69 emu g
−1
, characteristic of a nano-spinel system. Atomic absorption measurements showed that the chromium contamination in the wet milling product is approximately two orders of magnitude greater than that found in the dry milling product for 24 h, indicating that the material of the milling bodies, liberated more widely in wet conditions, plays an important role in the conversion hematite-spinel phase.
Chagas disease (CD) is considered by the World Health Organisation (WHO) a neglected disease endemic to the Americas, but it has spread throughout the world due to migrations. The disease is almost ...100% curable if detected in time. Still, the lack of rapid diagnostic tests with sufficient sensitivity and specificity leads to a chronic phase with a mortality of about 50,000 people worldwide per year.
Using the total proteins extracted from serum samples of patients confirmed with chronic phase CD; we performed the Bio-SELEX strategy. The best aptamers were selected using next-generation sequencing (NGS) based on their most abundant sequences (reads and rpm). Then, selected aptamers were used to isolate potential biomarkers directly from serum samples of patients with chronic phase CD using pull-down and mass spectrometry experiments.
CH1 aptamer was the aptamer selected after the NGS results analysis. The pull-down and mass spectrometry experiments identified the presence of the ATPase alpha subunit of
circulating in serum samples of patients with chronic phase CD.
We report the ATPase alpha subunit of
as a potential biomarker for chronic phase CD and CH1 aptamer as a potential tool for diagnosing CD.
We present measurements of ν(μ) charged-current cross section ratios on carbon, iron, and lead relative to a scintillator (CH) using the fine-grained MINERvA detector exposed to the NuMI neutrino ...beam at Fermilab. The measurements utilize events of energies 2<E(ν)<20 GeV, with ⟨E(ν)⟩ = 8 GeV, which have a reconstructed μ(-) scattering angle less than 17° to extract ratios of inclusive total cross sections as a function of neutrino energy E(ν) and flux-integrated differential cross sections with respect to the Bjorken scaling variable x. These results provide the first high-statistics direct measurements of nuclear effects in neutrino scattering using different targets in the same neutrino beam. Measured cross section ratios exhibit a relative depletion at low x and enhancement at large x. Both become more pronounced as the nucleon number of the target nucleus increases. The data are not reproduced by GENIE, a conventional neutrino-nucleus scattering simulation, or by the alternative models for the nuclear dependence of inelastic scattering that are considered.
Aims.
The aim of this study is to explore the magnetic and flow properties of fully convective M dwarfs as a function of rotation period
P
rot
and magnetic Reynolds Re
M
and Prandlt numbers Pr
M
.
...Methods.
We performed three-dimensional simulations of fully convective stars using a star-in-a-box set-up. This set-up allows global dynamo simulations in a sphere embedded in a Cartesian cube. The equations of non-ideal magnetohydrodynamics were solved with the P
ENCIL
C
ODE
. We used the stellar parameters of an M5 dwarf with 0.21
M
⊙
at three rotation rates corresponding to rotation periods (
P
rot
) of 43, 61, and 90 days, and varied the magnetic Prandtl number in the range from 0.1 to 10.
Results.
We found systematic differences in the behaviour of the large-scale magnetic field as functions of rotation and Pr
M
. For the simulations with
P
rot
= 43 days and Pr
M
≤ 2, we found cyclic large-scale magnetic fields. For Pr
M
> 2, the cycles vanish and the field shows irregular reversals. In the simulations with
P
rot
= 61 days for Pr
M
≤ 2, the cycles are less clear and the reversal are less periodic. In the higher Pr
M
cases, the axisymmetric mean field shows irregular variations. For the slowest rotation case with
P
rot
= 90 days, the field has an important dipolar component for Pr
M
≤ 5. For the highest Pr
M
the large-scale magnetic field is predominantly irregular at mid-latitudes, with quasi-stationary fields near the poles. For the simulations with cycles, the cycle period length slightly increases with increasing Re
M
.
Standards for clinical trials for treating TB du Cros, P; Greig, J; Alffenaar, J-W C ...
The international journal of tuberculosis and lung disease,
12/2023, Letnik:
27, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.
A global panel of experts participated in ...a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
Magnetite (Fe3O4) films were grown on glass substrates by formation and condensation of complex of iron oxides in an agarose hydrogel. The obtained films were characterized by Fourier Transform ...Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), Room Temperature Mössbauer Spectroscopy (TMS), Vibrating Sample Magnetometry (VSM), Atomic Force Microscopy (AFM) and Voltage vs. Current measurements by the four-point method. FTIR and TGA measurements showed that some polymer chains of agarose remain linked to the surface of the magnetic particles of the films after heat treatment. SEM measurements showed that the films are composed by quasi spherical particles with sizes around 55nm. Mössbauer spectroscopy measurements showed two sextets with broaden lines, which were assigned to magnetite with a distributed particle size, and two doublets, which were assigned to superparamagnetic phases of magnetite. For the specific dimensions of the films prepared, measurements of Voltage vs. Current showed an ohmic behavior for currents between 0 and 200nA, with a resistance of 355kΩ.
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