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Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); Grant(s): 338944-GOCAT, Carbene-metal-amides are soluble and thermally stable materials which have recently emerged as emitters in high-performance organic light-emitting diodes. Here we synthesise carbene-metal-amide photoemitters with CF3-substituted ligands to show sky-blue to deep-blue photoluminescence from charge-transfer excited states. We demonstrate that the emission colour can be adjusted from blue to yellow and observe that the relative energies of charge transfer and locally excited triplet states influence the performance of the deep-blue emission. High thermal stability and insensitivity to aggregation-induced luminescence quenching allow us to fabricate organic light-emitting diodes in both host-free and host-guest architectures. We report blue devices with a peak external quantum efficiency of 17.3% in a host-free emitting layer and 20.9% in a polar host. Our findings inform the molecular design of the next generation of stable blue carbene-metal-amide emitters.

Organic emitters exhibiting delayed fluorescence (DF) are promising luminescent materials for next-generation organic light-emitting diodes (OLEDs). Faster intersystem crossing rates and shorter em...

There is a growing body of experimental work showing that protein aggregates associated with amyloid fibrils feature intrinsic fluorescence. In order to understand the microscopic origin of this behavior observed in non-aromatic aggregates of peptides and proteins, we conducted a combined experimental and computational study on the optical properties of amyloid-derived oligopeptides in the near-UV region. We have focused on a few model systems having charged termini (zwitterionic) or acetylated termini. For the zwitterionic system, we were able to simulate the longer tail absorption in the near UV (250-350 nm), supporting the experimental results in terms of excitation spectra. We analyzed the optical excitations responsible for the low-energy absorption and found a large role played by charge-transfer states around the termini. These charge-transfer excitations are very sensitive to the conformation of the peptide and in realistic fibrils may involve inter and intra chain charge reorganization.

Significance Intrinsic fluorescence of nonaromatic amino acids is a puzzling phenomenon with an enormous potential in biophotonic applications. The physical origins of this effect, however, remain elusive. Herein, we demonstrate how specific hydrogen bond networks can modulate fluorescence. We highlight the key role played by short hydrogen bonds, present in the protein structure, on the ensuing fluorescence. We provide detailed experimental and molecular evidence to explain these unusual nonaromatic optical properties. Our findings should benefit the design of novel optically active biomaterials for applications in biosensing and imaging., Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications.

It has been previously found that through an established synthesis of the macrocycle boron subnaphthalocyanine (BsubNc) that random bay-position chlorination occurs and results in a mixed alloyed composition that cannot be separated; called chloro-(chloron)-boron subnaphthalocyanines (Cl-ClnBsubNcs). Through modifications of the synthetic method, amounts of the average bay-position chlorination can be varied. Cl-ClnBsubNcs are fluorescent and therefore here we explore the effect of the amount of bay-position chlorination on the photoluminescent and electroluminescent properties of Cl-ClnBsubNcs. Distinct from previous reports detailing the positive impact of higher average bay-position chlorination, we find that the photophysical processes important to OLEDs improve with lower average bay-position chlorination. A higher degree of bay-position chlorine shows higher nonradiative recombination rates, lower photoluminescence quantum efficiencies and a basic OLEDs exhibits a greater host emission fraction, implying less effective energy transfer. These results advance the consideration of subnaphthalocyanines for light-emitting and optoelectronic applications.

Carbene-metal-amides (CMAs) are a promising family of donor–bridge–acceptor molecular charge-transfer (CT) emitters for organic light-emitting diodes. A universal approach is demonstrated to tune the energy of their CT emission. A blueshift of up to 210 meV is achievable in solid state via dilution in a polar host matrix. The origin of this shift has two components: constraint of thermally-activated triplet diffusion, and electrostatic interactions between guest and polar host. This allows the emission of mid-green CMA archetypes to be tuned to sky blue without chemical modifications. Monte-Carlo simulations based on a Marcus-type transfer integral successfully reproduce the concentration- and temperature-dependent triplet diffusion process, revealing a substantial shift in the ensemble density of states in polar hosts. In gold-bridged CMAs, this shift does not lead to a significant change in luminescence lifetime, thermal activation energy, reorganization energy, or intersystem crossing rate. These discoveries offer new insight into coupling between the singlet and triplet manifolds in CMA materials, revealing a dominant interaction between states of CT character. The same approach is employed using materials which have been chemically modified to alter the energy of their CT state directly, shifting the emission of sky-blue chromophores into the practical blue range.

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, we show that specific hydrogen bonding networks can significantly affect fluorescence employing a combined experimental and computational approach. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared to L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease non-radiative transition probabilities. Our findings open the doors for the design of new photoactive materials with biophotonic applications.Significance statementIntrinsic fluorescence of non-aromatic amino acids is a puzzling phenomenon with an enormous potential for technological and biomedical applications. The physical origins of this effect, however, remain elusive. Herein, we demonstrate how specific hydrogen bond networks can modulate fluorescence. We highlight the key role played by short hydrogen bonds in the networks on the ensuing fluorescence and we provide a detailed molecular mechanism to explain this unusual non-aromatic optical properties. Our findings should benefit the design of novel optically active biomaterials for applications in biosensing and imaging.

Multiple donor-acceptor-type carbazole-benzonitrile derivatives that exhibit thermally activated delayed fluorescence (TADF) are the state of the art in efficiency and stability in sky-blue organic light-emitting diodes. However, such a motif still suffers from low reverse intersystem crossing rates (kRISC ) with emission peaks 60 h at an initial luminance of 1000 cd m-2 .

Charge-transfer (CT) complexes, formed by electron transfer from a donor to an acceptor, play a crucial role in organic semiconductors. Excited-state CT complexes, termed exciplexes, harness both singlet and triplet excitons for light emission, and are thus useful for organic light-emitting diodes (OLEDs). However, present exciplex emitters often suffer from low photoluminescence quantum efficiencies (PLQEs), due to limited control over the relative orientation, electronic coupling and non-radiative recombination channels of the donor and acceptor subunits. Here, we use a rigid linker to control the spacing and relative orientation of the donor and acceptor subunits, as demonstrated with a series of intramolecular exciplex emitters based on 10-phenyl-9,10-dihydroacridine and 2,4,6-triphenyl-1,3,5-triazine. Sky-blue OLEDs employing one of these emitters achieve an external quantum efficiency (EQE) of 27.4% at 67 cd m−2 with only minor efficiency roll-off (EQE = 24.4%) at a higher luminous intensity of 1,000 cd m−2. As a control experiment, devices using chemically and structurally related but less rigid emitters reach substantially lower EQEs. These design rules are transferrable to other donor/acceptor combinations, which will allow further tuning of emission colour and other key optoelectronic properties. The use of rigid linkers to control the relative position and interaction of donor and acceptor units in exciplex emitters leads to the realization of organic light-emitting devices with enhanced external quantum efficiency.

Harnessing the near-infrared (NIR) region of the electromagnetic spectrum is exceedingly important for photovoltaics, telecommunications, and the biomedical sciences. While thermally activated delayed fluorescent (TADF) materials have attracted much interest due to their intense luminescence and narrow exchange energies (ΔEST), they are still greatly inferior to conventional fluorescent dyes in the NIR, which precludes their application. This is because securing a sufficiently strong donor-acceptor (D-A) interaction for NIR emission alongside the narrow ΔEST required for TADF is highly challenging. Here, we demonstrate that by abandoning the common polydonor model in favor of a D-A dyad structure, a sufficiently strong D-A interaction can be obtained to realize a TADF emitter capable of photoluminescence (PL) close to 1000 nm. Electroluminescence (EL) at a peak wavelength of 904 nm is also reported. This strategy is both conceptually and synthetically simple and offers a new approach to the development of future NIR TADF materials.

Light-emitting carbene-metal amide complexes bearing first- and second-generation carbazole dendron ligands are reported, (AdL)M(Gn), (M = Cu and Au; Gn carbazole dendrimer generation, where n = 1 and 2; AdL = adamantyl-substituted cyclic (alkyl)(amino)carbene). The thermal stability of the complexes increases with each dendrimer generation. Cyclic voltammetry indicates that the highest occupied molecular orbital/lowest unoccupied molecular orbital energy levels are largely unaffected by the size of the dendron, while first reduction and oxidation processes show a quasi-reversible character. The gold complexes in toluene at room temperature show photoluminescent quantum yields of up to 51.5% for the first and 78% for the second generation. Varied temperature transient photoluminescence decay is consistent with a thermally activated process, indicating a delayed fluorescence-type emission mechanism. Neat films show excited state lifetimes composed of prompt and dominant sub-microsecond delayed components, with radiative constants of up to 106 s–1. Solution-processed organic light-emitting diodes for first-generation copper and gold dendrimers (AdL)M(G1) have been fabricated with external quantum efficiencies of 5.5% for copper and 10.3% for gold at practical brightness.

Current materials leaders in OLED technology are largely based on phosphorescent iridium complexes and Thermally Activated Delayed Fluorescence (TADF) materials which emit by harvesting light from all excited states ensuring nearly 100% internal quantum efficiency (IQE). Although, high efficiency red, green and blue OLEDs were realized, very short operating stability remains a fundamental challenge for blue OLEDs. Here we present our materials design strategy. We have recently designed numerous linear coinage metal complexes with efficient photo- and electroluminescent properties.[1,2] Our materials are composed of the donor and acceptor ligands which are linked by a coinage metal atom. Linear geometry of coinage metal complexes enables rotational flexibility. Rotation about the metal-ligand bond allowed us to tune the energy gap between singlet and triplet excited states. When the gap is close to zero, facile intersystem crossing and reversed intersystem crossing are possible which enables efficient singlet and triplet excited state harvesting. Depending on the value of the energy gap we have designed various functional materials with phosphorescent or delayed fluorescence properties. As a proof of concept, we fabricated OLED devices with exceptionally high external quantum efficiencies (>28% EQE) in both solution-processed and vacuum-deposited OLEDs.[3] Power and current efficiency are comparable to or exceeding state-of-the-art phosphorescent OLEDs and quantum dot LEDs. Our materials possess short excited state lifetime (100-300 ns) for the delayed emission which is highly important for the fabrication of the long-lived OLEDs. [1] A.S. Romanov, D. Di, L. Yang, J. Fernandez-Cestau, C.R. Becker, C.E. James, B. Zhu, M. Linnolahti, D. Credgington, M. Bochmann, Chem. Commun., 52, 6379 (2016) [2] A.S. Romanov, C.R. Becker, C.E. James, D. Di, D. Credgington, M. Linnolahti, M. Bochmann, Chem. Eur. J., 23, 4625 (2017). [3] D. Di, A.S. Romanov, L. Yang, J.M. Richter, J.P.H. Rivett, S. Jones, T.H. Thomas, M.A. Jalebi, R.H. Friend, M. Linnolahti, M. Bochmann, D. Credgington, Science, 356, 159 (2017)

Light emission in organic semiconductors is governed by the spin of excitons formed upon electrical excitation. Conventionally, 25% of excitons form as emissive singlets and 75% form non-emissive triplets. Exceeding this limit for OLEDs requires designing new materials. Developments in molecular design have allowed utilization of triplet excitons through either direct phosphorescence (1) or secondary processes converting a triplet into a singlet via a spin flip, creating “delayed” fluorescence. (2) Thermally Activated Delayed Fluorescence (TADF) has provided guidelines for creating donor-acceptor molecules, but the effects governing spin dynamics are still being explored. Increasingly, there is consensus that intersystem crossing,(ISC) cannot be understood from a static picture of the molecules; a more dynamic approach is necessary. Carbene Metal Amide (CMA) emitters (3) provide an excellent example, displaying large spectral shifts due to conformational reorganisation and highly variable intersystem crossing rates. In solid films, they have produced solution processed green OLEDs with record efficiencies. Here we show, starting from the green CMA archetypes, we can alter the molecular design to probe the effects of steric hindrance, spin-orbit coupling, and dipole strength on the emission properties. Using fast time resolved cryogenic PL spectroscopy we demonstrate the impact of changing the metal bridge atom on ISC, and explore high molecular weight variants for flexible electronics. We demonstrate these emitters can be tuned across the visible spectrum whilst retaining similar photophysical properties, and achieve efficient OLED devices via both solution and vacuum processing. We discuss their structure property relationships for emission, explore a new set of high efficiency OLED dopants, and provide fundamental insight into their spin conversion mechanism. From these studies we derive the first set of design rules for this new class of organometallic TADF emitters. 1) Very high-efficiency green organic light-emitting devices based on electrophosphorescence, Baldo et al. Appl. Phys. Lett. 1999 2) Highly efficient organic light-emitting diodes from delayed fluorescence. Uoyama et al. Nature 2012 3) High-performance light-emitting diodes based on carbene-metal-amides, Di et al. Science, 2017

Efficient vacuum-processed organic light-emitting diodes (OLEDs) have been fabricated using the carbene-metal-amide material CMA1. Electroluminescence external quantum efficiencies of greater than 24 % have been achieved with host-guest emissive layers utilizing a 1,3-bis(N-carbazolyl)benzene (mCP) host as well as in host-free emissive layers comprising pure CMA1. Furthermore, an external quantum efficiency greater than 26 % has been achieved by substitution of the emissive layer host for a symmetrical, non-polar variant. Electroluminescence spectra are found to depend on both emissive layer doping concentration and the choice of host material, enabling tuning of emission colour from mid-green (Commission Internationale de l’Eclairage co-ordinates [0.24, 0.46]) to sky blue ([0.22 0.35]) without changing dopant. This tuning is achieved without compromising luminescence efficiency (> 80 %) and maintaining a short radiative lifetime of triplets (< 1 µs).

A new family of cyclometallated gold(III) thiolato complexes based on pyrazine‐centred pincer ligands has been prepared, (C^Npz^C)AuSR, where C^Npz^C=2,6‐bis(4‐ButC6H4)pyrazine dianion and R=Ph (1), C6H4 tBu‐4 (2), 2‐pyridyl (3), 1‐naphthyl (1‐Np, 4), 2‐Np (5), quinolinyl (Quin, 6), 4‐methylcoumarinyl (Coum, 7) and 1‐adamantyl (8). The complexes were isolated as yellow to red solids in high yields using mild synthetic conditions. The single‐crystal X‐ray structures revealed that the colour of the deep‐red solids is associated with the formation of a particular type of short (3.2–3.3 Å) intermolecular pyrazine⋅⋅⋅pyrazine π‐interactions. In some cases, yellow and red crystal polymorphs were formed; only the latter were emissive at room temperature. Combined NMR and UV/Vis techniques showed that the supramolecular π‐stacking interactions persist in solution and give rise to intense deep‐red photoluminescence. Monomeric molecules show vibronically structured green emissions at low temperature, assigned to ligand‐based 3IL(C^N^C) triplet emissions. By contrast, the unstructured red emissions correlate mainly with a 3LLCT(SR→{(C^Npz^C)2}) charge transfer transition from the thiolate ligand to the π⋅⋅⋅π dimerized pyrazine. Unusually, the π‐interactions can be influenced by sample treatment in solution, such that the emissions can switch reversibly from red to green. To our knowledge this is the first report of aggregation‐enhanced emission in gold(III) chemistry.

Background/Aims Recent data show great benefit from beta adrenergic blocking drug (β-blocker) use in heart failure and has resulted in increased use of these established agents. Older data caution against their use in patients with reversible airways disease because of risks of bronchoconstriction. Anecdotally, we noted a difference in willingness to prescribe β-blockers by cardiologists and respiratory physicians, especially for patients with coexisting airways disease. We sought to test this difference. Methods Nine clinical scenarios were created, tested and emailed to all members of the Cardiac and Thoracic societies of Australasia. Scenarios combined varying degrees of benefit and risk (bronchoconstriction). An inducement to return questionnaires was applied. Results Cardiologists and respiratory physicians were similarly willing to prescribe β-blockers for patients at little risk of bronchoconstriction, irrespective of potential benefit. Cardiologists were more willing to prescribe β-blockers than respiratory physicians for patients at greater risk of bronchoconstriction, particularly when the potential therapeutic benefit was greater. Conclusions Our perception that cardiologists were more willing to prescribe β-blockers than respiratory physicians was confirmed. This probably results from a difference in focus (namely focus on benefit by cardiologists vs focus on risk by respiratory physicians), although other factors including awareness of limitations of pulmonary function testing by respiratory physicians may have been involved. Until better tests are available (that discriminate between patients who are likely to suffer bronchoconstriction from those who are not), it is likely that this difference between the specialties will remain.

Organic light-emitting diodes (OLEDs) promise highly efficient lighting and display technologies. We introduce a new class of linear donor-bridge-acceptor light-emitting molecules, which enable solution-processed OLEDs with near-100% internal quantum efficiency at high brightness. Key to this performance is their rapid and efficient utilization of triplet states. Using time-resolved spectroscopy, we establish that luminescence via triplets occurs within 350 nanoseconds at ambient temperature, after reverse intersystem crossing to singlets. We find that molecular geometries exist at which the singlet-triplet energy gap (exchange energy) is close to zero, so that rapid interconversion is possible. Calculations indicate that exchange energy is tuned by relative rotation of the donor and acceptor moieties about the bridge. Unlike other systems with low exchange energy, substantial oscillator strength is sustained at the singlet-triplet degeneracy point., D.D. and R.H.F. acknowledge support from the Department of Physics (Cambridge) and the King Abdulaziz City for Science and Technology–Cambridge University Joint Centre of Excellence. L.Y. thanks the Singapore Agency for Science, Technology and Research (A*STAR) for a Ph.D. studentship. J.M.R. acknowledges support from the Winton Program for the Physics of Sustainability. J.P.H.R. acknowledges the Cambridge NanoDTC (grant EP/L015978/1). M.L. acknowledges support by the Academy of Finland (project 251448). The computations were made possible by use of the Finnish Grid and Cloud Infrastructure. This work was supported by the Engineering and Physical Sciences Research Council (grant no. EP/M005143/1) and the European Research Council (ERC). M.B. is an ERC Advanced Investigator Award holder (grant no. 338944-GOCAT). D.C. and S.J. acknowledge support from the Royal Society (grant nos. UF130278 and RG140472).

Background: Cigarette smoking remains a health issue despite declining prevalence in Australia. The burden of tobacco-related morbidity affects hospitals, particularly those in lower socioeconomic areas where prevalence is highest. Aim: We have shown that nicotine replacement therapy (NRT) use during hospitalization increases motivation to quit post-discharge. We postulated that subjects using the nicotine patch post-discharge, in comparison to the inhaler, would have higher rates of abstinence at 12 months after discharge. The aim was to compare the efficacy of the nicotine patch or inhaler formulation for cessation post-discharge, following use during admission. Methods: Post-discharge, subjects chose their preferred formulation (patch or inhaler) based on their experience with NRT during admission. Tailored, medium-intensity support was provided with subsidized NRT during outpatient visits. Subjects were followed for 12 months. Exhaled breath CO confirmed non-smoking. Results: Of 123 subjects enrolled, 37 elected to use the inhaler, 50 the patch and 36 no NRT. At 12 months continuous abstinence rates were 38%, 38% and 25% respectively. Discussion: This study built upon the ‘teachable moment’ provided by hospitalization and the inpatient use of NRT, encouraging cessation post-discharge. Both NRT formulations provided similar 12 month cessation rates, and were superior to those achieved by subjects electing not to use NRT. Although the patch was the most popular formulation, the inhaler provided an equally efficacious alternative which addressed other facets of cigarette addiction. Subjects electing not to use NRT were less successful. Continuous abstinence rates were equivalent to community-based studies using NRT. We recommend a similar programme to other hospitals.

Background: A period of hospitalisation is perhaps the longest period of enforced ‘temporary abstinence’ smokers have to endure and hence many crave during their admission. Cravings may result in patients' smoking on hospital premises. Nicotine replacement may reduce cravings, decrease smoking on hospital grounds and increase interest in quitting post-discharge. Aim: The aim of this study was to compare the efficacy of two nicotine formulations in controlling inpatient cravings and enthusiasm for quitting post-discharge. Methods: Inpatients who were smokers were randomised to nicotine patch or inhaler on alternating days. Patients selected their preferred formulation, which was then used for the duration of the hospital stay. Craving control and formulation preference were assessed by visual analogue scales (VAS), and interest in quitting on a 3-point scale. Abstinence was confirmed by exhaled breath CO monitoring. Results: Patches were preferred by 64% of the 367 subjects. Fewer patients went outside to smoke after either formulation (37% before, 5% after enrolment). Cravings were reduced by both nicotine formulations (mean VAS score fell from 7.5 to 1.7). Interest in quitting post-discharge increased. Estimated mean exposure to nicotine was 5 mg/day (inhaler), 15 mg/day (transdermal patch) compared with 30 mg/day (cigarettes) before hospitalisation. Conclusions: Many smokers crave and some smoke outside during a hospital admission. While the patch was the preferred formulation of nicotine replacement therapy, both were effective in reducing cravings, increasing motivation for quitting post-discharge and improving Hospital ‘image’ by reducing smoking on campus. Nicotine replacement therapy should be made available to inpatients in all hospitals and other places of enforced prolonged abstinence.

Background: Cigarette smoking prevalence has been declining over decades in Western countries especially in higher socioeconomic groups. Employees of Australian hospitals span the socioeconomic spectrum, but there are few data on smoking prevalence from these workplaces. Because smoking is a health hazard, some argue that it should be banned on hospital premises, but employees' opinions appear not to have been widely canvassed. Cigarette smoking is a particular problem in hospitals because of the need for prolonged abstinence by immobile patients and the stressors that accompany life-and-death events for patients and/or relatives. The Queen Elizabeth Hospital has had a Stop Smoking Service for >10 years, but how smoking prevalence has changed and how it compares with similar hospitals is unknown. Aims: The aims of this study were (i) to determine smoking prevalence by employees of The Queen Elizabeth Hospital and to compare this with employees of other hospitals and (ii) to ascertain employees' perspectives regarding smoking on hospital grounds. Methods: Single page questionnaires were forwarded to employees of four South Australian/Northern Territory hospitals enquiring about smoking status, employment category, views about smoking on hospital premises, etc. Responses were voluntary. Results: Response rates were 39–59%. Smoking prevalence has steadily declined at The Queen Elizabeth Hospital and is now 8.4%. Prevalence at comparator hospitals was approximately double this value. Most staff thought the visibility of smoking was problematic, but support for providing smoking area/s was greater than for a hospital-wide ban. Conclusions: The ongoing decline in smoking prevalence at The Queen Elizabeth Hospital is probably the result of the Staff Stop Smoking Service.

Background: The coprescription of drugs which elevate cyclosporin blood concentration has been advocated to reduce the costs associated with use of this expensive immunosuppressive drug. This is the first time that drugs have been widely prescribed for an economic purpose and while it is thought to be widespread, there are little published data on the extent of this practice in Australia and New Zealand. Aims: To determine the extent to which cyclosporin sparing agents are used by Australian and New Zealand organ transplant centres, to determine which agents are used and why these agents are used by some but not all centres. Methods: Organ transplant centres were surveyed via a questionnaire. Results: Considerable variation in use of cyclosporin sparing agents exists both within and across organ transplant types by Australian and New Zealand transplant centres. Diltiazem use is more widespread than ketoconazole. Conclusions: Little of the variability in use of cyclosporin sparing agents can be explained by scientific considerations. While the central government benefits from the significant cost savings achieved by the use of cyclosporin sparing agents, individual transplant units may not. Transplant units may however be the major target in the event of litigation arising as a result of adverse effects. The availability of generic brands and improved formulations of cyclosporin may affect the viability of using cyclosporin sparing agents

Diltiazem (DTZ) is an anti-hypertensive and anti-anginal agent which is also used clinically as a metabolic inhibitor to reduce cyclosporin-A metabolism. The present communication describes an HPLC/UV method for measuring DTZ and 3 of its major metabolites. This method has a LOQ below 2.5 μg/L and within run CV's ranging from 11.3 to 1.9% at concentrations of 2.5 and 100 μg/L, and between-run CV's ranging from 10.5 to 4.9% at concentrations of 75 and 350 μg/L, respectively. The method has been applied successfully to 11 renal transplant recipients taking a variety of other drugs.

Recent data show great benefit from beta adrenergic blocking drug (β-blocker) use in heart failure and has resulted in increased use of these established agents. Older data caution against their use in patients with reversible airways disease because of risks of bronchoconstriction. Anecdotally, we noted a difference in willingness to prescribe β-blockers by cardiologists and respiratory physicians, especially for patients with coexisting airways disease. We sought to test this difference.Nine clinical scenarios were created, tested and emailed to all members of the Cardiac and Thoracic societies of Australasia. Scenarios combined varying degrees of benefit and risk (bronchoconstriction). An inducement to return questionnaires was applied.Cardiologists and respiratory physicians were similarly willing to prescribe β-blockers for patients at little risk of bronchoconstriction, irrespective of potential benefit. Cardiologists were more willing to prescribe β-blockers than respiratory physicians for patients at greater risk of bronchoconstriction, particularly when the potential therapeutic benefit was greater.Our perception that cardiologists were more willing to prescribe β-blockers than respiratory physicians was confirmed. This probably results from a difference in focus (namely focus on benefit by cardiologists vs focus on risk by respiratory physicians), although other factors including awareness of limitations of pulmonary function testing by respiratory physicians may have been involved. Until better tests are available (that discriminate between patients who are likely to suffer bronchoconstriction from those who are not), it is likely that this difference between the specialties will remain.

Dextromoramide is a narcotic analgesic drug which has been said to be clinically useful where rapid onset and short duration of action is required. The present communication describes a modification of previous high performance liquid chromatographic methods for determining plasma dextromoramide concentrations. The method described is sensitive, accurate and precise, with intra-assay CV's of 4.1%, 4.1% and 4.2% and between-assay CV's of 2.9%, 2.4% and 3.9% at concentrations of 10, 100 and 1000 μg/L, respectively. It has a limit of quantitation of 5 μg/L with a chromatographic run time of 8 min. Pharmacokinetic studies in 2 patients given 5mg of dextromoramide intravenously are presented as applications of this method. These studies showed a bi-exponential decay of dextromoramide in plasma over 24h with terminal half-lives of 3.7 and 23.5h which resulted from variability in plasma dextromoramide clearance and distribution volumes.

Cigarette smoking remains a health issue despite declining prevalence in Australia. The burden of tobacco-related morbidity affects hospitals, particularly those in lower socioeconomic areas where prevalence is highest.We have shown that nicotine replacement therapy (NRT) use during hospitalization increases motivation to quit post-discharge. We postulated that subjects using the nicotine patch post-discharge, in comparison to the inhaler, would have higher rates of abstinence at 12 months after discharge. The aim was to compare the efficacy of the nicotine patch or inhaler formulation for cessation post-discharge, following use during admission.Post-discharge, subjects chose their preferred formulation (patch or inhaler) based on their experience with NRT during admission. Tailored, medium-intensity support was provided with subsidized NRT during outpatient visits. Subjects were followed for 12 months. Exhaled breath CO confirmed non-smoking.Of 123 subjects enrolled, 37 elected to use the inhaler, 50 the patch and 36 no NRT. At 12 months continuous abstinence rates were 38%, 38% and 25% respectively.This study built upon the 'teachable moment' provided by hospitalization and the inpatient use of NRT, encouraging cessation post-discharge. Both NRT formulations provided similar 12 month cessation rates, and were superior to those achieved by subjects electing not to use NRT. Although the patch was the most popular formulation, the inhaler provided an equally efficacious alternative which addressed other facets of cigarette addiction. Subjects electing not to use NRT were less successful. Continuous abstinence rates were equivalent to community-based studies using NRT. We recommend a similar programme to other hospitals.

Digoxin remains a commonly prescribed medication for the treatment of congestive cardiac failure or atrial tachyarrhythmias. Its utility is offset by its narrow therapeutic index requiring regular blood concentration monitoring. Recent evidence suggests that a lower therapeutic range (0.5- 0.8 mg/L, or 0.6-1.0 nmol/L) is associated with reduced mortality in patients with congestive cardiac failure. Therapeutic drug monitoring for digoxin is carried out by immunoassays that are well established in routine clinical practice. Laboratories using different immunoassays may be involved in monitoring individual patients throughout the protracted course of therapy. These results should be concordant to ensure consistent dose individualization and optimum clinical management. We have investigated the discordance in digoxin measurements involving five different laboratories across the Adelaide metropolitan area.Aliquots from routine digoxin samples (n = 261) were analysed by accredited laboratories using commercially available immunoassays.The results showed that 119 (46%) of 261 samples were so varied that a different clinical outcome was indicated when reviewed by the treating physician. The differences between the highest and lowest readings from any one sample were also substantial, with 45% of the measurements exceeding 0.3 microg/L.Our study shows the considerable variation in the routine monitoring of digoxin. This makes therapeutic drug monitoring difficult to interpret and complicates clinical management when treating physicians are endeavouring to avoid toxicity and optimize dosing. These results raise a significant concern for the quality of therapeutic drug monitoring of digoxin and have direct repercussions on patient care.

Cigarette smoking prevalence has been declining over decades in Western countries especially in higher socioeconomic groups. Employees of Australian hospitals span the socioeconomic spectrum, but there are few data on smoking prevalence from these workplaces. Because smoking is a health hazard, some argue that it should be banned on hospital premises, but employees' opinions appear not to have been widely canvassed. Cigarette smoking is a particular problem in hospitals because of the need for prolonged abstinence by immobile patients and the stressors that accompany life-and-death events for patients and/or relatives. The Queen Elizabeth Hospital has had a Stop Smoking Service for10 years, but how smoking prevalence has changed and how it compares with similar hospitals is unknown.The aims of this study were (i) to determine smoking prevalence by employees of The Queen Elizabeth Hospital and to compare this with employees of other hospitals and (ii) to ascertain employees' perspectives regarding smoking on hospital grounds.Single page questionnaires were forwarded to employees of four South Australian/Northern Territory hospitals enquiring about smoking status, employment category, views about smoking on hospital premises, etc. Responses were voluntary.Response rates were 39-59%. Smoking prevalence has steadily declined at The Queen Elizabeth Hospital and is now 8.4%. Prevalence at comparator hospitals was approximately double this value. Most staff thought the visibility of smoking was problematic, but support for providing smoking area/s was greater than for a hospital-wide ban.The ongoing decline in smoking prevalence at The Queen Elizabeth Hospital is probably the result of the Staff Stop Smoking Service.

The aim of this study was to determine whether creatinine clearance can be estimated as well by clearance of gentamicin/tobramycin as by routine, non-invasive estimates in the intensive care unit. The volume of distribution and clearance values for gentamicin I tobramycin were obtained using first order kinetics and an estimate of creatinine clearance derived. Seven estimates of renal function (Cockroft-Gault, MDRD4 and MDRD6 equations, two- and 24-hour urine estimates, two equations utilising Cystatin C concentrations) were compared to the gentamicin/tobramycin clearance estimate in 100 intensive care unit patients. The gentamicin clearance estimate was at least as reliable as other estimates. The two-hour was less reliable than the 24-hour urine estimate. The Cockroft-Gault appeared to out-perform the MDRD equation estimates. The MDRD4 was not as reliable as the MDRD6 estimate. Cystatin C estimates appeared not as reliable as the gentamicin estimate of renal function. The gentamicin/tobramycin estimate is at least as good as other estimates and it is available sooner than most others. It should be used in all patients who are prescribed gentamicin. The two-hour urine and MDRD4 estimates should not be used in the intensive care unit.

A pulsed current technique for measuring the critical transport properties of superconductors as a continuous function of current or temperature is described. Greatly reduced sample heating permits investigation of both the ‘‘weak link’’ and intrinsic properties of granular superconductors. Results obtained for various high Tc oxide superconductors provide an example of the technique’s application. Both intergranular and intragranular critical current densities are extracted from the data. Current‐voltage measurements using the pulse method are corroborated by traditional dc measurements.

There is substantial information concerning the effects of continuous exposure to supratherapeutic or therapeutic concentrations of doxorubicin on human molar pulpal cells; the effects of continuous exposure to subtherapeutic concentrations of this agent are undetermined. To this end, we studied the proliferation of human fibroblasts and pulpal cells and their pattern of mineralized nodule deposition in vitro. Cell proliferation was assessed at 1, 3, 5, and 7 days from populations with either no exposure (control) or exposure to 10(-6)-10(-9) mol/L doxorubicin. Mineralized nodule deposition and calcium-45 incorporation were assessed at 7 and 21 days of culture. Data were compared by factorial ANOVA and a post-hoc Tukey test. 10(-6) and 10(-7) mol/L doxorubicin significantly reduced the total number of viable pulpal cells in cultures from days 1 to 3 (p0.05); doxorubicin 10(-6)-10(-9) mol/L significantly inhibited cell proliferation (p0.05) and DNA synthesis 5 days after plating (p0.001). After 21 days, doxorubicin 10(-6)-10(-8) mol/L significantly decreased calcium-45 incorporation into pulpal cultures (p0.001); all dilutions significantly reduced the number of mineralized nodules within the 21-day pulpal cultures (p0.05). In addition, all dilutions of doxorubicin significantly inhibited fibroblast cell proliferation and incorporation of [(3)H]thymidine. In contrast, the fibroblast cultures did not produce mineralized nodules, suggesting that the mineralized nodules within the pulpal cell cultures did not result from dystrophic calcification. Thus, exposure to subtheraputic doxorubicin concentrations has potential adverse effects on mineralized tissue formation within the pulp, which could affect the rates of reparative dentin deposition within the tooth pulps of patients receiving this chemotherapeutic agent.

Measurements of the real (χ') part of the ac magnetic susceptibility have been performed on two polycrystalline Gd2CuO4 samples sintered at different temperatures, 850°C and 1080°C in the temperature range 10

We report the results obtained by x‐ray, dc magnetization, ac magnetic susceptibility, microwave magnetic absorption, and electron paramagnetic resonance of the magnetic and superconductive properties of a large series of compounds of the form A2−x−yBxCeyCuO4 with A,B≡La, Pr, Nd, Sm, Eu, Gd, and Y. For y=0 antiferromagnetic ordering of the copper moments is present at TN≊280 K for all the compounds formed in the tetragonal T’ phase. Weak ferromagnetism (WF) associated with the canting of the copper moments is observed in all the compounds with a lattice parameter, a

Gd2-xCexCuO4, 0≤x≤0.15, have been synthesized by the solid state reaction, the sol-gel technique and the water-in-oil microemulsion, in order to vary the particle size. The samples have been characterized by x-ray diffraction, photon correlation spectroscopy and transmission electron microscopy. Magnetization and ac susceptibility measurements were performed between 4 and 300 K. The extrapolated linear part of the inverse magnetization shifts to lower temperatures as the particle size decreases. The internal field associated to the WF of the Cu moments diminishes with the particle diameter. Differences between the zero-field-cooling and the field-cooling magnetization curves were observed for T

Background: Data on prevalence of cigarette smoking by hospital employees are limited in Australia, but anecdotal evidence suggests that many health sector employees continue to smoke despite abundant evidence regarding the harmful effects of this habit. Nicotine is an addictive drug and arguably this should be known better in the health industry than in any other industry. Despite having this knowledge at their disposal, health sector employers rarely provide assistance to employees, relying instead on restrictive policies to reduce smoking in the workplace. Methods: To assist employees to quit smoking, we instituted a medium intensity Stop Smoking Programme, run by a clinical pharmacist offering nicotine patches and support on a weekly basis. A principal aim of the service was to redress the imbalance between the availability of cigarettes and the most effective nicotine replacement therapy, the trandermal nicotine patch. Following 18 months operation of this service, we surveyed hospital employees to ascertain smoking rates and views on smoking cessation in this South Australian teaching hospital. Results: In the first 18 months of operation, 111 staff members availed themselves of the service. At the first follow up period (three months), 21 were not contactable, 29 were successful in not smoking and 61 were still smoking. Six of the 29 who were not smoking at three months resumed smoking by six months, and a further four resumed smoking by 12 months. At the time of this report, 12 of the remaining 19 non smokers had completed two years since quitting and a further three of these had resumed regular smoking by this time. The cost of providing the service was modest at approximately $180.00 per known successful quitter. Results from the survey showed that 12.4% of hospital employees were regular smokers. Smoking prevalence was not equally distributed with female employees being twice as likely to smoke as their male counterparts and employees in the catering department having the highest smoking prevalence (23.8%). Conclusions: Although the prevalence of cigarette smoking by employees of this teaching hospital is lower than for the general community, health sector employers can reduce smoking prevalence further by providing assistance to their employees to quit smoking. The Stop Smoking Programme we describe is effective and could be replicated by other hospitals and similar organisations.

To consider the effect of changing from a conventional release formulation of diltiazem to the controlled diffusion diltiazem formulation on the cyclosporin-sparing effect in kidney transplant recipients.Seven stable renal transplant recipients were studied on two separate occasions following at least 2 weeks stabilisation on either formulation. The order of administration of the two formulations was not randomised as all patients were already prescribed lower dosages of diltiazem before entering this phase of a larger study. The doses of diltiazem used were 90 mg (conventional release diltiazem) taken twice daily and 180 mg controlled diffusion diltiazem taken in the morning.Whilst there were no overall significant differences between the two formulations, the study demonstrated considerable interpatient variability when changing to the controlled diffusion formulation, particularly following the morning cyclosporin dose, with three patients showing a reduced cyclosporin AUC (30-60%) and one an increased cyclosporin AUC of 36%.A change in formulation of the cyclosporin-sparing agent may result in unpredictable alterations in cyclosporin concentrations and resultant clinical sequelae.

The pharmacokinetic interaction between the calcium channel blocking drug, diltiazem (DTZ), the antifungal agent itraconazole (ICZ) and the immunosuppressive drug cyclosporin (CsA) was studied in a patient with a single lung transplant. The CsA area under curve estimations demonstrated a significant increase when ICZ was co-prescribed (5836 micrograms l-1 h vs 8159 micrograms l-1 h) but no increase when DTZ was co-prescribed with CsA (5836 micrograms l-1 h vs 5069 micrograms l-1 h). Despite widespread use as a CsA-sparing agent, DTZ does not always increase CsA concentrations.

The extent of absorption and other pharmacokinetic parameters of dextromoramide following sublingual administration were assessed in five patients receiving chronic opioid analgesia. The use of the standard 5 mg tablet formulation was associated with negligible absorption in two patients, a prolonged time to peak concentration in the other three and substantial variability in clearance. The study concluded that the standard tablet formulation cannot be recommended for sublingual use where reliable, rapid onset analgesia is required.

To quantify the magnitude of dehydration and to identify predictors of dehydration by utilizing changes in total body water (TBW), 24 male Marines were studied during an 8d moderately cold-weather (1-3 degrees C) training exercise. Training consisted of approximately 12 h/d of moderately intense activity. Variables examined included body composition, TBW, and various blood and urinary parameters indicative of hydration. Dietary food and fluid records were also maintained. Body composition changes were consistently with the high energy expenditure and insufficient energy intake. Despite a decrease in TBW, significant dehydration as assessed by blood and urinary parameters did not occur over the 8d period, therefore no relationships were found between TBW and any of the clinical indicators of dehydration. The change in TBW was reflective of a decrease in lean body mass. These data suggest that during cold-weather military field exercise, despite high activity levels and a negative energy balance, body fluid balance can be maintained when particular attention is paid to fluid intake.

Estimates of total daily energy expenditure (TDEE) by the doubly labeled water (DLW, 2H(2)18O) and intake balance (I-B) methods were compared in six male soldiers studied over 6 days that included 5 days of strenuous winter exercise at 2,500- to 3,100-m elevation. Use of body energy stores [-9.54 +/- 1.54 (SD) MJ/day or -2,280 +/- 368 kcal/day] was estimated from changes in body weight, body density (hydrodensitometry), and total body water (H(2)18O dilution). The subjects wore computerized activity monitors and kept daily records of ration consumption (9.87 +/- 3.60 MJ/day or 2,359 +/- 860 kcal/day). Accuracy of individual DLW and I-B TDEE values was estimated from the correlations of TDEE with fat-free mass (FFM) or total weight (body wt + load). The DLW and I-B estimates of TDEE differed by -12.0 to 15.2% but provided comparable estimates of group mean TDEE (DLW = 19.07 +/- 2.37 MJ/day or 4,558 +/- 566 kcal/day; I-B = 19.41 +/- 3.72 MJ/day or 4,639 +/- 889 kcal/day; P > 0.05). The DLW TDEE was correlated with both FFM (r2 = 0.89, P < 0.01, power = 0.95) and total weight (r2 = 0.95, P < 0.01, power = 0.99), whereas I-B TDEE was correlated only with total weight (r2 = 0.75, P < 0.03, power = 0.81). Under adverse field conditions the DLW method provided individual TDEE estimates that were probably more accurate than those provided by the I-B method.

In December 1990, the Wisconsin Ultraviolet Photo-Polarimeter Experiment (WUPPE) on the Astro-1 shuttle Spacelab mission obtained approximately eight hours of pioneering ultraviolet spectropolarimetric observations on more than 20 galactic and extragalactic objects. WUPPE is a 0.5 m Cassegrain telescope coupled to a Monk-Gilleson spectrometer with a magnesium fluoride polarizing beamsplitter preceded by magnesium fluoride halfwave retarders. Two spectra from 135 to 330 nm with orthogonal polarization are detected simultaneously by a pair of intensified photodiode arrays. The first flight measured for the first time the ultraviolet polarization induced by interstellar dust, the UV intrinsic polarization of the rapidly rotating `Be' stars, and the large polarization in a `hidden' active galactic nucleus. A second flight of Astro is currently scheduled for 1994.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Core samples taken from tank 101-SY at Hanford during ``window E`` were analyzed for organic and radiochemical constituents by staff of the Analytical Chemistry Laboratory at Pacific Northwest Laboratory. Westinghouse Hanford company submitted these samples to the laboratory.