Drug-drug interactions in older patients with cancer: A report from the 15th Conference of the International Society of Geriatric Oncology, Prague, Czech Republic, November 2015

Drugs taken for cancer can interact with each other, with agents taken as part of supportive care, with drugs taken for comorbid conditions (which are particularly common in the elderly patients), and with herbal supplements and complementary medicines. We tend to focus on the narrow therapeutic window of cytotoxics, but the metabolism of tyrosine kinase inhibitors by the cytochrome P450 3A4 enzyme (CYP3A4) makes some TKIs particularly prone to interference with or from other agents sharing this pathway. There is also potential for adverse pharmacokinetic interactions with new hormonal agents used in advanced prostate cancer

Are Particles in Advection-Dominated Accretion Flows Thermal?

We investigate the form of the momentum distribution function for protons and electrons in an advection-dominated accretion flow (ADAF). We show that for all accretion rates, Coulomb collisions are too inefficient to thermalize the protons. The proton distribution function is therefore determined by the viscous heating mechanism, which is unknown. The electrons, however, can exchange energy quite efficiently through Coulomb collisions and the emission and absorption of synchrotron photons. We find that for accretion rates greater than \sim 10^{-3} of the Eddington accretion rate, the electrons have a thermal distribution throughout the accretion flow. For lower accretion rates, the electron distribution function is determined by the electron's source of heating, which is primarily adiabatic compression. Using the principle of adiabatic invariance, we show that an adiabatically compressed collisionless gas maintains a thermal distribution until the particle energies become relativistic. We derive a new, non-thermal, distribution function which arises for relativistic energies and provide analytic formulae for the synchrotron radiation from this distribution. Finally, we discuss its implications for the emission spectra from ADAFs.Comment: 29 pages (Latex), 3 Figures. Submitted to Ap

Going Around Again: Modelling Standing Ovations with a Flexible Agent-based Simulation Framework

We describe how we have used the CoSMoS process to trans- form a computer simulation originally developed for the simulation of plant development for use in modelling aspects of audience behaviour. An existing agent-based simulator is re-factored to simulate a completely dierent type of agent in 2D space. This is possible and desirable because the original simulator was designed with the intention that it could eas- ily be use to model a variety of dierent agents interacting in 2D and 3D space. The resulting simulation will be used to simulate the phe- nomena of standing ovations in audiences as a model system of tipping point behaviour. Continued development of this simulator, assisted by the CoSMoS process, has resulted in a general purpose lightweight sim- ulation framework

Spectrum of Optically Thin Advection Dominated Accretion Flow around a Black Hole: Application to Sgr A*

The global structure of optically thin advection dominated accretion flows which are composed of two-temperature plasma around black holes is calculated. We adopt the full set of basic equations including the advective energy transport in the energy equation for the electrons. The spectra emitted by the optically thin accretion flows are also investigated. The radiation mechanisms which are taken into accout are bremsstrahlung, synchrotron emission, and Comptonization. The calculation of the spectra and that of the structure of the accretion flows are made to be completely consistent by calculating the radiative cooling rate at each radius. As a result of the advection domination for the ions, the heat transport from the ions to the electrons becomes practically zero and the radiative cooling balances with the advective heating in the energy equation of the electrons. Following up on the successful work of Narayan et al. (1995), we applied our model to the spectrum of Sgr A*. We find that the spectrum of Sgr A* is explained by the optically thin advection dominated accretion flow around a black hole of the mass M_bh=10^6 M_sun. The parameter dependence of the spectrum and the structure of the accretion flows is also discussed.Comment: AAS LaTeX file; 26 pages; 12 ps figures; to be published in ApJ. PDF files are obtainable via following anonymous ftp. ftp://ftp.kusastro.kyoto-u.ac.jp/pub/manmoto/preprint/spec_sgrA.tar.g

Reaction–diffusion chemistry implementation of associative memory neural network

Unconventional computing paradigms are typically very difficult to program. By implementing efficient parallel control architectures such as artificial neural networks, we show that it is possible to program unconventional paradigms with relative ease. The work presented implements correlation matrix memories (a form of artificial neural network based on associative memory) in reaction–diffusion chemistry, and shows that implementations of such artificial neural networks can be trained and act in a similar way to conventional implementations

Hot Atmospheres Around Accreting Neutron Stars: A Possible Source For Hard X--ray Emission

The structure of static atmospheres around unmagnetized neutron stars undergoing steady, spherical accretion is discussed. We focus on the ``hot'' configurations presented by Turolla et al. (1994) and calculate the radiation spectrum using a characteristics method. In particular, it is found that e$^+$--e$^-$ pair production may affect significantly the external atmospheric layers, where positron and proton number densities become of the same order. The consequent increase of the scattering opacity lowers the Eddington limit and this, in turn, may drive a dynamical instability if the accretion luminosity is large enough, ultimately producing a rapid expulsion of the envelope. If ``hot'' states are indeed accessible, this mechanism could give rise to transient phenomena in hard X--rays of potential great astrophysical interest.Comment: 17 pages plus 3 postscript figures, to be published in Ap

Neutron-loaded outflows in gamma-ray bursts

Relativistic neutron-loaded outflows in gamma-ray bursts are studied at their early stages, before deceleration by a surrounding medium. The outflow has four components: radiation, electrons, protons and neutrons. The components interact with each other and exchange energy as the outflow expands. The presence of neutrons significantly changes the outflow evolution. Before neutrons decouple from protons, friction between the two components increases their temperatures by many orders of magnitude. After the decoupling, the gradual neutron decay inside the outflow has a drag effect on the protons and reduces their final Lorentz factor.Comment: 11 pages, 9 figures, submitted to MNRAS EMR current affiliation: JILA, UC at Boulde

Effect of varying the concentrations of carbohydrate and milk protein in rehydration solutions ingested after exercise in the heat

The present study investigated the relationship between the milk protein content of a rehydration solution and fluid balance after exercise-induced dehydration. On three occasions, eight healthy males were dehydrated to an identical degree of body mass loss (BML, approximately 1.8 %) by intermittent cycling in the heat, rehydrating with 150 % of their BML over 1 h with either a 60 g/l carbohydrate solution (C), a 40 g/l carbohydrate, 20 g/l milk protein solution (CP20) or a 20 g/l carbohydrate, 40 g/l milk protein solution (CP40). Urine samples were collected pre-exercise, post-exercise, post-rehydration and for a further 4 h. Subjects produced less urine after ingesting the CP20 or CP40 drink compared with the C drink (P<0.01), and at the end of the study, more of the CP20 (59 (SD 12) %) and CP40 (64 (SD 6) %) drinks had been retained compared with the C drink (46 (SD 9) %) (P,0.01). At the end of the study, whole-body net fluid balance was more negative for trial C (2470 (SD 154) ml) compared with both trials CP20 (2181 (SD 280) ml) and CP40 (2107 (SD 126) ml) (P<0.01). At 2 and 3 h after drink ingestion, urine osmolality was greater for trials CP20 and CP40 compared with trial C (P<0.05). The present study further demonstrates that after exercise-induced dehydration, a carbohydrate–milk protein solution is better retained than a carbohydrate solution. The results also suggest that high concentrations of milk protein are not more beneficial in terms of fluid retention than low concentrations of milk protein following exercise-induced dehydration

Intra-aortic balloon pump inserted through the subclavian artery: A minimally invasive approach to mechanical support in the ambulatory end-stage heart failure patient

ObjectiveIntra-aortic balloon pumps are traditionally inserted through the femoral artery, limiting the patient's mobility. We used alternate approaches of intra-aortic balloon pump insertion to provide temporary and minimally invasive support for patients with decompensating, end-stage heart failure. The present study describes the outcomes with closed-chest, transthoracic intra-aortic balloon pumps by way of the subclavian artery.MethodsDuring a 3-year period, 20 patients underwent subclavian artery–intra-aortic balloon pump in the setting of end-stage heart failure. The balloon was inserted through a polytetrafluoroethylene graft sutured to the right subclavian artery in 19 patients (95%) and to the left subclavian artery in 1 patient (5%). The goal of support was to bridge to transplantation in 17 patients (85%) and bridge to recovery in 3 patients (15%). The primary outcome measure was death during subclavian artery–intra-aortic balloon pump support. The secondary outcomes included survival to the intended endpoint of bridge to transplantation/bridge to recovery, complications during subclavian artery–intra-aortic balloon pump support (eg, stroke, limb ischemia, brachial plexus injury, dissection, bleeding requiring reoperation, and device-related infection), emergent surgery for worsening heart failure, and ambulation during intra-aortic balloon pump support.ResultsThe duration of balloon support ranged from 3 to 48 days (mean, 17.3 ± 13.1 days). No patients died during subclavian artery–intra-aortic balloon pump support. Of the 20 patients, 14 (70%) were successfully bridged to transplant or left ventricular-assist device. Two patients (10%) required emergent left ventricular-assist device for worsening heart failure.ConclusionsAn intra-aortic balloon pump inserted through the subclavian artery is a simple, minimally invasive approach to mechanical support and is associated with limited morbidity and facilitates ambulation in patients with end-stage heart failure

Three-dimensional Radiative Properties of Hot Accretion Flows onto the Galactic Centre Black Hole

By solving radiative transfer equations, we examine three-dimensional radiative properties of a magnetohydrodynamic accretion flow model confronting with the observed spectrum of Sgr A*, in the vicinity of supermassive black hole at the Galactic centre. As a result, we find that the core of radio emission is larger than the size of the event horizon shadow and its peak location is shifted from the gravitational centre. We also find that the self-absorbed synchrotron emissions by the superposition of thermal electrons within a few tens of the Schwartzschild radius can account for low-frequency spectra below the critical frequency $\nu_{c}\approx 10^{12}$ Hz. Above the critical frequency, the synchrotron self-Compton emission by thermal electrons can account for variable emissions in recent near-infrared observations. In contrast to the previous study by Ohsuga et al. (2005), we found that the X-ray spectra by Bremsstrahlung emission of thermal electrons for the different mass accretion rates can be consistent with both the flaring state and the quiescent state of Sgr A* observed by {\it Chandra}.Comment: 8 pages, 4 figures, submitted to MNRA