Sequential effects of propofol on functional brain activation induced by auditory language processing: an event‐related functional magnetic resonance imaging study

Background. We have investigated the effect of propofol on language processing using event‐related functional magnetic resonance imaging (MRI). Methods. Twelve healthy male volunteers underwent MRI scanning at a magnetic field strength of 3 Tesla while performing an auditory language processing task. Functional images were acquired from the perisylvian cortical regions that are associated with auditory and language processing. The experiment consisted of three blocks: awake state (block 1), induction of anaesthesia with 3 mg kg-1 propofol (block 2), and maintenance of anaesthesia with 3 mg kg-1 h-1 propofol (block 3). During each block normal sentences and pseudo‐word sentences were presented in random order. The subjects were instructed to press a button to indicate whether a sentence was made up of pseudo‐words or not. All subjects stopped responding during block two. The data collected before and after the subjects stopped responding during this block were analyzed separately. In addition, propofol plasma concentrations were measured and the effect‐site concentrations of propofol were calculated. Results. During wakefulness, language processing induced brain activation in a widely distributed temporofrontal network. Immediately after unresponsiveness, activation disappeared in frontal areas but persisted in both temporal lobes (block 2 second half, propofol effect‐site concentration: 1.51 µg ml-1). No activation differences related to the task were observed during block 3 (propofol effect‐site concentration: 4.35 µg ml-1). Conclusion. Our findings suggest sequential effects of propofol on auditory language processing networks. Brain activation firstly declines in the frontal lobe before it disappears in the temporal lobe. Br J Anaesth 2004; 92: 641-5

Experimental and computational characterization of a modified GEC cell for dusty plasma experiments

A self-consistent fluid model developed for simulations of micro- gravity dusty plasma experiments has for the first time been used to model asymmetric dusty plasma experiments in a modified GEC reference cell with gravity. The numerical results are directly compared with experimental data and the experimentally determined dependence of global discharge parameters on the applied driving potential and neutral gas pressure is found to be well matched by the model. The local profiles important for dust particle transport are studied and compared with experimentally determined profiles. The radial forces in the midplane are presented for the different discharge settings. The differences between the results obtained in the modified GEC cell and the results first reported for the original GEC reference cell are pointed out

Collisional kinetics of non-uniform electric field, low-pressure, direct-current discharges in H2_{2}

A model of the collisional kinetics of energetic hydrogen atoms, molecules, and ions in pure H$_2$ discharges is used to predict H$_\alpha$ emission profiles and spatial distributions of emission from the cathode regions of low-pressure, weakly-ionized discharges for comparison with a wide variety of experiments. Positive and negative ion energy distributions are also predicted. The model developed for spatially uniform electric fields and current densities less than $10^{-3}$ A/m$^2$ is extended to non-uniform electric fields, current densities of $10^{3}$ A/m$^2$, and electric field to gas density ratios $E/N = 1.3$ MTd at 0.002 to 5 Torr pressure. (1 Td = $10^{-21}$ V m$^2$ and 1 Torr = 133 Pa) The observed far-wing Doppler broadening and spatial distribution of the H$_\alpha$ emission is consistent with reactions among H$^+$, H$_2^+$, H$_3^+$, and H$^-H$ ions, fast H atoms, and fast H$_2$ molecules, and with reflection, excitation, and attachment to fast H atoms at surfaces. The H$_\alpha$ excitation and H$^-$ formation occur principally by collisions of fast H, fast H$_2$, and H$^+$ with H$_2$. Simplifications include using a one-dimensional geometry, a multi-beam transport model, and the average cathode-fall electric field. The H$_\alpha$ emission is linear with current density over eight orders of magnitude. The calculated ion energy distributions agree satisfactorily with experiment for H$_2^+$ and H$_3^+$, but are only in qualitative agreement for H$^+$ and H$^-$. The experiments successfully modeled range from short-gap, parallel-plane glow discharges to beam-like, electrostatic-confinement discharges.Comment: Submitted to Plasmas Sources Science and Technology 8/18/201

The Gaseous Electronics Conference radio‐frequency reference cell: A defined parallel‐plate radio‐frequency system for experimental and theoretical studies of plasma‐processing discharges

A ‘‘reference cell’’ for generating radio‐frequency (rf) glow discharges in gases at a frequency of 13.56 MHz is described. The reference cell provides an experimental platform for comparing plasma measurements carried out in a common reactor geometry by different experimental groups, thereby enhancing the transfer of knowledge and insight gained in rf discharge studies. The results of performing ostensibly identical measurements on six of these cells in five different laboratories are analyzed and discussed. Measurements were made of plasma voltage and current characteristics for discharges in pure argon at specified values of applied voltages, gas pressures, and gas flow rates. Data are presented on relevant electrical quantities derived from Fourier analysis of the voltage and current wave forms. Amplitudes, phase shifts, self‐bias voltages, and power dissipation were measured. Each of the cells was characterized in terms of its measured internal reactive components. Comparing results from different cells provides an indication of the degree of precision needed to define the electrical configuration and operating parameters in order to achieve identical performance at various laboratories. The results show, for example, that the external circuit, including the reactive components of the rf power source, can significantly influence the discharge. Results obtained in reference cells with identical rf power sources demonstrate that considerable progress has been made in developing a phenomenological understanding of the conditions needed to obtain reproducible discharge conditions in independent reference cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70394/2/RSINAK-65-1-140-1.pd

Hepatocellular Carcinoma Recurrence and Death Following Living and Deceased Donor Liver Transplantation

We examined mortality and recurrence of hepatocellular carcinoma (HCC) among 106 transplant candidates with cirrhosis and HCC who had a potential living donor evaluated between January 1998 and February 2003 at the nine centers participating in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Cox regression models were fitted to compare time from donor evaluation and time from transplant to death or HCC recurrence between 58 living donor liver transplant (LDLT) and 34 deceased donor liver transplant (DDLT) recipients. Mean age and calculated Model for End-Stage Liver Disease (MELD) scores at transplant were similar between LDLT and DDLT recipients (age: 55 vs. 52 years, p = 0.21; MELD: 13 vs. 15, p = 0.08). Relative to DDLT recipients, LDLT recipients had a shorter time from listing to transplant (mean 160 vs. 469 days, p < 0.0001) and a higher rate of HCC re currence within 3 years than DDLT recipients (29% vs. 0%, p = 0.002), but there was no difference in mortality or the combined outcome of mortality or recurrence. LDLT recipients had lower relative mortality risk than patients who did not undergo LDLT after the center had more experience (p = 0.03). Enthusiasm for LDLT as HCC treatment is dampened by higher HCC recurrence compared to DDLT

Consequences of Cold-Ischemia Time on Primary Nonfunction and Patient and Graft Survival in Liver Transplantation: A Meta-Analysis

Introduction: The ability to preserve organs prior to transplant is essential to the organ allocation process. Objective: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT) and primary nonfunction (PNF), patient and graft survival in liver transplant. Methods: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. Results: Twenty-six studies met criteria. Functionally, PNF%=-6.678281+0.9134701*CIT Mean+0.1250879*(CIT Mean-9.89535) 2 - 0.0067663*(CIT Mean-9.89535) 3, r2=.625, p<.0001. Mean patient survival: 93 % (1 month), 88 % (3 months), 83 % (6 months) and 83 % (12 months). Mean graft survival: 85.9 % (1 month), 80.5 % (3 months), 78.1 % (6 months) and 76.8 % (12 months). Maximum patient and graft survival occurred with CITs between 7.5-12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. Conclusion: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ. © 2008 Stahl et al

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study)

Background Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. Methods A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. Results Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 (<US$16) and not cost-effective. Conclusions Adherence with travoprost was high and not further increased by the intervention. Nevertheless, the study demonstrated that provision of information, tailored to the individual, was inexpensive and able to achieve high patient satisfaction with respect to information about glaucoma medication. Measurement of adherence remains problematic since awareness of study participation may cause a change in participant behaviour

Synergistic Reversal of Intrahepatic HCV-Specific CD8 T Cell Exhaustion by Combined PD-1/CTLA-4 Blockade

Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is preferentially upregulated in PD-1+ T cells from the liver but not blood of chronically HCV-infected patients. PD-1/CTLA-4 co-expression in intrahepatic T cells was associated with a profound HCV-specific effector dysfunction that was synergistically reversed by combined PD-1/CTLA-4 blockade in vitro, but not by blocking PD-1 or CTLA-4 alone. A similar effect was observed in circulating HCV-specific CD8 T cells with increased PD-1/CTLA-4 co-expression during acute hepatitis C. The functional response to combined blockade was directly associated with CTLA-4 expression, lost with CD28-depletion and CD4-independent (including CD4+FoxP3+ Tregs). We conclude that PD-1 and CTLA-4 pathways both contribute to virus-specific T cell exhaustion at the site of viral replication by a redundant mechanism that requires combined PD-1/CTLA-4 blockade to reverse. These findings provide new insights into the mechanisms of virus-specific T cell dysfunction, and suggest that the synergistic effect by combined inhibitory receptor blockade might have a therapeutic application against chronic viral infection in vivo, provided that it does not induce autoimmunity