Patient-reported outcomes 6 months after enhanced recovery after colorectal surgery.

BackgroundEnhanced recovery after surgery (ERAS) programs have been established as perioperative strategies associated with improved outcomes. However, intermediate and long-term patient-reported outcome data for patients undergoing ERAS interventions remain limited. We utilized an automated telephone survey 6 months post-colorectal surgery from patients who participated in an ERAS program to determine 6-month patient-reported outcomes and associated predictive factors.MethodsWe conducted a prospective observational study, using an automated telephone survey and researcher-administered telephone questionnaire 6 months after patients underwent abdominal colorectal surgery. Six-month significant outcomes were defined by persistent pain, hospital readmission, and patient satisfaction. Patients reporting these outcome variables were compared with patients who met none of these criteria. Additionally, analysis was performed to determine differences between patients that did and did not respond to the 6-month survey. A chi-square test was used to determine any relationship for categorical variables, a two independent sample t test for length of procedure/stay, and a Wilcoxon-Mann-Whitney test for pain scores.ResultsOne hundred fifty-four of 324 patients contacted 6 months after surgery completed the automated telephone survey (47.53%). There was no statistical difference between patient populations completing and not completing the survey. Hospital 6-month readmission was associated with patients with a diagnosis of cancer (P = .049) and with a longer mean length of index procedure (282 vs. 206 minutes, P = .006). Median 6-month pain scores were higher for patients that underwent an open procedure compared to laparoscopic (Z = - 2.06, P = .04).ConclusionsLong-term benefits of an ERAS program were mostly confirmed. Longer procedure time and patients with cancer correlated with an increased likelihood of hospital 6-month readmission, suggesting that perioperative outcomes in complex cancer patients need to be evaluated over a longer time frame. In addition, invasiveness of procedure continues to have a significant effect on pain scores even 6 months later

Heating and Turbulence Driving by Galaxy Motions in Galaxy Clusters

Using three-dimensional hydrodynamic simulations, we investigate heating and turbulence driving in an intracluster medium (ICM) by orbital motions of galaxies in a galaxy cluster. We consider Ng member galaxies on isothermal and isotropic orbits through an ICM typical of rich clusters. An introduction of the galaxies immediately produces gravitational wakes, providing perturbations that can potentially grow via resonant interaction with the background gas. When Ng^{1/2}Mg_11 < 100, where Mg_11 is each galaxy mass in units of 10^{11} Msun, the perturbations are in the linear regime and the resonant excitation of gravity waves is efficient to generate kinetic energy in the ICM, resulting in the velocity dispersion sigma_v ~ 2.2 Ng^{1/2}Mg_11 km/s. When Ng^{1/2}Mg_11 > 100, on the other hand, nonlinear fluctuations of the background ICM destroy galaxy wakes and thus render resonant excitation weak or absent. In this case, the kinetic energy saturates at the level corresponding to sigma_v ~ 220 km/s. The angle-averaged velocity power spectra of turbulence driven in our models have slopes in the range of -3.7 to -4.3. With the nonlinear saturation of resonant excitation, none of the cooling models considered are able to halt cooling catastrophe, suggesting that the galaxy motions alone are unlikely to solve the cooling flow problem.Comment: 12 pages including 3 figures, To appear in ApJ

Off-Center Mergers of Clusters of Galaxies and Nonequipartition of Electrons and Ions in Intracluster Medium

We investigate the dynamical evolution of clusters of galaxies and their observational consequences during off-center mergers, explicitly considering the relaxation process between ions and electrons in intracluster medium by N-body and hydrodynamical simulations. In the contracting phase a bow shock is formed between the two subclusters. The observed temperature between two peaks in this phase depends on the viewing angle even if the geometry of the system seems to be very simple like head-on collisions. Around the most contracting epoch, when we observe merging clusters nearly along the collision axis, they look like spherical relaxed clusters with large temperature gradients. In the expanding phase, spiral bow shocks occur. As in head-on mergers, the electron temperature is significantly lower than the plasma mean one especially in the post-shock regions in the expanding phase. When the systems have relatively large angular momentum, double-peak structures in the X-ray images can survive even after the most contracting epoch. Morphological features in both X-ray images and electron temperature distribution characteristic to off-center mergers are seriously affected by the viewing angle. When the clusters are observed nearly along the collision axis, the distribution of galaxies' line-of-sight (LOS) velocities is a good indicator of mergers. In the contracting phase, an negative kurtosis and a large skewness are expected for nearly equal mass collisions and rather different mass ones, respectively. To obtain statistically significant results, about 1000 galaxies' LOS velocities are required. For nearby clusters ($z<0.05$), large redshift surveys such as 2dF will enable us to study merger dynamics.Comment: 21 pages, 7 figures. Accepted for publication in Ap

Neutrinos and Gamma Rays from Galaxy Clusters

The next generation of neutrino and gamma-ray detectors should provide new insights into the creation and propagation of high-energy protons within galaxy clusters, probing both the particle physics of cosmic rays interacting with the background medium and the mechanisms for high-energy particle production within the cluster. In this paper we examine the possible detection of gamma-rays (via the GLAST satellite) and neutrinos (via the ICECUBE and Auger experiments) from the Coma cluster of galaxies, as well as for the gamma-ray bright clusters Abell 85, 1758, and 1914. These three were selected from their possible association with unidentified EGRET sources, so it is not yet entirely certain that their gamma-rays are indeed produced diffusively within the intracluster medium, as opposed to AGNs. It is not obvious why these inconspicuous Abell-clusters should be the first to be seen in gamma-rays, but a possible reason is that all of them show direct evidence of recent or ongoing mergers. Their identification with the EGRET gamma-ray sources is also supported by the close correlation between their radio and (purported) gamma-ray fluxes. Under favorable conditions (including a proton spectral index of 2.5 in the case of Abell 85, and sim 2.3 for Coma, and Abell 1758 and 1914), we expect ICECUBE to make as many as 0.3 neutrino detections per year from the Coma cluster of galaxies, and as many as a few per year from the Abell clusters 85, 1758, and 1914. Also, Auger may detect as many as 2 events per decade at ~ EeV energies from these gamma-ray bright clusters.Comment: Accepted for publication in Ap

Nonthermal Bremsstrahlung and Hard X-ray Emission from Clusters of Galaxies

We have calculated nonthermal bremsstrahlung (NTB) models for the hard X-ray (HXR) tails recently observed by BeppoSAX in clusters of galaxies. In these models, the HXR emission is due to suprathermal electrons with energies of about 10-200 keV. Under the assumption that the suprathermal electrons form part of a continuous spectrum of electrons including highly relativistic particles, we have calculated the inverse Compton (IC) extreme ultraviolet (EUV), HXR, and radio synchrotron emission by the extensions of the same populations. For accelerating electron models with power-law momentum spectra (N[p] propto p^{- mu}) with mu <~ 2.7, which are those expected from strong shock acceleration, the IC HXR emission exceeds that due to NTB. Thus, these models are only of interest if the electron population is cut-off at some upper energy <~1 GeV. Similarly, flat spectrum accelerating electron models produce more radio synchrotron emission than is observed from clusters if the ICM magnetic field is B >~ 1 muG. The cooling electron model produces vastly too much EUV emission as compared to the observations of clusters. We have compared these NTB models to the observed HXR tails in Coma and Abell 2199. The NTB models require a nonthermal electron population which contains about 3% of the number of electrons in the thermal ICM. If the suprathermal electron population is cut-off at some energy above 100 keV, then the models can easily fit the observed HXR fluxes and spectral indices in both clusters. For accelerating electron models without a cutoff, the electron spectrum must be rather steep >~ 2.9.Comment: Accepted for publication in the Astrophysical Journal. 10 pages with 5 embedded Postscript figures in emulateapj.sty. An abbreviated abstract follow

Merger shocks in galaxy clusters A665 and A2163 and their relation to radio halos

We present Chandra gas temperature maps for two hot, intermediate-redshift clusters A665 and A2163. Both show strong temperature variations in their central r=1 Mpc regions, naturally interpreted as product of the subcluster mergers. The A665 map reveals a shock in front of the cool core, while the temperature structure of A2163 is more complicated. On a larger linear scale, our data on A2163 indicate a radial temperature decline in agreement with earlier ASCA results, although the uncertainties are large. Both these clusters exhibit previously known synchrotron radio halos. Comparison of the radio images and the gas temperature maps indicates that radio emission predominantly comes from the hot gas regions, providing a strong argument in favor of the hypothesis that relativistic electrons are accelerated in merger shocks.Comment: Updated radio image for A2163, expanded introduction. ApJ in press. 8 pages, uses emulateapj.sty. Color version is at http://hea-www.harvard.edu/~maxim/papers/665.ps.gz (PS) or http://hea-www.harvard.edu/~maxim/papers/665.pdf (PDF

Gamma-Ray Background from Structure Formation in the Intergalactic Medium

The universe is filled with a diffuse and isotropic extragalactic background of gamma-ray radiation, containing roughly equal energy flux per decade in photon energy between 3 MeV-100 GeV. The origin of this background is one of the unsolved puzzles in cosmology. Less than a quarter of the gamma-ray flux can be attributed to unresolved discrete sources, but the remainder appears to constitute a truly diffuse background whose origin has hitherto been mysterious. Here we show that the shock waves induced by gravity during the formation of large-scale structure in the intergalactic medium, produce a population of highly-relativistic electrons with a maximum Lorentz factor above 10^7. These electrons scatter a small fraction of the microwave background photons in the present-day universe up to gamma-ray energies, thereby providing the gamma-ray background. The predicted diffuse flux agrees with the observed background over more than four decades in photon energy, and implies a mean cosmological density of baryons which is consistent with Big-Bang nucleosynthesis.Comment: 7 pages, 1 figure. Accepted for publication in Nature. (Press embargo until published.

Cosmic Ray Electrons in Groups and Clusters of Galaxies: Primary and Secondary Populations from a Numerical Cosmological Simulation

We study the generation and distribution of high energy electrons in cosmic environment and their observational consequences by carrying out the first cosmological simulation that includes directly cosmic ray (CR) particles. Starting from cosmological initial conditions we follow the evolution of primary and secondary electrons (CRE), CR ions (CRI) and a passive magnetic field. CRIs and primary CREs are injected and accelerated at large scale structure shocks. Secondary CREs are continuously generated through inelastic p-p collisions. We include spatial transport, adiabatic expansion/compression, Coulomb collisions, bremsstrahlung, synchrotron (SE)and inverse Compton (IC) emission. We find that, from the perspective of cosmic shock energy and acceleration efficiency, the few detections of hard X-ray radiation excess could be explained in the framework of IC emission of primary CREs in clusters undergoing high accretion/merger phase. Instead, IC emission from both primary and secondary CREs accounts at most for a small fraction of the radiation excesses detected in the extreme-UV (except for the Coma cluster as reported by Bowyer et al.1999). Next, we calculate the SE after normalizing the magnetic field so that for a Coma-like cluster ^1/2~3 \muG. Our results indicate that the SE from secondary CREs reproduces several general properties of radio halos, including the recently found P_1.4GHz vs T relation, the morphology and polarization of the emitting region and, to some extent, the spectral index. Moreover, SE from primary CREs turns out sufficient to power extended regions resembling radio relics observed at the outskirts of clusters. Again we find striking resemblance between morphology, polarization and spectral index of our synthetic maps and those reported in the literature.Comment: emulateapj, 27 pages, 10 figures, 5 tables; ApJ in pres

A distinctive requirement for p53 in the genome protective Topoisomerase 2a-dependent G2 arrest in hTERT positive cancer cells

Topoisomerase 2a (Topo2a)-dependent G2 arrest engenders faithful segregation of sister chromatids, yet in certain tumor cell lines where this arrest is dysfunctional, a PKCε-dependent failsafe pathway can be triggered. Here we elaborate on recent advances in understanding the underlying mechanisms associated with this G2 arrest by determining that p53-p21 signaling is essential for efficient arrest in cell lines, in patient-derived cells, and in colorectal cancer organoids. Regulation of this p53 axis required the SMC5/6 complex, which is distinct from the p53 pathways observed in the DNA damage response. Topo2a inhibition specifically during S phase did not trigger G2 arrest despite affecting completion of DNA replication. Moreover, in cancer cells reliant upon the alternative lengthening of telomeres (ALT) mechanism, a distinct form of Topo2a-dependent, p53-independent G2 arrest was found to be mediated by BLM and Chk1. Importantly, the previously described PKCε-dependent mitotic failsafe was engaged in hTERT-positive cells when Topo2a-dependent G2 arrest was dysfunctional and where p53 was absent, but not in cells dependent on the ALT mechanism. In PKCε knockout mice, p53 deletion elicited tumors were less aggressive than in PKCε-replete animals and exhibited a distinct pattern of chromosomal rearrangements. This evidence suggests the potential of exploiting synthetic lethality in arrest-defective hTERT-positive tumors through PKCε-directed therapeutic intervention.SignificanceThe identification of a requirement for p53 in stringent Topo2a-dependent G2 arrest and engagement of PKCε failsafe pathways in arrest-defective hTERT-positive cells provides a therapeutic opportunity to induce selective synthetic lethality