Effects of pre- or postoperative morphine and of preoperative ketamine in experimental surgery in rats, evaluated by pain scoring and c-fos expression

Since Wall (1988) hypothesised a beneficial post surgical effect of preoperative analgesic treatment (so-called pre-emptive analgesic treatment) as a supplement to postoperative analgesic treatment, the concept has been subject to many scientific debates. According to the hypothesis, applying analgesics before the nociceptive stimulus is beneficial due to reduced wind-up and reduced central sensitisation resulting in diminished risk of postoperative hyperalgesia and allodynia (Woolf and Chong, 1993). The scientific literature provides conflicting evidence for this theory. Beneficial effect of preemptive analgesic treatment has been reported after pre-emptive treatment with local analgesics, opioids and NSAID´s compared with placebo (Woolf and Chong, 1993). Some clinical settings have showed beneficial analgesic effect of preemptive analgesia, when the same pre-emptive and postoperative treatments with lidocaine (Ejlersen et al., 1992; Doyle and Bowler, 1998) or opioids (Katz et al., 1992) were compared. However, Dahl et al. (1992) and Elhakim et al. (1995) did not obtained supportive results in their clinical studies.In the majority of studies using animal models addressing this concept, the nociceptive stimulus has been obtained by injection of irritating chemicals, in particular formalin. When somatic tissue is damaged or irritated, nociceptive receptors are activated by peripheral release of extracellular inflammatory mediators. The activated receptors lead the signal to the synapses in the dorsal horn of the spinal cord as a 2-phased signal. In the acute first phase, nociceptive stimuli are mediated centrally through Aä fibres fibres. During the slower and long-lasting second phase, the nociceptive stimuli are mediated mainly through C-fibres (Cross et al., 1994). The release of extracellular inflammatory mediators increases the peripheral excitability, which leads to hyperalgesia (Woolf, 1995). Repetitive peripheral nociceptive impulses mediated through C-fibres result in an increased central excitability of dorsal appears to be in part mediated through N-methylhorn neurones. This state is called wind-up and appears to be in part mediated through N-methyl- D-aspartate (NMDA) receptors on dorsal horn secondary nociceptive neurones. Transmission of multiple slow stimuli leads to release of glutamate, which removes the Mg++-block in the NMDA receptor and allows substantial Ca++-inflow (Urban et al., 1994). NMDA receptor antagonists bind to the same site as Mg++ and prevents Ca++- inflow (Hirota and Lambert, 1996; Kress, 1997). NMDA-receptor antagonists can prevent wind-up but not the initial responses of the neurones, whereas the reverse is true for opioids (Chapman and Dickenson, 1992). NMDA-antagonists have no effect on pain of the acute first phase, but may act synergistic to the analgesic effect of opioids (Chapman and Dickenson, 1992; Honoré et al., 1996). Only few studies deal with a postoperative experimental model in animals and those available are conflicting. Brennan et al. (1996) developed an elegant postoperative model in rats with surgical intervention on the plantar surface of the hind foot. In this study a relationship was found between behavioural pain observation scores and mechanical hyperalgesia. Ovariohysterectomized rats have also been used as animal models of postoperative pain (Lascelles et al. 1995). A commonly used method of determining the nociceptive activity caused by a peripheral stimulus is to identify and quantify the nuclear protein Fos expressed in secondary nociceptive neurones in the spinal cord. c-fos is an immediate early gene (IEG), that encodes for Fos. IEG’s are rapidly and transiently induced in neuronal cells within minutes of extracellular stimulation (Sheng and Greenberg, 1990). The c-fos mRNA accumulates, and reaches its peak after 30 to 40 minutes. The Fos level peaks approximately two hours after induction of c-fos (Harris, 1998). Since Hunt (1987) reported, that peripheral inflammation induced c-fos in neurones in the dorsal horn of the spinal cord, many studies have shown the relationship between nociception and cfos expression.The aim of the present investigation was to study the effect of pre-emptive versus postoperative opioid analgesic treatment by use of the surgical model of Brennan et al. (1996) and combine the pre-emptive and postoperative opioid treatment with pre-emptive ketamine. The effects were quantified by stereological estimation of the number of dorsal horn neurones expressing c-fos and pain scoring from the operated hind foot

Foreground removal from WMAP 7yr polarization maps using an MLP neural network

One of the fundamental problems in extracting the cosmic microwave background signal (CMB) from millimeter/submillimeter observations is the pollution by emission from the Milky Way: synchrotron, free-free, and thermal dust emission. To extract the fundamental cosmological parameters from CMB signal, it is mandatory to minimize this pollution since it will create systematic errors in the CMB power spectra. In previous investigations, it has been demonstrated that the neural network method provide high quality CMB maps from temperature data. Here the analysis is extended to polarization maps. As a concrete example, the WMAP 7-year polarization data, the most reliable determination of the polarization properties of the CMB, has been analysed. The analysis has adopted the frequency maps, noise models, window functions and the foreground models as provided by the WMAP Team, and no auxiliary data is included. Within this framework it is demonstrated that the network can extract the CMB polarization signal with no sign of pollution by the polarized foregrounds. The errors in the derived polarization power spectra are improved compared to the errors derived by the WMAP Team.Comment: Accepted for publication in Astrophysics & Space Scienc

Growth suppression by transforming growth factor beta 1 of human small-cell lung cancer cell lines is associated with expression of the type II receptor.

Nine human small-cell lung cancer cell lines were treated with transforming growth factor beta 1 (TGF-beta 1). Seven of the cell lines expressed receptors for transforming growth factor beta (TGF-beta-r) in different combinations between the three human subtypes I, II and III, and two were receptor negative. Growth suppression was induced by TGF-beta 1 exclusively in the five cell lines expressing the type II receptor. For the first time growth suppression by TGF-beta 1 of a cell line expressing the type II receptor without coexpression of the type I receptor is reported. No effect on growth was observed in two cell lines expressing only type III receptor and in TGF-beta-r negative cell lines. In two cell lines expressing all three receptor types, growth suppression was accompanied by morphological changes. To evaluate the possible involvement of the retinoblastoma protein (pRb) in mediating the growth-suppressive effect of TGF-beta 1, the expression of functional pRb, as characterised by nuclear localisation, was examined by immunocytochemistry. Nuclear association of pRb was only seen in two of the five TGF-beta 1-responsive cell lines. These results indicate that in SCLC pRb is not required for mediation of TGF-beta 1-induced growth suppression

Recovering the properties of high redshift galaxies with different JWST broad-band filters

Imaging with the James Webb Space Telescope (JWST) will allow for observing the bulk of distant galaxies at the epoch of reionisation. The recovery of their properties, such as age, color excess E(B-V), specific star formation rate (sSFR) and stellar mass, will mostly rely on spectral energy distribution fitting, based on the data provided by JWST's two imager cameras, namely the Near Infrared Camera (NIRCam) and the Mid Infrared Imager (MIRI). In this work we analyze the effect of choosing different combinations of NIRCam and MIRI broad-band filters, from 0.6 {\mu}m to 7.7 {\mu}m, on the recovery of these galaxy properties. We performed our tests on a sample of 1542 simulated galaxies, with known input properties, at z=7-10. We found that, with only 8 NIRCam broad-bands, we can recover the galaxy age within 0.1 Gyr and the color excess within 0.06 mag for 70% of the galaxies. Besides, the stellar masses and sSFR are recovered within 0.2 and 0.3 dex, respectively, at z=7-9. Instead, at z=10, no NIRCam band traces purely the {\lambda}> 4000 {\AA} regime and the percentage of outliers in stellar mass (sSFR) increases by > 20% (> 90%), in comparison to z=9. The MIRI F560W and F770W bands are crucial to improve the stellar mass and the sSFR estimation at z=10. When nebular emission lines are present, deriving correct galaxy properties is challenging, at any redshift and with any band combination. In particular, the stellar mass is systematically overestimated in up to 0.3 dex on average with NIRCam data alone and including MIRI observations improves only marginally the estimation.Comment: 21 pages, 11 figures, 4 tables. Accepted for publication at the ApJ

Neural Modeling and Control of Diesel Engine with Pollution Constraints

The paper describes a neural approach for modelling and control of a turbocharged Diesel engine. A neural model, whose structure is mainly based on some physical equations describing the engine behaviour, is built for the rotation speed and the exhaust gas opacity. The model is composed of three interconnected neural submodels, each of them constituting a nonlinear multi-input single-output error model. The structural identification and the parameter estimation from data gathered on a real engine are described. The neural direct model is then used to determine a neural controller of the engine, in a specialized training scheme minimising a multivariable criterion. Simulations show the effect of the pollution constraint weighting on a trajectory tracking of the engine speed. Neural networks, which are flexible and parsimonious nonlinear black-box models, with universal approximation capabilities, can accurately describe or control complex nonlinear systems, with little a priori theoretical knowledge. The presented work extends optimal neuro-control to the multivariable case and shows the flexibility of neural optimisers. Considering the preliminary results, it appears that neural networks can be used as embedded models for engine control, to satisfy the more and more restricting pollutant emission legislation. Particularly, they are able to model nonlinear dynamics and outperform during transients the control schemes based on static mappings.Comment: 15 page

Phonon-induced quadrupolar ordering of the magnetic superconductor TmNi2_2B2_2C

We present synchrotron x-ray diffraction studies revealing that the lattice of thulium borocarbide is distorted below T_Q = 13.5 K at zero field. T_Q increases and the amplitude of the displacements is drastically enhanced, by a factor of 10 at 60 kOe, when a magnetic field is applied along [100]. The distortion occurs at the same wave vector as the antiferromagnetic ordering induced by the a-axis field. A model is presented that accounts for the properties of the quadrupolar phase and explains the peculiar behavior of the antiferromagnetic ordering previously observed in this compound.Comment: submitted to PR

Mean-field model of the ferromagnetic ordering in the superconducting phase of ErNi_2B_2C

A mean-field model explaining most of the details in the magnetic phase diagram of ErNi_2B_2C is presented. The low-temperature magnetic properties are found to be dominated by the appearance of long-period commensurate structures. The stable structure at low temperatures and zero field is found to have a period of 40 layers along the a direction, and upon cooling it undergoes a first-order transition at T_C = 2.3 K to a different 40-layered structure having a net ferromagnetic component of about 0.4 mu_B/Er. The neutron-diffraction patterns predicted by the two 40-layered structures, above and below T_C, are in agreement with the observations of Choi et al.Comment: 4 pages, 3 figures (Revtex4

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence