Scaling of decoherence effects in quantum computers

The scaling of decoherence rates with qubit number N is studied for a simple model of a quantum computer in the situation where N is large. The two state qubits are localized around well-separated positions via trapping potentials and vibrational centre of mass motion of the qubits occurs. Coherent one and two qubit gating processes are controlled by external classical fields and facilitated by a cavity mode ancilla. Decoherence due to qubit coupling to a bath of spontaneous modes, cavity decay modes and to the vibrational modes is treated. A non-Markovian treatment of the short time behaviour of the fidelity is presented, and expressions for the characteristic decoherence time scales obtained for the case where the qubit/cavity mode ancilla is in a pure state and the baths are in thermal states. Specific results are given for the case where the cavity mode is in the vacuum state and gating processes are absent and the qubits are in (a) the Hadamard state (b) the GHZ state.

Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart

Objective: This study investigated signaling pathways that may contribute to the potent positive inotropic effect of human urotensin-II (hU-II) in human isolated right atrial trabeculae obtained from patients with coronary artery disease. Methods: Trabeculae were set up in tissue baths and stimulated to contract at 1 Hz. Tissues were incubated with 20 nM hU-II with or without phorbol 12-myristate 13-acetate (PMA, 10 muM) to desensitize PKC, the PKC inhibitor chelerythrine (10 muM), 10 muM 4alpha-phorbol that does not desensitize PKC, the myosin light chain kinase inhibitor wortmannin (50 nM, 10 muM), or the Rho kinase inhibitor Y-27632 (0.1 - 10 muM). Activated RhoA was determined by affinity immunoprecipitation, and phosphorylation of signaling proteins was determined by SDS-PAGE. Results: hU-II caused a potent positive inotropic response in atrial trabeculae, and this was concomitant with increased phosphorylation of regulatory myosin light chain (MLC-2, 1.8 +/- 0.4-fold, P < 0.05, n = 6) and PKCalpha/betaII (1.4 +/- 0.2-fold compared to non-stimulated controls, P < 0.05, n = 7). Pretreatment of tissues with PMA caused a marked reduction in the inotropic effect of hU-II, but did not affect hU-II-mediated phosphorylation of MLC-2. The inotropic response was inhibited by chelerythrine, but not 4alpha-phorbol or wortmannin. Although Y-27632 also reduced the positive inotropic response to hU-II, this was associated with a marked reduction in basal force of contraction. RhoA. GTP was immunoprecipitated in tissues pretreated with or without hU-II, with findings showing no detectable activation of RhoA in the agonist stimulated tissues. Conclusions: The findings indicated that hU-II increased force of contraction in human heart via a PKC-dependent mechanism and increased phosphorylation of MLC-2, although this was independent of PKC. The positive inotropic effect was independent of myosin light chain kinase and RhoA-Rho kinase signaling pathways. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

NMR imaging of the diffusion of water at 310 K into semi-IPNs of PEM and Poly(HEMA-co-THFMA)

Magnetic resonance imaging has been used to monitor the diffusion of water at 310 K into a series of semi-IPNs of poly(ethyl methacrylate), PEM, and copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA. The diffusion was found to be well described by a Fickian kinetic model in the early stages of the water sorption process, and the diffusion coefficients were found to be slightly smaller than those for the copolymers of HEMA and THFMA, P(HEMA-co-THFMA), containing the same mole fraction of HEMA in the matrix. A second stage sorption process was identified in the later stage of water sorption by the PEM/PTHFMA semi-IPN and for the systems containing a P(HEMA-co-THFMA) component with a mole fraction HEMA of 0.6 or less. This was characterized by the presence of Water near the surface of the cylinders with a longer NMR T-2 relaxation time, which would be characteristic of mobile water, such as water present in large pores or surface fissures. The presence of the drug chlorhexidine in the polymer matrixes at a concentration of 5.625 wt % was found not to modify the properties significantly, but the diffusion coefficients for the water sorption were systematically smaller when the drug was present.

Treatment of partial-thickness burns: A prospective, randomized trial using Transcyte (TM)

Background: The purpose of the present study was to compare the effectiveness of three burns dressings (TransCyte, a bio-engineered skin substitute; Biobrane; and Silvazine cream (silver sulphadiazine and 0.2% chlorhexidine)), in treating children with partial-thickness burns. The primary objective was to determine the days until greater than or equal to90% re-epithelialization. The secondary objectives were to evaluate the number of wounds requiring autografting and the number of dressing changes/local wound care required. Methods: Study wounds were identified on each patient and the patients were randomized to receive TransCyte or Biobrane or Silvazine. Assessment of study wound closure began at 2 days after treatment and continued at least every other day thereafter until the wounds re-epithelialized or were autografted. A laser Doppler imaging system was used as an adjunct to assessing the depth of the burn. Results: Thirty-three patients with 58 wound sites enrolled in the study (TransCyte, n = 20, Biobrane, n = 17; Silvazine, n = 21). Mean time to re-epithelialization was 7.5 days for TransCyte, 9.5 days for Biobrane, and 11.2 days for Silvazine. The number of wounds requiring autografting were 5/21 (24%) for Silvazine, 3/17 (17%) for Biobrane, and 1/20 (5%) for TransCyte. Conclusions: When used in partial-thickness burns in children, TransCyte promotes fastest re-epithelialization and required less overall dressings then Biobrane or Silvazine. Patients who received Silvazine or Biobrane require more autografting than those treated with TransCyte.

Cytotoxicity of topical antimicrobial agents used in burn wounds in Australasia

Background: Burn sepsis is a leading cause of mortality and morbidity in patients with major burns. The use of topical antimicrobial agents has helped improve the survival of these patients. Silvazine (Sigma Pharmaceuticals, Melbourne, Australia) (1% silver sulphadiazine and 0.2% chlorhexidine digluconate) is used exclusively in Australasia, and there is no published study on its cytotoxicity. This study compared the relative cytotoxicity of Silvazine with 1% silver sulphadiazine (Flamazine (Smith & Nephew Healthcare. Hull. UK)) and a silver-based dressing (Acticoat (Smith & Nephew Healthcare, Hull, UK)). Methods: Dressings were applied to the centre of culture plates that were then seeded with keratinocytes at an estimated 25% confluence. The plates were incubated for 72 h and culture medium and dressings then removed. Toluidine blue was added to stain the remaining keratinocytes. Following removal of the dye, the plates were photographed under standard conditions and these digital images were analysed using image analysis software. Data was analysed using Student's t-test. Results: In the present study, Silvazine is the most cytotoxic agent. Seventy-two hour exposure to Silvazine in the present study results in almost no keratinocyte survival at all and a highly statistically significant reduction in cell survival relative to control, Acticoat and Flamazine (P

Misleading high tobramycin plasma concentrations can be caused by skin contamination of fingerprick blood following inhalation of nebulized tobramycin (TOBI (R)) - A short report

We observed unexpected high plasma concentrations of tobrarriycin (48.5 and 28.1 mg/L) in fingerprick blood samples after the nebulization of tobramycin solution for inhalation (tobramycin 300 mg/5 mL, TOBI(R)) by 2 young children aged 3 years. To investigate whether dermal contamination could be the source of error, 3 adult volunteers were present during another nebulization by a third child (age 2 years). The volunteers had exposure to tobramycin by handling the nebulizer or the nebule and also by inhalation from holding the child and being in close proximity while TOBI(R) was being administered. Five blood samples by fingerprick and 2 by venipuncture were collected and assayed for tobramycin concentration. On each occasion the site was swabbed with alcohol wipes to mimic standard patient sampling methods. One site was resampled after cleaning of hands with 2% chlorhexidine gluconate and water. Tobramycin concentrations from venipuncture 1-2 hours after nebulization were all < 0.2 mg/L except for 1 result of 1.2 mg/L. The tobramycin concentrations from fingerpricks before hand washing varied between 6.8 and 172 mg/L, and after hand washing between 0.3 and 17.6 mg/L. Contamination of fingers with tobramycin is likely to have caused the error in the 2 initial cases and did cause misleadingly elevated levels in the adult volunteers. We caution that therapeutic drug monitoring of nebulized tobramycin should not be done by fingerprick sampling, and care should be taken to avoid contamination of the venipuncture site.

A longitudinal controlled study of factors associated with mutans streptococci infection and caries lesion initiation in children 21 to 72 months old

Purpose: The purpose of this longitudinal study was to determine factors associated with mutans streptococci (MS) infection and development of caries lesions in a group of children 21 to 72 months old. Methods: The 63 caries-free children, recruited since birth, were divided into: (1) a study group of 24 children who were colonized with MS; and (2) a control group of 39 children without MS. The children were recalled every 3 months for approximately 24 months, and their social, medical, and dental histories were updated. At each recall, the teeth were checked for presence or absence of plaque, enamel hypoplasia, and caries lesions, and their MS status was assessed using a commercial test kit. Results: MS infection was associated with: (1) visible plaque (P < .01); (2) enamel hypoplasia (P < .05); (3) commencement of tooth-brushing after 12 months of age (P < .05); (4) lack of parental assistance with tooth-brushing (P < .025); and (5) increased hours of child care/school (P < .05). Four children (20%) were colonized at an age range of 21 to 36 months, 9 (45%) at 37 to 48 months, and 7 (35%) at 49 to 72 months (P < .001). Eight children who developed caries lesions: (1) had more hypoplastic teeth (P < .001); (2) ate sugar-containing snacks (P < .05); and (3) did not brush regularly with chlorhexidine gel (P < .01) compared to those who remained free of caries lesions. Conclusions: Lack of oral hygiene, consumption of sugar-containing snacks, and enamel hypoplasia are significant factors for both MS infection and caries lesion initiation.

The effects of equine skin preparation on transdermal drug penetration in vitro

An increasing number of formulations are applied to equine skin, yet variable penetration can affect efficacy, or the incidence of adverse effects, or both. To investigate the effects of common methods of skin preparation on transdermal drug penetration in vitro, we clipped, harvested, and froze skin samples from 5 Thoroughbred geldings. Thawed samples were prepared as follows: control (no preparation); cleaned with aqueous chlorhexidine (Aq-C, 0.1% w/v); cleaned with alcoholic chlorhexidine (Al-C, 0.5% w/v); shaved (Sh); or tape-stripped (Ta) with the use of adhesive tape. The samples were then placed in diffusion cells, and 2 g of methylsalicylate (MeSa) gel (Dencorub) was applied to the stratum corneum side. The penetration of MeSa and its analyte, salicylate (Sa), through the skin samples was measured over 10 h. Compared with control skin, significantly more MeSa penetrated through skin prepared with Al-C or Sh (P < 0.01) or with Aq-C or Ta (P < 0.05), and significantly more Sa was recovered in the receptor phase from skin prepared with Aq-C, Al-C, or Sh (P < 0.05) or with Ta (P < 0.01). A significantly higher rate of penetration and shorter lag time were also noted for MeSa with all the prepared skin samples, compared with the control samples. The results show that clinical techniques routinely used to clean or prepare skin can significantly affect the rate and extent of penetration of a topically applied drug. This may result in greater systemic availability of active drug, which could lead to enhanced efficacy and, possibly, a higher incidence of adverse effects.

Cyclodextrin complexes of antimicrobial agents

Poorly water-soluble drugs show an increase in solubility in the presence of cyclodextrins (CyD) due to the formation of a water-soluble complex between the drug and dissolved CyD. This study investigated the interactions of -Cyd and hydroxypropyl--CyD (HP--CyD, M.S. = 0.6) with antimicrobial agents of limited solubility in an attempt to increase their microbiological efficacy. The agents studied were chlorhexidine dihydrochloride (CHX), p-hydroxybenzoic acid esters (methyl, ethyl, proply and butyl) and triclosan. The interactions between the antimicrobials and CyDs were studied in solution and solid phases. Phase solubility studied revealed an enhancement in the aqueous drug solubility in the presence of the CyD and also gave an indication of the complex stability constant (Ks). The temperature-dependence of the stability constant of the complex was modelled by the van't Hoff plot which yielded the thermodynamic parameters for complexation. Further confirmation of the inclusion of the antimicrobials within the cavity of the CyDs in aqueous solution was obtained from proton magnetic resonance and ultraviolet absorption spectroscopies. The former method indicated that the chlorophenyl moiety of the CHX was included within the -CyD cavity and the stoichiometry of the complex formed was 1:1. The solid-phase complexes were prepared by freeze-drying. The inclusion complex of triclosan with HP--CyD was obtained from aqueous solution with the addition of ammonia. Evidence to confirm complex formation was obtained from DSC, IR and X-ray powder diffraction studies. Dissolution studies of the solid inclusion complexes using the dispersed powder technique illustrated their superior solubilities as compared to the equimolar physical mix of the guest and CyD. It was shown that these solutions of the complex were supersaturated with respect to the free guest. This was further demonstrated by diffusion studies which showed the flux of free drug from donor solutions of the antimicrobial-CyD complex to be significantly greater than the flux from donor suspensions of drug alone.

Chemical and physical methods of enhancing the percutaneous absorption of antimicrobial agents

Contrary to previously held beliefs, it is now known that bacteria exist not only on the surface of the skin but they are also distributed at varying depths beneath the skin surface. Hence, in order to sterilise the skin, antimicrobial agents are required to penetrate across the skin and eliminate the bacteria residing at all depths. Chlorhexidine is an antimicrobial agent with the widest use for skin sterilisation. However, due to its poor permeation rate across the skin, sterilisation of the skin cannot be achieved and, therefore, the remaining bacteria can act as a source of infection during an operation or insertion of catheters. The underlying theme of this study is to enhance the permeation of this antimicrobial agent in the skin by employing chemical (enhancers and supersaturated systems) or physical (iontophoresis) techniques. The hydrochloride salt of chlorhexidine (CHX), a poorly soluble salt, was used throughout this study. The effect of ionisation on in vitro permeation rate across the excised human epidennis was investigated using Franz-type diffusion cells. Saturated solutions of CHX were used as donor and the variable studied was vehicle pH. Permeation rate was increased with increasing vehicle pH. The pH effect was not related to the level of ionisation of the drug. The effect of donor vehicle was also studied using saturated solutions of CHX in 10% and 20% ethanol as the donor solutions. Permeation of CHX was enhanced by increasing the concentration of ethanol which could be due to the higher concentration of CHX in the donor phase and the effect of ethanol itself on the membrane. The interplay between drug diffusion and enhancer pretreatment of the epidennis was studied. Pretreatment of the membrane with 10% Azone/PG demonstrated the highest diffusion rate followed by 10% olcic acid/PG pretreatment compared to other pretreatment regimens (ethanol, dimethyl sulfoxide (DMSO), propylene glycol (PG), sodium dodecyl sulphate (SDS) and dodecyl trimethyl ammonium bromide (DT AB). Differential Scanning Calorimetry (DSC) was also employed to study the mode of action of these enhancers. The potential of supersaturated solutions in enhancing percutaneous absorption of CHX was investigated. Various anti-nucleating polymers were screened in order to establish the most effective agent. Polyvinylpyrrolidone (PVP, K30) was found to be a better candidate than its lower molecular weight counterpart (K25) and hydroxypropyl methyleellulose (HPMC). The permeation studies showed an increase in diffusion rate by increasing the degree of saturation. Iontophoresis is a physical means of transdemal drug delivery enhancement that causes an increased penetration of molecules into or through the skin by the application of an electric field. This technique was employed in conjunction with chemical enhancers to assess the effect on CHX permeation across the human epidermis. An improved transport of CHX, which was pH dependant was observed upon application of the current. Combined use of iontophoresis and chemical enhancers further increased the CHX transport indicating a synergistic effect. Pretreatment of the membrane with 10% Azone/PG demonstrated the greatest effect.

A systematic review of treatments for atopic dermatitis

Atopic dermatitis is a very common inflammatory skin disease, particularly in children. A systematic review of randomised controlled trials of treatments for atopic dermatitis (AD) was carried out to assess how many trials exist, what they cover, what they do not cover, the research gaps, provide a 'blue print' for future Cochrane Reviews and assist those making treatment recommendations by summarising the available RCT evidence, using descriptive statistics. The Cochrane Collaboration systematic review process formed the basis of the methodology, from which over 4000 studies were located via electronic database searches and hand searching of journals. A total of 292 trials were finally included covering 9 treatment groups and over 48 individual treatments. There are lots of trials covering lots of interventions but gaps are evident. However, there is evidence of a benefit in the treatment of atopic dermatitis with topical corticosteroids, psychological approaches, UV light, ascomycin derivatives, topical tacrolimus and oral cyclosporin. Treatments that show limited evidence of a benefit include non-sedatory antihistamines, topical doxepin, the oral antibiotic Cefadroxil on clinically infected AD, the topical antibacterial Mupirocin on clinically uninfected AD, Chinese herbs, hypnotherapy and biofeedback, massage therapy, dietary manipulation, house dust mite reduction, patient education, emollients, allergen antibody complexes of house dust mite and thymic extracts. Treatments that show no evidence of benefit include sedatory antihistamines, oral sodium cromoglycate, oral antibiotics on clinically uninfected AD, topical antibacterials, topical antifungals, aromatherapy essential oils, borage oil, fish oil, evening primrose oil, enzyme-free clothes detergent, cotton clothing, house dust mite hyposensitisation, salt baths, topical coal tar, topical cyclosporin and platelet-activating-factor antagonist. When interpreting the conclusions of this thesis it is important to understand that lack of evidence does not equal lack of efficacy, particularly considering the interventions that are commonly in use today to treat atopic dermatitis that have not been subjected to RCTs, such as occlusive dressings, water softening devices and stress management among many others.

Antibiotic and biocide resistance in Salmonella enterica and Escherichia coli 0157

Bacterial resistance to antibiotics and biocides is a prevalent problem, which may be exacerbated by the commonplace and often unnecessary inclusion of biocides into domestic products. Addition of antimicrobials, to domestic disinfectants has raised concern about promoting microbial resistance and potential cross-resistance to therapeutic antibiotics. This study investigated the potential for resistance in Salmonella enterica serovars Enteritidis, Typhimurium, Virchow and Escherichia call 0157 to commonly used biocides, to identify mechanisms underlying resistance and whether these provided cross-resistance to antibiotics. Salmonella enterica and E. coli 0157 strains were serially exposed to sub-inhibitory. concentrations of erythromycin (ERY), benzalkonium chloride (BKC), chlorhexidine hydrochloride (CHX)and triclosan (TLN). Once resistance was achieved permeability changes in the outer membrane, including LPS, cell surface charge and hydrophobicityand the presence of,an active efflux were investigated as possible resistance candidates. Thin layer chromatography (TLC) and Gas chromatography (GC) were carried out to examine fatty acid and lipid changes in E. coli 0157 isolates with reduced susceptibility to TLN. Cross-resistance was studied by the Stoke's method and standard microdilution assays. Examination of the outer membrane proteins and LPS did not reveal any significant changes between parent and resistant strains. The hydrophobicity of the cells increased as the cells were passaged and became less. susceptible. An active efflux system was the most likely mechanism of resistance in all strains tested and a fab1 mutation was associated with E. coli 0157 resistant to TLN isolates. In all isolates investigated the resistance was stable for over 30 passages in biocide-free media. A high degree of cross-resistance was obtained in TLN-resjstant Escherichia coli 0157 strains, which repeatedly exerted decreased susceptibility to various antimicrobials, including chloramphenicol, erythromycin, imipenem, tetracycline and trimethoprirn:, as well as to various biocides. The results of this laboratory-based investigation suggest that it is possible for microorganisms to become resistant to biocides when repeatedly exposed to sublethal concentrations. This may be especially the case in the domestic environment where administration of biocides is poorly controlled. Eventually it could lead to the undesirable situation of resident strains becoming resistant to disinfection and cross resistant to other antimicrobials.

Mechanisms of chromium deposition and dissolution under direct and pulse reverse plating conditions

Baths containing sulphuric acid as catalyst and others with selected secondary catalysts (methane sulphonic acid - MSA, SeO2, a KBrO3/KIO3 mixture, indium, uranium and commercial high speed catalysts (HEEF-25 and HEEF-405)) were studied. The secondary catalysts influenced CCE, brightness and cracking. Chromium deposition mechanisms were studied in Part II using potentiostatic and potentiodynamic electroanalytical techniques under stationary and hydrodynamic conditions. Sulphuric acid as a primary catalyst and MSA, HEEF-25, HEEF-405 and sulphosalycilic acid as co-catalysts were explored for different rotation, speeds and scan rates. Maximum current was resolved into diffusion and kinetically limited components, and a contribution towards understanding the electrochemical mechanism is proposed. Reaction kinetics were further studied for H2SO4, MSA and methane disulphonic acid catalysed systems and their influence on reaction mechanisms elaborated. Charge transfer coefficient and electrochemical reaction rate orders for the first stage of the electrodeposition process were determined. A contribution was made toward understanding of H2SO4 and MSA influence on the evolution rate of hydrogen. Anodic dissolution of chromium in the chromic acid solution was studied with a number of techniques. An electrochemical dissolution mechanism is proposed, based on the results of rotating gold ring disc experiments and scanning electron microscopy. Finally, significant increases in chromium electrodeposition rates under non-stationary conditions (PRC mode) were studied and a deposition mechanisms is elaborated based on experimental data and theoretical considerations.