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Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

Abstract Objective This study aimed to investigate the effect and possible underlying mechanisms of high-fat diet-induced obesity on spermatogenesis in male rats. Methods A total of 45 male rats were randomly divided into control (n = 15, normal diet) and obesity groups (n = 30, high-fat diet) and were fed for 16 weeks. Body weight and organ indexes were determined after sacrifice. Indicators of reproductive function, including sperm count, sperm motility, apoptosis of spermatogenic cells, and oxidative stress levels, were measured. Serum metabolic parameters and reproductive hormones were also assayed. Results Compared with the control group, epididymal sperm motility in the obese rats was significantly decreased (P 0.05). Results Nutritional obesity can damage spermatogenesis in male rats due to long-term effects on spermatogenesis.

Nicotine and nicotinic acetylcholine receptors (nAChRs) are considered to be involved in lung cancer risk, onset and progression, but their precise physiological roles in these contexts remain unclear. Our previous studies suggested that α5-nAChR mediates nicotine-induced lung cancer cell proliferation, migration, and invasion in vitro. In this study, we aimed to determine the role of α5-nAChR in the development and progression of non-small cell lung cancer (NSCLC). Our microarray results reveal that knockdown of the CHRNA5 gene encoding α5-nAChR significantly modulates key pathways including the cell cycle, DNA replication, pathway in cancer. α5-nAChR knockdown in cultured A549 cells affected cell cycle distribution, apoptosis, and cyclin expression. In vivo, α5-nAChR silencing inhibited the growth of lung tumors, especially in the context of nicotine exposure. Importantly, α5-nAChR expression in patient tumors correlated with the primary T stage, N stage, and reduced survival time. These results reveal that α5-nAChR silencing inhibits the progression of nicotine-related NSCLC, making this receptor a potential pharmacological target for the treatment of nicotine-related lung carcinogenesis.

Active galactic nuclei (AGN) light curves observed with different wave bands show that the variability in longer wavelength bands lags the variability in shorter wavelength bands. Measuring these lags, or reverberation mapping, is used to measure the radial temperature profile and extent of AGN disks, typically with a reprocessing model that assumes X-rays are the main driver of the variability in other wavelength bands. To demonstrate how this reprocessing works with realistic accretion disk structures, we use 3D local shearing box multifrequency radiation magnetohydrodynamic simulations to model the UV-emitting region of an AGN disk, which is unstable to the magnetorotational instability and convection. At the same time, we inject hard X-rays (>1 keV) into the simulation box to study the effects of X-ray irradiation on the local properties of the turbulence and the resulting variability of the emitted UV light curve. We find that disk turbulence is sufficient to drive intrinsic variability in emitted UV light curves and that a damped random walk model is a good fit to this UV light curve for timescales >5 days. Meanwhile, X-ray irradiation has negligible impact on the power spectrum of the emitted UV light curve. Furthermore, the injected X-ray and emitted UV light curves are only correlated if there is X-ray variability on timescales >1 day, in which case we find a correlation coefficient r = 0.34. These results suggest that if the opacity for hard X-rays is scattering dominated as in the standard disk model, hard X-rays are not the main driver of reverberation signals.

Quasar feedback is a key ingredient in shaping galaxy evolution. A rare population of extremely red quasars (ERQs) at z = 2−3 are often associated with high-velocity [O iii ] λ 5008 outflows and may represent sites of strong feedback. In this paper, we present an X-ray study of 50 ERQs to investigate the link between the X-ray and outflow properties of these intriguing objects. Using hardness ratio analysis, we confirm that the ERQs are heavily obscured systems with gas column density reaching N _H = 10 ^23−24 cm ^−2 . We identify 20 X-ray-nondetected ERQs at high mid-infrared (MIR) luminosities of ν L _ν _,6 _ μ _m ≳ 3 × 10 ^46 erg s ^−1 . By stacking the X-ray observations, we find that the nondetected ERQs are on average underluminous in X-rays by a factor of ∼10 for their MIR luminosities. We consider such X-ray weakness to be due to both heavy gas absorption and intrinsic factors. Moreover, we find that the X-ray-weak sources also display higher-velocity outflows. One option to explain this trend is that weaker X-rays facilitate more vigorous line-driven winds, which then accelerate the [O iii ]-emitting gas to kiloparsec scales. Alternatively, super-Eddington accretion could also lead to intrinsic X-ray weakness and more powerful continuum-driven outflow.

We use the Athena++ Monte Carlo (MC) radiation transfer module to postprocess simulation snapshots from nonrelativistic Athena++ radiation magnetohydrodynamic (RMHD) simulations. These simulations were run using a gray (frequency-integrated) approach but were also restarted and ran with a multigroup approach that accounts for Compton scattering with a Kompaneets operator. These simulations produced moderately super-Eddington accretion rates onto a 6.62 M _⊙ black hole. Since we only achieve inflow equilibrium out to 20–25 gravitational radii, we focus on the hard X-ray emission. We provide a comparison between the MC and RMHD simulations, showing that the treatment of Compton scattering in the gray RMHD simulations underestimates the gas temperature in the funnel regions above and below the accretion disk. In contrast, the restarted multigroup snapshots provide a treatment for the radiation field that is more consistent with the MC calculations, and result in postprocessed spectra with harder X-ray emission compared to their gray snapshot counterparts. We characterize these MC postprocessed spectra using commonly employed phenomenological spectral fitting models. We also attempt to fit our MC spectra directly to observations of the ultraluminous X-ray source (ULX) NGC 1313 X-1, finding best-fit values that are competitive to phenomenological model fits, indicating that first principle models of super-Eddington accretion may adequately explain the observed hard X-ray spectra in some ULX sources.

The rising part of a tidal disruption event light curve provides unique insight into early emission and the onset of accretion. Various mechanisms are proposed to explain the pre-peak emission, including shocks from debris interaction and reprocessing of disk emission. We study the pre-peak emission and its influence on the gas circularization by a series of gray radiation hydrodynamic simulations with varying black hole mass. We find that, given a super-Eddington fallback rate of $10{\dot{M}}_{\mathrm{Edd}}$ , the stream–stream collision can occur multiple times and drive strong outflows of up to $9{\dot{M}}_{\mathrm{Edd}}$ . By dispersing gas to ≳100 r _s , the outflow can delay gas circularization and leads to sub-Eddington accretion rates during the first few stream–stream collisions. The stream–stream collision shock and circularization shock can sustain a luminosity of ∼10 ^44 erg s ^−1 for days. The luminosity is generally sub-Eddington and shows a weak correlation with accretion rate at early times. The outflow is optically thick, yielding a reprocessing layer with a size of ∼10 ^14 cm and photospheric temperature of ∼4 × 10 ^4 K.

Massive stars may form in or be captured into active galactic nuclei (AGN) disks. Recent 1D studies employing stellar-evolution codes have demonstrated the potential for rapid growth of such stars through accretion up to a few hundred solar masses. We perform 3D radiation hydrodynamic simulations of moderately massive stars’ envelopes in order to determine the rate and critical radius R _crit of their accretion process in an isotropic gas-rich environment in the absence of luminosity-driven mass loss. We find that in the “fast-diffusion” regime where characteristic radiative diffusion speed c / τ is faster than the gas sound speed c _s , the accretion rate is suppressed by feedback from gravitational and radiative advection energy flux, in addition to the stellar luminosity. Alternatively, in the “slow-diffusion” regime where c / τ < c _s , due to adiabatic accretion, the stellar envelope expands quickly to become hydrostatic and further net accretion occurs on thermal timescales in the absence of self-gravity. When the radiation entropy of the medium is less than that of the star, however, this hydrostatic envelope can become more massive than the star itself. Within this subregime, the self-gravity of the envelope excites runaway growth. Applying our results to realistic environments, moderately massive stars (≲100 M _⊙ ) embedded in AGN disks typically accrete in the fast-diffusion regime, leading to a reduction of steady-state accretion rate 1–2 orders of magnitudes lower than expected by previous 1D calculations and R _crit smaller than the disk scale height, except in the opacity window at temperature T ∼ 2000 K. Accretion in slow diffusion regime occurs in regions with very high density ρ ≳ 10 ^−9 g cm ^−3 , and needs to be treated with caution in 1D long-term calculations.

Turbulence is crucial for protoplanetary disk dynamics, and vertical shear instability (VSI) is a promising mechanism in outer disk regions to generate turbulence. We use the Athena++ radiation module to study VSI in full and transition disks, accounting for radiation transport and stellar irradiation. We find that the thermal structure and cooling timescale significantly influence VSI behavior. The inner rim location and radial optical depth affect disk kinematics. Compared with previous vertically isothermal simulations, our full disk and transition disks with small cavities have a superheated atmosphere and cool midplane with long cooling timescales, which suppresses the corrugation mode and the associated meridional circulation. This temperature structure also produces a strong vertical shear at τ _* = 1, producing an outgoing flow layer at τ _* < 1 on top of an ingoing flow layer at τ _* ∼ 1. The midplane becomes less turbulent, while the surface becomes more turbulent with effective α reaching ∼10 ^−2 at τ _* ≲ 1. This large surface stress drives significant surface accretion, producing substructures. Using temperature and cooling time measured/estimated from radiation-hydro simulations, we demonstrate that less computationally intensive simulations incorporating simple orbital cooling can almost reproduce radiation-hydro results. By generating synthetic images, we find that substructures are more pronounced in disks with larger cavities. The higher velocity dispersion at the gap edge could also slow particle settling. Both properties are consistent with recent near-IR and Atacama Large Millimeter/submillimeter Array (ALMA) observations. Our simulations predict that regions with significant temperature changes are accompanied by significant velocity changes, which can be tested by ALMA kinematics/chemistry observations.

We investigate the dynamical interaction between cosmic rays (CRs) and the multiphase interstellar medium (ISM) using numerical magnetohydrodynamic (MHD) simulations with a two-moment CR solver and TIGRESS simulations of star-forming galactic disks. We previously studied the transport of CRs within TIGRESS outputs using a “postprocessing” approach, and we now assess the effects of the MHD backreaction to CR pressure. We confirm our previous conclusion that there are three quite different regimes of CR transport in multiphase ISM gas, while also finding that simulations with “live MHD” predict a smoother CR pressure distribution. The CR pressure near the midplane is comparable to other pressure components in the gas, but the scale height of CRs is far larger. Next, with a goal of understanding the role of CRs in driving galactic outflows, we conduct a set of controlled simulations of the extraplanar region above z = 500 pc, with imposed boundary conditions flowing from the midplane into this region. We explore a range of thermal and kinematic properties for the injected thermal gas, encompassing both hot, fast-moving outflows, and cooler, slower-moving outflows. The boundary conditions for CR energy density and flux are scaled from the supernova rate in the underlying TIGRESS model. Our simulations reveal that CRs efficiently accelerate extraplanar material if the latter is mostly warm/warm-hot gas, in which CRs stream at the Alfvén speed, and the effective sound speed increases as density decreases. In contrast, CRs have very little effect on fast, hot outflows where the Alfvén speed is small, even when the injected CR momentum flux exceeds the injected MHD momentum flux.

In this paper, we review our current understanding of the outer envelope structures of massive stars based on three-dimensional (3D) radiation hydrodynamic simulations. We briefly summarize the fundamental issues in constructing hydrostatic one-dimensional (1D) stellar evolution models when stellar luminosity approaches the Eddington value. Radiation hydrodynamic simulations in 3D covering the mass range from 13M⊙ to 80M⊙ always find a dynamic envelope structure with the time-averaged radial profiles matching 1D models with an adjusted mixing-length parameter when convection is subsonic. Supersonic turbulence and episodic mass loss are generally found in 3D models when stellar luminosity is super-Eddington locally due to the opacity peaks and convection being inefficient. Turbulent pressure plays an important role in supporting the outer envelope, which makes the photosphere more extended than predictions from 1D models. Massive star lightcurves are always found to vary with a characteristic timescale consistent with the thermal time scale at the location of the iron opacity peak. The amplitude of the variability as well as the power spectrum can explain the commonly observed stochastic low-frequency variability of mass stars observed by TESS over a wide range of parameters in an HR diagram. The 3D simulations can also explain the ubiquitous macro-turbulence that is needed for spectroscopic fitting in massive stars. Implications of 3D simulations for improving 1D stellar evolution models are also discussed.

The outer envelopes of massive ( M ≳ 10 M _⊙ ) stars exhibit large increases in opacities from forests of lines and ionization transitions (particularly from iron and helium) that trigger near-surface convection zones. One-dimensional (1D) models predict density inversions and supersonic motions that must be resolved with computationally intensive three-dimensional (3D) radiation hydrodynamic (RHD) modeling. Only in the last decade have computational tools advanced to the point where ab initio 3D models of these turbulent envelopes can be calculated, enabling us to present five 3D RHD Athena++ models (four previously published and one new 13 M _⊙ model). When convective motions are subsonic, we find excellent agreement between 3D and 1D velocity magnitudes, stellar structure, and photospheric quantities. However, when convective velocities approach the sound speed, hydrostatic balance fails as the turbulent pressure can account for 80% of the force balance. As predicted by Henyey, we show that this additional pressure support leads to a modified temperature gradient, which reduces the superadiabaticity where convection is occurring. In addition, all five models display significant overshooting from the convection in the Fe convection zone. As a result, the turbulent velocities at the surface are indicative of those in the Fe zone. There are no confined convection zones as seen in 1D models. In particular, helium convection zones seen in 1D models are significantly modified. Stochastic low-frequency brightness variability is also present in the 13 M _⊙ model with comparable amplitude and characteristic frequency to observed stars.

The variability of quasar light curves can be used to study the structure of quasar accretion disks. For example, continuum reverberation mapping uses delays between variability in short and long wavelength bands ( short lags) to measure the radial extent and temperature profile of the disk. Recently, a potential reverse lag, where variations in shorter wavelength bands lag the longer wavelength bands at the much longer viscous timescale, was detected for Fairall 9. Inspired by this detection, we derive a timescale for these long negative lags from fluctuation propagation models and recent simulations. We use this timescale to forecast our ability to detect long lags using the Vera Rubin Legacy Survey of Space and Time (LSST). After exploring several methods, including the interpolated cross-correlation function, a Von-Neumann estimator, javelin , and a maximum-likelihood Fourier method, we find that our two main methods, javelin and the maximum-likelihood method, can together detect long lags of up to several hundred days in mock LSST light curves. Our methods work best on proposed LSST cadences with long season lengths, but can also work for the current baseline LSST cadence, especially if we add observations from other optical telescopes during seasonal gaps. We find that LSST has the potential to detect dozens to hundreds of additional long lags. Detecting these long lags can teach us about the vertical structure of quasar disks and how it scales with different quasar properties.

Stream–stream collision may be an important prepeak energy dissipation mechanism in tidal disruption events (TDEs). We perform local three-dimensional radiation hydrodynamic simulations in a wedge geometry including the gravity to study stream self-crossing with an emphasis on resolving the collision and following the subsequent outflow. We find that the collision can contribute to prepeak optical emissions by converting ≳5% of the stream kinetic energy to radiation, yielding prompt emission of ∼10 ^42−44 erg s ^−1 . The radiative efficiency is sensitive to stream mass fallback rates and strongly depends on the downstream gas optical depth. Even for a sub-Eddington (10%) mass fallback rate, the strong radiation pressure produced in the collision can form a local super-Eddington region near the collision site, where a fast, aspherical outflow is launched. A higher mass fallback rate usually leads to more optically thick outflow and lower net radiative efficiency. For $\dot{M}\gtrsim 0.1{\dot{M}}_{\mathrm{Edd}}$ , the estimated photosphere size of the outflow can expand by 1–2 orders of magnitude, reaching ∼10 ^14 cm. The average gas temperature at this photospheric surface is a few × 10 ^4 K, roughly consistent with inferred prepeak photosphere properties for some optical TDEs. We find that the dynamics is sensitive to the collision angle and radius, but the radiative efficiency or outflow properties show more complex dependency than is often assumed in ballistic models.

We report the detection of a long-timescale negative lag, where the blue bands lag the red bands, in the nearby Seyfert 1 galaxy Fairall 9, with two independent methods. Active Galactic Nuclei (AGNs) light curves show variability over a wide range of timescales. By measuring time lags between different wavelengths, the otherwise inaccessible structure and kinematics of the accretion disk can be studied. One common approach, reverberation mapping, quantifies the continuum and line lags moving outward through the disk at the light-travel time, revealing the size and temperature profile of the disk. Inspired by numerical simulations, we expect longer lags to exist in AGN light curves that travel inward on longer timescales, tracing the accretion process itself. By analyzing AGN light curves in both temporal and frequency space, we report the detection of long-timescale lags (∼−70 days) in Fairall 9 that propagate in the opposite direction to the reverberation lag. The short continuum lag (

We extend the general-relativistic magnetohydrodynamics (GRMHD) capabilities of Athena++ to incorporate radiation. The intensity field in each finite-volume cell is discretized in angle, with explicit transport in both space and angle properly accounting for the effects of gravity on null geodesics, and with matter and radiation coupled in a locally implicit fashion. Here we describe the numerical procedure in detail, verifying its correctness with a suite of tests. Motivated in particular by black hole accretion in the high-accretion-rate, thin-disk regime, we demonstrate the application of the method to this problem. With excellent scaling on flagship computing clusters, the port of the algorithm to the GPU-enabled AthenaK code now allows the simulation of many previously intractable radiation-GRMHD systems.

We perform 3D radiation hydrodynamic local shearing-box simulations to study the outcome of gravitational instability (GI) in optically thick active galactic nuclei (AGNs) accretion disks. GI develops when the Toomre parameter Q _T ≲ 1, and may lead to turbulent heating that balances radiative cooling. However, when radiative cooling is too efficient, the disk may undergo runaway gravitational fragmentation. In the fully gas-pressure-dominated case, we confirm the classical result that such a thermal balance holds when the Shakura–Sunyaev viscosity parameter ( α ) due to the gravitationally driven turbulence is ≲0.2, corresponding to dimensionless cooling times Ω t _cool ≳ 5. As the fraction of support by radiation pressure increases, the disk becomes more prone to fragmentation, with a reduced (increased) critical value of α (Ω t _cool ). The effect is already significant when the radiation pressure exceeds 10% of the gas pressure, while fully radiation-pressure-dominated disks fragment at t _cool ≲ 50 Ω ^−1 . The latter translates to a maximum turbulence level α ≲ 0.02, comparable to that generated by magnetorotational instability. Our results suggest that gravitationally unstable ( Q _T ∼ 1) outer regions of AGN disks with significant radiation pressure (likely for high/near-Eddington accretion rates) should always fragment into stars, and perhaps black holes.

Observations indicate that turbulent motions are present on most massive star surfaces. Starting from the observed phenomena of spectral lines with widths that are much larger than their thermal broadening (e.g., micro- and macroturbulence), and considering the detection of stochastic low-frequency variability (SLFV) in the Transiting Exoplanet Survey Satellite photometry, these stars clearly have large-scale turbulent motions on their surfaces. The cause of this turbulence is debated, with near-surface convection zones, core internal gravity waves, and wind variability being proposed. Our 3D gray radiation hydrodynamic (RHD) models previously characterized the convective dynamics of the surfaces, driven by near-surface convection zones, and provided reasonable matches to the observed SLFV of the most luminous massive stars. We now explore the complex emitting surfaces of these 3D RHD models, which strongly violate the 1D assumption of a plane-parallel atmosphere. By post-processing the gray RHD models with the Monte Carlo radiation transport code Sedona , we synthesize stellar spectra and extract information from the broadening of individual photospheric lines. The use of Sedona enables the calculation of the viewing angle and temporal dependence of spectral absorption line profiles. By combining uncorrelated temporal snapshots together, we compare the turbulent broadening from the 3D RHD models to the thermal broadening of the extended emitting region, showing that our synthesized spectral lines closely resemble the observed macroturbulent broadening from similarly luminous stars. More generally, the new techniques that we have developed will allow for systematic studies of the origins of turbulent velocity broadening from any future 3D simulations.

We present global 3D radiation magnetohydrodynamic simulations of accretion onto a 6.62 solar-mass black hole, with quasi-steady-state accretion rates reaching 0.016–0.9 times the critical accretion rate, which is defined as the accretion rate for powering the Eddington luminosity, assuming a 10% radiative efficiency, in three different runs. The simulations show no sign of thermal instability over hundreds of thermal timescales at 10 r _g . The energy dissipation occurs close to the mid-plane in the near-critical runs and near the disk surface in the low–accretion rate run. The total radiative luminosity inside ∼20 r _g is about 1%–30% of the Eddington limit, with radiative efficiencies of about 6% and 3%, respectively, in the sub- and near-critical accretion regimes. In both cases, self-consistent turbulence generated by the magnetorotational instability leads to angular momentum transfer, and the disk is supported by magnetic pressure. Outflows from the central low-density funnel, with a terminal velocity of ∼0.1 c , are seen only in the near-critical runs. We conclude that these magnetic pressure–dominated disks are thermally stable and thicker than the α disk, and that the effective temperature profiles are much flatter than those in the α disks. The magnetic pressures of these disks are comparable within an order of magnitude to the previous analytical magnetic pressure–dominated disk model.

Objective: The treatment methods for the failed internal fixation in elderly patients suffering from several osteoporostic fractures are still inconclusive. We aimed to evaluate the clinical effects of endoprosthetic replacement for failure treatment of intertrochanteric fracture. Methodology: A total of 13 patients with failed internal fixation for intertrochanteric fracture were collected between January 2002 and October 2009. All of them were treated with endoprosthetic replacement and followed up till October 2010. Four of them received total hip replacement and the remained nine received artificial bipolar femoral head replacement. Clinical and functional outcomes of patients were assessed. Results: Of 13 patients, nine were females and four were males with the mean age of 76.5 years (SD, 11.7, range, 58-92 years) at the time of fracture. The average time of operation and follow-up was 124 minutes (89-187minutes) and 31 months (14-68 months), respectively. The average blood loss during the operation was 631 ml (450-1560 ml). All patients showed good pain relief and functional improvement. Final postoperative Harris and WOMAC scores were significantly improved from pre-operative levels (P < 0.05). Only five patients showed operative complications. Conclusions: Our finding indicated that endoprosthetic replacement is an effective salvage procedure for failed internal fixation of intertrochanteric fracture in elderly patients with effective pain relief and functional improvement as well as few serious complications. [ABSTRACT FROM AUTHOR]

Objective: The treatment methods for the failed internal fixation in elderly patients suffering from several osteoporostic fractures are still inconclusive. We aimed to evaluate the clinical effects of endoprosthetic replacement for failure treatment of intertrochanteric fracture., Methodology: A total of 13 patients with failed internal fixation for intertrochanteric fracture were collected between January 2002 and October 2009. All of them were treated with endoprosthetic replacement and followed up till October 2010. Four of them received total hip replacement and the remained nine received artificial bipolar femoral head replacement. Clinical and functional outcomes of patients were assessed., Results: Of 13 patients, nine were females and four were males with the mean age of 76.5 years (SD, 11.7, range, 58-92 years) at the time of fracture. The average time of operation and follow-up was 124 minutes (89-187minutes) and 31 months (14-68 months), respectively. The average blood loss during the operation was 631 ml (450-1560 ml). All patients showed good pain relief and functional improvement. Final post-operative Harris and WOMAC scores were significantly improved from pre-operative levels (P<0.05). Only five patients showed operative complications., Conclusions: Our finding indicated that endoprosthetic replacement is an effective salvage procedure for failed internal fixation of intertrochanteric fracture in elderly patients with effective pain relief and functional improvement as well as few serious complications.