Summary
Abaloparatide (ABL) is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. ...However, real-world data regarding its long-term safety and tolerability in large sample population are incomplete. We evaluated abaloparatide-associated safety signals by data mining of the FDA pharmacovigilance database.
Introduction
We investigated 33,480(0.14%) ABL-related adverse events (AEs) through data mining of Food and Drug Administration Adverse Event Reporting System (FAERS) retrospectively.
Methods
Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to quantify the signals of ABL-related AEs from 2017Quarter2 to 2022.Serious and non-serious cases were compared by Mann-Whitney
U
test or Chi-squared (
χ
2
) test.
Results
We collected 8,470,497 reports from the FAERS database, including 11,487 reports defined ABL as the primary suspected (PS) drug. Additionally, 36.16% of the reports were submitted by healthcare professionals (
n
=4154), compared to 62.26% reported by consumers (
n
=7140). A total 99 signals simultaneously conforming to four algorithms were detected, among which, 35 signals were identified as unexpected signals. Such as growing pains (
n
=13), waist circumference increased (
n
=21), sensory disturbance (
n
=103), tinnitus (
n
=65), visual acuity reduced (
n
=54), blood alkaline phosphatase increased (
n
=61), and hair growth abnormal (
n
=13). Patient age (
p
< 0.001) might be associated with an increased risk of AEs severity. The most common timeframe for AE occurrence was 0–7 days.
Conclusion
Our study provided a deeper and broader understanding of abaloparatide’s safety profiles, which would help healthcare professionals to mitigate the risk of AEs in clinical practice, a low number of unexpected AEs supporting ongoing additional pharmacovigilance.
Fluidization is widely used in industries and has been extensively studied, either experimentally or theoretically, in the past decades. In recent years, a coupled simulation approach of discrete ...element method (DEM) and computational fluid dynamics (CFD) has been successfully developed to study the gas–solid flow and heat transfer in fluidization at a particle scale. However, to date, such studies mainly deal with spherical particles. The effect of particle shape on fluidization is recognized but not properly quantified. In this paper, the CFD–DEM approach is extended to consider the fluidization of ellipsoidal particles. In the simulation, particles used are either oblate or prolate, with aspect ratios varying from very flat (aspect ratio=0.25) to elongated (aspect ratio=3.5), representing cylinder-type and disk-type shaped particles, respectively. The commonly used correlations to determine the fluid drag force acting on a non-spherical particle are compared first. Then the model is verified in terms of solid flow patterns. The effect of aspect ratio on the flow pattern, the relationship between pressure drop and gas superficial velocity, and microscopic parameters such as coordination number, particle orientation and force structure are investigated. It is shown that particle shape affects bed permeability and the minimum fluidization velocity significantly. The coordination number generally increases with aspect ratio deviating from 1.0. The analysis of particle orientations shows that the bed structures for ellipsoids are not random as that for spheres. Oblate particles prefer facing upward or downward while prolate particles prefer horizontal orientation. Spheres have the largest particle–particle contact force and fluid drag force under the comparable conditions. With aspect ratio deviating from 1.0, particle–particle interaction and fluid drag become relatively weak. The proposed model shows a promising method in examining the effect of particle shape on different flow behaviour in gas fluidization.
► The CFD–DEM approach is extended to describe the fluidization of ellipsoidal particles. ► The effect of aspect ratio on the flow pattern, the relationship between pressure drop and gas superficial velocity. ► Microscopic parameters such as coordination number, particle orientation and force structure are investigated. ► It is shown that with aspect ratio deviating from 1.0, the particle–particle interaction and fluid drag forces decrease.
Meaningful intercultural interactions are important to the achievement of today's educational goals, global citizenship and intercultural competence in particular. However, understanding of ...intercultural interactions between local and international students in classroom settings remains limited. There are few studies that simultaneously examine the way in which the learning environment is designed by the instructor to facilitate intercultural interactions and the way it is actually experienced by students of various cultural backgrounds. This study sought to unpack the complexities of intercultural interactions in Chinese classrooms. Data were collected from student and teacher interviews and classroom observations. Seven modes of meaningful interactions were identified, and four pairs of elements (i.e. openness and trust, structure and space, empowerment and confidence, and modelling and amplifying) were found to be essential. The distinct dynamics of Chinese classrooms are also highlighted.
ABSTRACT It is important to study the fine structures of solar filaments with high-resolution observations, since it can help us understand the magnetic and thermal structures of the filaments and ...their dynamics. In this paper, we study a newly formed filament located inside the active region NOAA 11762, which was observed by the 1.6 m New Solar Telescope at Big Bear Solar Observatory from 16:40:19 UT to 17:07:58 UT on 2013 June 5. As revealed by the H filtergrams, cool material is seen to be injected into the filament spine with a speed of 5-10 km s−1. At the source of the injection, brightenings are identified in the chromosphere, which are accompanied by magnetic cancellation in the photosphere, implying the importance of magnetic reconnection in replenishing the filament with plasmas from the lower atmosphere. Counter-streamings are detected near one endpoint of the filament, with the plane-of-the-sky speed being 7-9 km s−1 in the H red-wing filtergrams and 9-25 km s−1 in the blue-wing filtergrams. The observations are indicative that this active region filament is supported by a sheared arcade without magnetic dips, and the counter-streamings are due to unidirectional flows with alternative directions, rather than due to the longitudinal oscillations of filament threads as in many other filaments.
The objective of the Apollon 10 PW project is the generation of 10 PW peak power pulses of 15 fs at $1~\text{shot}~\text{min}^{-1}$. In this paper a brief update on the current status of the Apollon ...project is presented, followed by a more detailed presentation of our experimental and theoretical investigations of the temporal characteristics of the laser. More specifically the design considerations as well as the technological and physical limitations to achieve the intended pulse duration and contrast are discussed.
This study investigates impacts of a wave farm on waves, currents and coastal morphology adjacent to the wave farm, which is located in the Southwest of England (the Wave Hub). In this study, we ...focus on the interaction between waves and tides due to the presence of the wave farm and its effects on wave radiation stresses, bottom shear stresses and consequently on the sediment transport and the coast adjacent to the wave farm, using an integrated numerical modelling system. The modelling system consists of the near-shore wave model SWAN, the ocean circulation model ROMS and a sediment transport model for morphological evolution. The results show that tidal elevation and tidal currents can have a significant effect on waves and that tidal forcing and waves have a significant effect on bottom shear stresses. Waves can impact on the processes related to the bottom boundary layer and mixing intensity in the water column. The wave farm has an impact on the gradients of radiation shear stresses and bottom shear stresses that modify current speeds and wave heights, which in turn impact on the near-shore sediment transport and the resulting morphological changes. Bed load transport rates show a decrease when the wave farm is present, even during storm conditions. The results highlight the importance of the interactions between waves and tides when modelling coastal morphology with presence of wave energy devices.
Abstract
We conducted observations of multiple HC
3
N (
J
= 10−9, 12−11, and 16−15) lines and the N
2
H
+
(
J
= 1−0) line toward a large sample of 61 ultracompact (UC) H
ii
regions, through the ...Institut de Radioastronomie Millmétrique 30 m and the Arizona Radio Observatory 12 m telescopes. The N
2
H
+
J
= 1−0 line is detected in 60 sources and HC
3
N is detected in 59 sources, including 40 sources with three lines, 9 sources with two lines, and 10 sources with one line. Using the rotational diagram, the rotational temperature and column density of HC
3
N were estimated toward sources with at least two HC
3
N lines. For 10 sources with only one HC
3
N line, their parameters were estimated, taking one average value of
T
rot
. For N
2
H
+
, we estimated the optical depth of the N
2
H
+
J
= 1−0 line, based on the line intensity ratio of its hyperfine structure lines. Then the excitation temperature and column density were calculated. When combining our results in UC H
ii
regions and previous observation results on high-mass starless cores, the
N
(HC
3
N)/
N
(N
2
H
+
) ratio clearly increases from the region stage. This means that the abundance ratio changes with the evolution of high-mass star-forming regions (HMSFRs). Moreover, positive correlations between the ratio and other evolutionary indicators (dust temperature, bolometric luminosity, and luminosity-to-mass ratio) are found. Thus we propose the ratio of
N
(HC
3
N)/
N
(N
2
H
+
) as a reliable chemical clock of HMSFRs.
The thermophysical properties of liquid Zr-Fe alloys were experimentally measured by an electrostatic levitation technique. A series of undercoolings from 45 K to 410 K were achieved for these liquid ...alloys in the natural radiation cooling process. Since the experiments were conducted in high-vacuum and containerless conditions, the ratio of the specific heat to the hemispherical emissivity was deduced and showed a quadratic relationship with temperature. For the eutectic Zr
76
Fe
24
alloy, the hypercooling of 306 K and hemispherical emissivity were derived theoretically due to its low liquidus temperature and scarce volatilization. Through digital image processing, the alloy densities were measured, and the results depended linearly on temperature over a wide temperature range covering both superheated and undercooled liquid states. The absolute value of the temperature coefficient tended to increase with increasing Fe contents, indicating that the liquid density sensitivity increased with increasing Fe contents. The surface tension and viscosity were also determined by a drop oscillation method under the electrostatic levitation condition.
The solidification mechanism of hyperperitectic Ti60Ni40 alloy was systematically investigated by using the electrostatic levitation (ESL) technique, and the maximum undercooling achieved was up to ...373 K (0.25 TL). When the undercooling is below a threshold of 281 K, typical peritectic solidification prevailed within the levitated liquid alloy, and the double recalescence processes were observed by a high-speed camera. In this case, the primary TiNi compound preferentially grew as well-defined dendrites, and the interdendritic Ti2Ni phase was subsequently produced by the peritectic reaction and transformation. TEM analyses showed that an incomplete martensitic transformation occurs in the primary TiNi phase, which results in the complicated structure of B19’ martensite and R-phase. Once the undercooling exceeded 281 K, the coupled-growth mode between TiNi and Ti2Ni compounds was induced, leading to the lamellar and anomalous eutectic-like microstructures. The enhancement of undercooling promoted the migration speed of liquid-solid interface in both typical peritectic solidification and metastable coupled-growth modes, but it exhibited an abrupt reduction in critical undercooling. The microscopic hardness of the primary TiNi phase processed by ESL was 48.1% higher than that of the Ti60Ni40 master alloy, while it increased by 29.0% for the peritectic Ti2Ni phase. These indicated that the peritectic-type superalloys with advanced performances could be designed by modulating the solidification process and solid solubility through different undercoolings.
Display omitted
•Liquid-solid interface migration is in-situ observed.•Eutectic-like lamellar structure is obtained by the “coupled-growth” of hyperperitectic alloy.•Two different solidification mechanisms of hyperperitectic alloy is sufficiently clarified.•Intermediate phase (R-phase) of martensitic transformation is found in TiNi phase.•Relationship between mechanical property and microstructure is established.
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