Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system.

BACKGROUND: Upadacitinib was approved to treat rheumatoid arthritis, psoriasis, ulcerative colitis, ankylosing spondylitis, and atopic dermatitis. This study assessed the adverse events (AEs) associated with upadacitinib by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of upadacitinib-associated AEs. RESULTS: A total of 3,837,420 reports of AEs were collected from the FAERS database, of which 4494 reports were identified with upadacitinib as the "primary suspect (PS)". Upadacitinib-induced AEs occurrence targeted 27 system organ clases (SOCs). A total of 200 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected significant AEs, such as arthralgia, musculoskeletal stiffness, diverticulitis, and cataract might also occur. The median onset time of upadacitinib-associated AEs was 65 days (interquartile range [IQR] 21-182 days), and most of the onsets occurred within the first 1, 2, 3, and 4 months after initiation of upadacitinib. CONCLUSION: This study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of upadacitinib.

Note on the instability mechanism of gravity-driven unsaturated slow flow in porous media.

A capillary tube model reveals that the surface tension at the air-water interface cannot cause the instability of gravity-driven unsaturated slow flow in sandy soils.

An analytical model for the growth and migration of a transverse dune.

The growth and migration speed formulae for a 2-d transverse dune are derived under the assumptions of shape similarity, the near surface airflow independent of height, and the 100% sand trapping efficiency of lee face during dune evolution. Although very simple, this analytical model can quantificationally reflect the field investigations of barchan migrations and the chronological data of mega-dune growth.

Unsteady aeolian saltation.

Wind velocity and saltating grain count rate in the natural unsteady aeolian sediment transport are synchronously measured on the gently inclined windward slope of one horn of a large barchan. The obtained time series of these two variables are analyzed, by using the improved complete ensemble empirical mode decomposition and wavelet coherence, to investigate the wind-saltation interactions at different timescales. It is found that the wind-saltation trend relation obeys the traditional low-order polynomial expressions, and saltation mode is roughly proportional to its corresponding wind mode if they are strongly correlated. As a conclusion, it is probable to partly predict instantaneous saltation activities near the surface by the empirical trend and effective modes of wind speed at a given height.

A theoretical interpretation of the "giant" dust particle conundrum.

The effects of electric force were used to interpret a well known conundrum about the long-term (or long-distance) dust transport in the atmosphere.

Intermittency of aeolian saltation.

Saltation motion of sand grains in a steady wind was measured using a high-speed camera at very high frequency in a wind tunnel. A Heaviside-type function was defined to quantificationally describe an inherent property of saltation, i.e. intermittency. Kurtosis and periodicity of state function are statistical manifestations of intermittency. In addition, the strong autocorrelation of time series of volume concentration clearly confirms that saltation is not a completely random process at the timescale of subsecond. Formation mechanism, especially turbulent structures responsible for intermittent saltation, remains to be revealed from the viewpoint of classical mechanics.

Forces on a saltating grain in air.

A wind tunnel experiment was performed to measure the trajectories of individual sand grains. Then, the acceleration given by the numerical differentiation was used to assess the relative importance of different external forces on a saltating sand grain in air. It is reconfirmed that the gravitational force and drag are the most important to grain motion. The lift also has certain influence. However, the present research does not support that the electrostatic force is significant.

Abrasion of yardangs.

A model for the collision between a sand grain and a body of yardang material is established by using the principles of classical mechanics. A new nondimensional parameter, the "abrasion number" A(n), is derived from the model. The volume removed per impact for different targets is proportional to A(n) approximately. As an indicator of the energy ratio of the impacting material to the target material, A(n) not only reflects the previous "abrasion law" but also introduces two dominant mechanical parameters, Young's modulus and yield stress. We propose A(n) to be a similarity criterion for abrasion experiments. The practicability of the model under natural conditions is examined by an example. It is concluded that the abrasion rates of yardangs in the western Qaidam basin, China, are 0.011-0.398 mm/yr in the period of 1986 to 2010 and remarkable abrasion events generally correspond with strong wind conditions. The model will be helpful for reconstructing the history of aeolian activities from the morphologies of yardangs in the arid regions on Mars.

Prognostic factors and outcome of resected patients with gastrointestinal stromal tumors of small intestine.

We document the clinical behavior of gastrointestinal stromal tumors (GISTs) of the small intestine and identify predictors for long-term disease-free survival (DFS) for small intestine GIST patients. From December 2001 to 2008, 114 consecutive patients with mesenchymal tumors involving the small intestine were enrolled. There were 54 male and 60 female (50.6%) patients. After a median follow-up period of 36 months (ranging from 12 to 96 months), recurrence was noted in 19 patients (16.7%) with a median time of 20 months (ranging from 7 to 50 months). There were 12 patients (10.5%) who died of GISTs with a median time from recurrence to death of 14 months (ranging from 8 to 22 months). Univariate analysis by log-rank test indicated that tumor size and mitotic activity were statistically significant for DFS (P = 0.001 and 0.036, respectively). Tumor size was the only significant predictive factor for DFS according to multivariate analysis (P = 0.006). Small tumor size, indicating low risk, predicted more favorable DFS of small intestine GIST patients who underwent curative resection.