Prevalence and risk factors for gingivitis in a cohort of UK companion cats aged up to 6 years.

OBJECTIVES: Prospectively collected data were used to estimate the prevalence of gingivitis in a cohort of companion cats aged up to 6 years and to investigate factors associated with the risk of gingivitis in cats aged 3 to 4 years. MATERIALS AND METHODS: Data were obtained from a longitudinal study of domestic cats (the Bristol Cats Study), using owner-completed questionnaires and veterinary surgeon-completed oral health scores. Prevalence estimates of veterinary-reported gingivitis for cats aged up to 6 years old (n = 1534) were calculated for different age groups. Cat signalment, diet and dental care were assessed for association with gingivitis in cats aged 3 to 4 years (n = 317) using univariable and multiple logistic regression. RESULTS: The prevalence of gingivitis increased with age and ranged from 24.5% (<12 months old) to 56.3% (5 to 6 years old). Odds of gingivitis in cats aged 3 to 4 years were higher in cats fed a wet only or mixed wet/dry diet compared to dry only (odds ratio: 2.7; 95% confidence interval: 1.4 to 5.1), cats not reported to hunt compared to reported hunters (odds ratio: 2.1; 95% confidence interval: 1.0 to 4.2), cats reported to dribble whilst being stroked at age 6 months compared to reported non-dribblers (odds ratio: 3.2; 95% confidence interval: 1.3 to 8.4) and cats with orange variants in their coat colour compared to non-orange cats (odds ratio: 2.3; 95% confidence interval: 1.0 to 5.3). CLINICAL SIGNIFICANCE: These results will help veterinary surgeons identify cats that may be at a greater risk of gingivitis and provide an evidence base to inform dietary and oral healthcare recommendations aimed at promoting gingival health in cats.

Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics.

G protein-coupled receptor (GPCR) activation initiates signalling via a complex network of intracellular effectors that combine to produce diverse cellular and tissue responses. Although we have an advanced understanding of the proximal events following receptor stimulation, the molecular detail of GPCR signalling further downstream often remains obscure. Unravelling these GPCR-mediated signalling networks has important implications for receptor biology and drug discovery. In this context, phosphoproteomics has emerged as a powerful approach for investigating global GPCR signal transduction. Here, we provide a brief overview of the phosphoproteomic workflow and discuss current limitations and future directions for this technology. By highlighting some of the novel insights into GPCR signalling networks gained using phosphoproteomics, we demonstrate the utility of global phosphoproteomics to dissect GPCR signalling networks and to accelerate discovery of new targets for therapeutic development.

Density functional theory explorations of parathion and paraoxon hydrolysis as a function of the underlying alkaline environment.

Parathion, a once commonly used pesticide known for its potential toxicity, can follow several degradation mechanisms in the environment. Given the species stability and persistence, parathion can be washed into waterways from rain, and therefore an atomistic perspective of the hydrolysis of parathion, and its byproduct paraoxon, is required in order to understand its fate in the environment. Experimental studies have determined that pH plays an important role in the calculated hydrolysis rate constants of parathion degradation. In this work, the degradation of parathion into either paraoxon or 4-nitrophenol, and the degradation of paraoxon to 4-nitrophenol are explored through density functional theory using the M06-2X functional. How the level of basicity affects the reaction mechanism is explored through two different hydroxide/water environments. Our calculations support the anticipated mechanisms determined by previous experimental work that the formation of 4-nitrophenol is the predominant pathway in hydrolysis of parathion.

Ligamentization and Remnant Integration: Review and Analysis of Current Evidence and Implications for Scapholunate Reconstruction.

Background Scapholunate interosseous ligament injuries are common but remain a therapeutic challenge. Current treatment modalities prioritize restoration of normal anatomy with reconstruction where appropriate. To date no reconstructive technique has been described that discusses the potential benefit of preservation of the scapholunate ligament remnant. Little is known about the "ligamentization" of grafts within the wrist. However, a growing body of knee literature suggests that remnant sparing may confer some benefit. In the absence of wrist specific studies, this literature must guide areas for potential augmentation of current surgical practices. Objective The purpose of this study was to perform a review of the process of ligamentization and a systematic review of the current literature on the possible role of ligament sparring and its effect on ligamentization. Methods A systematic search of the literature was performed to identify all the studies related to remnant sparing and the ligamentization of reconstructed tendons, regardless of graft type or joint involved from MEDLINE, EMBASE, and PubMed until February 1, 2016 using the following keywords: ligamentization, graft, remodelling, reconstruction, biomechan*, histolo∗, scapholunate ligament. Each selected study was evaluated for methodological quality and risk of bias according to a modified Systematic Review Center for Laboratory Animal Experimentation criteria. Conclusions The available literature suggests that ligament sparring demonstrated a trend toward improvements in vascularity, mechanoreceptors, and biomechanics that lessens in significance over time. Clinical Relevance This review suggests that remnant sparing may be one way to improve outcomes of scapholunate ligament reconstructive surgery. Level of Evidence This is a level I/II, review study.

Computational Investigation on Electronic Structures and Properties of 4,6-Bis(nitroimino)-1,3,5-triazinan-2-one: An Insensitive Munition Compound.

In order to minimize unintentional detonation, munitions researchers have focused on the development of chemical compounds that are insensitive to external stimuli while maintaining their effectiveness. Although these compounds, known as high-performance insensitive munition compounds, are promising in terms of potency and stability, their environmental impacts have either not been fully understood or are yet to be investigated. In the present research, we have performed a quantum chemical investigation on electronic structures and properties of an insensitive munition compound 4,6-bis(nitroimino)-1,3,5-triazinan-2-one (DNAM). The density functional theory using the B3LYP and M06-2X functionals and MP2 methodology were used for geometry optimization of various tautomeric forms of DNAM. The effect of bulk water solution was evaluated using the conductor-like polarizable continuum model and the density-based solvation model. Ionization potentials, electron affinities, redox properties, and p Ka values were also computed and compared with the available experimental data. These physical and chemical properties of DNAM have been discussed with regard to the varying tautomeric forms in which DNAM can exist.

Emerging infectious disease outbreaks: estimating disease risk in Australian blood donors travelling overseas.

BACKGROUND AND OBJECTIVES: International travel assists spread of infectious pathogens. Australians regularly travel to South-eastern Asia and the isles of the South Pacific, where they may become infected with infectious agents, such as dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses that pose a potential risk to transfusion safety. In Australia, donors are temporarily restricted from donating for fresh component manufacture following travel to many countries, including those in this study. We aimed to estimate the unmitigated transfusion-transmission (TT) risk from donors travelling internationally to areas affected by emerging infectious diseases. MATERIALS AND METHODS: We used the European Up-Front Risk Assessment Tool, with travel and notification data, to estimate the TT risk from donors travelling to areas affected by disease outbreaks: Fiji (DENV), Bali (DENV), Phuket (DENV), Indonesia (CHIKV) and French Polynesia (ZIKV). RESULTS: We predict minimal risk from travel, with the annual unmitigated risk of an infected component being released varying from 1 in 1·43 million to <1 in one billion and the risk of severe consequences ranging from 1 in 130 million to <1 in one billion. CONCLUSION: The predicted unmitigated likelihood of infection in blood components manufactured from donors travelling to the above-mentioned areas was very low, with the possibility of severe consequences in a transfusion recipient even smaller. Given the increasing demand for plasma products in Australia, the current strategy of restricting donors returning from select infectious disease outbreak areas to source plasma collection provides a simple and effective risk management approach.

Hepatitis E virus RNA in Australian blood donors: prevalence and risk assessment.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is a known transfusion-transmissible agent. HEV infection has increased in prevalence in many developed nations with RNA detection in donors as high as 1 in 600. A high proportion of HEV infections are asymptomatic and therefore not interdicted by donor exclusion criteria. To manage the HEV transfusion-transmission (TT) risk some developed nations have implemented HEV RNA screening. In Australia, HEV is rarely notified; although locally acquired infections have been reported, and the burden of disease is unknown. The purpose of this study was to determine the frequency of HEV infection in Australian donors and associated TT risk. MATERIALS AND METHODS: Plasma samples (n = 74 131) were collected from whole blood donors during 2016 and screened for HEV RNA by transcription-mediated amplification (TMA) in pools of six. Individual TMA reactive samples were confirmed by RT-PCR and, if positive, viral load determined. Prevalence data from the study were used to model the HEV-TT risk. RESULTS: One sample in 74 131 (95% CI: 1 in 1 481 781 to 1 in 15 031) was confirmed positive for HEV RNA, with an estimated viral load of 180 IU/ml, which is below that typically associated with TT. Using a transmission-risk model, we estimated the risk of an adverse outcome associated with TT-HEV of approximately 1 in 3·5 million components transfused. CONCLUSION: Hepatitis E virus viremia is rare in Australia and lower than the published RNA prevalence estimates of other developed countries. The risk of TT-HEV adverse outcomes is negligible, and HEV RNA donor screening is not currently indicated.

Psi4 1.1: An Open-Source Electronic Structure Program Emphasizing Automation, Advanced Libraries, and Interoperability.

Psi4 is an ab initio electronic structure program providing methods such as Hartree-Fock, density functional theory, configuration interaction, and coupled-cluster theory. The 1.1 release represents a major update meant to automate complex tasks, such as geometry optimization using complete-basis-set extrapolation or focal-point methods. Conversion of the top-level code to a Python module means that Psi4 can now be used in complex workflows alongside other Python tools. Several new features have been added with the aid of libraries providing easy access to techniques such as density fitting, Cholesky decomposition, and Laplace denominators. The build system has been completely rewritten to simplify interoperability with independent, reusable software components for quantum chemistry. Finally, a wide range of new theoretical methods and analyses have been added to the code base, including functional-group and open-shell symmetry adapted perturbation theory, density-fitted coupled cluster with frozen natural orbitals, orbital-optimized perturbation and coupled-cluster methods (e.g., OO-MP2 and OO-LCCD), density-fitted multiconfigurational self-consistent field, density cumulant functional theory, algebraic-diagrammatic construction excited states, improvements to the geometry optimizer, and the "X2C" approach to relativistic corrections, among many other improvements.

Evaluation of point-of-care maternal glucose measurements for the diagnosis of gestational diabetes mellitus.

OBJECTIVE: Using updated laboratory standards as the reference, we aimed to compare point-of-care (POC) maternal capillary glucose testing with the diagnostic accuracy of reference and customary venous samples. DESIGN, SETTING, POPULATION: Women screened selectively with a one-step 75-g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation were conveniently recruited to this prospective observational study. METHODS: Two venous samples and one capillary sample were taken at each OGTT time point. Venous sample one was a fluoride-EDTA (FE) tube placed on an ice-slurry until cell separation and analysis within 30 minutes (reference standard). Venous sample two was transported in a tube containing FE (without ice) (customary practice). A capillary sample was used for POC testing. Various cut-off points for the POC sample were examined to evaluate diagnostic accuracy. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive and negative predictive values and accuracy of POC capillary glucose for the diagnosis of GDM. RESULTS: Of 108 women, GDM was detected in 47.2% (n = 51), 17.6% (n = 19) and 24.1% (n = 26) using the reference standard, customary practices and POC, respectively (P < 0.001). However, based on adjustment of the POC fasting diagnostic threshold from ≥5.1 to ≥4.8 mol/l (aPOC), sensitivity, specificity, PPV, NPV and accuracy improved to 92.5, 76.5, 69.8, 94.5 and 94.5%, respectively. CONCLUSIONS: POC capillary maternal glucose tests were superior to customary laboratory practices for diagnosing GDM. This has considerable potential, particularly in healthcare settings where facilities for phlebotomy are distant from the laboratory or pre-analytical sample handling is substandard. TWEETABLE ABSTRACT: Adjusted point-of-care glucose measurements have potential in the diagnosis of gestational diabetes mellitus.

Idiopathic Fibrosis of the Tunica Muscularis of the Large Intestine in Five Horses with Colic.

Histological evidence of fibrosis affecting the outer layer of the large intestinal tunica muscularis was identified in five of 32 horses affected by colic. In three cases, foci of pale eosinophilia and vacuolation of myocytes were observed. These findings are suggestive of a degenerative and fibrotic abnormality in the outer layer of the tunica muscularis of the large intestinal smooth muscle of some horses with colic.

A Comparison of Three Approaches to the Reduced-Scaling Coupled Cluster Treatment of Non-Resonant Molecular Response Properties.

We have investigated the performance of the reduced-scaling coupled cluster method based on projected atomic orbitals (PAOs), pair natural orbitals (PNOs), and orbital specific virtuals (OSVs) for the prediction of linear response properties. These methods introduce different degrees of controllable sparsity in the ground-state and perturbed coupled cluster wave functions, leading to localization errors in properties such as dynamic polarizabilities and specific optical rotations. Using a series of chiral test compounds, we find that the inherent costs associated with computing response properties are significantly greater than those for determining the ground-state energy. As the dimensionality of the molecular system increases-from (pseudo)linear structures, such as fluoroalkanes, to cagelike structures, such as ß-pinene-the crossover point between canonical-orbital and localized-orbital algorithms increases substantially. Furthermore, both the OSV and PNO methods provide greater reduction in cost (as measured by the size of the double-excitation space) than do PAOs, and PNOs provide the greatest level of sparsity for the systems examined here. Single-excitation truncation induces much larger errors than corresponding doubles truncation due to the fact that the first-order contribution to the one-electron perturbed wave function appears in the singles amplitudes. Both the PNO and OSV methods perform reasonably well for frequency-dependent polarizabilities provided appropriate thresholds are used for the occupation-number and weak-pair cutoffs on which each method depends. Specific rotations, however, are very sensitive to wave function truncation, to the extent that aggressive thresholds can yield the incorrect sign of the rotation, due to the delicate balance of positive and negative wave function contributions to the mixed electric-/magnetic-field response.

Evaluation of the Pulmonary Toxicity of Ambient Particulate Matter From Camp Victory, Iraq.

Anecdotal reports in the press and epidemiological studies suggest that deployment to Iraq and Afghanistan may be associated with respiratory diseases and symptoms in U.S. military personnel and veterans. Exposures during military operations were complex, but virtually all service members were exposed to high levels of respirable, geogenic dust. Inhalation of other dusts has been shown to be associated with adverse health effects, but the pulmonary toxicity of ambient dust from Iraq has not been previously studied. The relative toxicity of Camp Victory dust was evaluated by comparing it to particulate matter from northern Kuwait, a standard U.S. urban dust, and crystalline silica using a single intratracheal instillation in rats. Lung histology, protein levels, and cell counts were evaluated in the bronchoalveolar lavage fluid 1-150 d later. The Iraq dust provoked an early significant, acute inflammatory response. However, the level of inflammation in response to the Iraq dust, U.S. urban dust, and Kuwait dust rapidly declined and was nearly at control levels by the end of the study At later times, animals exposed to the Iraq, U.S. urban, or Kuwait dusts showed increased small airway remodeling and emphysema compared to silica-exposed and control animals without evidence of fibrosis or premalignant changes. The severity and persistence of pulmonary toxicity of these three dusts from the Middle East resemble those of a U.S. urban dust and are less than those of silica. Therefore, Iraq dust exposure is not highly toxic, but similar to other poorly soluble low-toxicity dusts.

Simulation of circularly polarized luminescence spectra using coupled cluster theory.

We report the first computations of circularly polarized luminescence (CPL) rotatory strengths at the equation-of-motion coupled cluster singles and doubles (EOM-CCSD) level of theory. Using a test set of eight chiral ketones, we compare both dipole and rotatory strengths for absorption (electronic circular dichroism) and emission to the results from time-dependent density-functional theory (TD-DFT) and available experimental data for both valence and Rydberg transitions. For two of the compounds, we obtained optimized geometries of the lowest several excited states using both EOM-CCSD and TD-DFT and determined that structures and EOM-CCSD transition properties obtained with each structure were sufficiently similar that TD-DFT optimizations were acceptable for the remaining test cases. Agreement between EOM-CCSD and the Becke three-parameter exchange function and Lee-Yang-Parr correlation functional (B3LYP) corrected using the Coulomb attenuating method (CAM-B3LYP) is typically good for most of the transitions, though agreement with the uncorrected B3LYP functional is significantly worse for all reported properties. The choice of length vs. velocity representation of the electric dipole operator has little impact on the EOM-CCSD transition strengths for nearly all of the states we examined. For a pair of closely related ß, γ-enones, (1R)-7-methylenebicyclo[2.2.1]heptan-2-one and (1S)-2-methylenebicyclo[2.2.1]heptan-7-one, we find that EOM-CCSD and CAM-B3LYP agree with the energetic ordering of the two possible excited-state conformations, resulting in good agreement with experimental rotatory strengths in both absorption and emission, whereas B3LYP yields a qualitatively incorrect result for the CPL signal of (1S)-2-methylenebicyclo[2.2.1]heptan-7-one. Finally, we predict that one of the compounds considered here, trans-bicyclo[3.3.0]octane-3,7-dione, is unique in that it exhibits an achiral ground state and a chiral first excited state, leading to a strong CPL signal but a weak circular dichroism signal.

Incremental evaluation of coupled cluster dipole polarizabilities.

In this work we present the first implementation of the incremental scheme for coupled cluster linear-response frequency-dependent dipole polarizabilities. The implementation is fully automated and makes use of the domain-specific basis set approach. The accuracy of the approach is determined on the basis of a test suite of 47 molecules and small clusters. The local approximation in the coupled cluster singles and doubles polarizability exhibits a mean error of 0.02% and a standard deviation of 0.32% when using a third-order incremental expansion. With the proposed approach, it is possible to compute polarizabilities with larger basis sets compared to the canonical implementation and thus it is possible to obtain higher total accuracy. The incremental scheme yields the smallest errors for weakly-bound and quasi-linear systems, while two- and three-dimensional (cage-like) structures exhibit somewhat larger errors as compared to the full test set.

Paediatric nephrology: the last 50 years.

In 1965, the specialty of paediatric nephrology was in its infancy. Following the development of a landmark collaborative research study, the International Study of Kidney Disease in Childhood in the mid-1960s, the first specialist societies were formed: the European Society of Pediatric Nephrology in 1967 and the American Society of Pediatric Nephrology in 1969. The extraordinary improvements in care delivered to children with kidney disease over the past 50 years are too broad to cover in any one paper. They traverse the spectrum of diagnosis, classification, therapeutics, social well-being and transition to adult care. We have selected four case scenarios to highlight these changes in key areas of paediatric nephrology: post-streptococcal glomerulonephritis, nephrotic syndrome, haemolytic uraemic syndrome and neonatal dialysis and childhood transplantation.

Proton-pump inhibitors in patients requiring antiplatelet therapy: new FDA labeling.

Proton-pump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper gastrointestinal bleeding. Proton-pump inhibitors should also be considered for patients receiving antiplatelet therapy who have other risk factors for gastrointestinal bleeding, including use of aspirin. Thus, evidence of pharmacokinetic and pharmacodynamic interactions between PPIs and consequent impaired effectiveness of the antiplatelet agent clopidogrel has caused concern. Here, we discuss comparative studies suggesting that the extent to which a PPI reduces exposure to the active metabolite of clopidogrel and attenuates its antithrombotic effect differs among PPIs. Although a clinically meaningful effect of the interaction between PPIs and clopidogrel on cardiovascular outcomes has not been established, these studies provided the basis for recent changes in US Food and Drug Administration (FDA) labeling for several PPIs and clopidogrel. New labeling suggests that PPI use among patients taking clopidogrel be limited to pantoprazole, rabeprazole, lansoprazole, or dexlansoprazole. Because comparative studies indicate that omeprazole and esomeprazole have a greater effect on the CYP2C19-mediated conversion of clopidogrel to its active metabolite and, consequently, clopidogrel's effect on platelet reactivity, FDA labeling recommends avoiding omeprazole and esomeprazole in patients taking clopidogrel. Even a 12-hour separation of dosing does not appear to prevent drug interactions between omeprazole and clopidogrel.

Phylogenetic analysis of feline coronavirus strains in an epizootic outbreak of feline infectious peritonitis.

BACKGROUND: Feline coronavirus (FCoV) infection is common. In a small percentage of cats, FCoV infection is associated with the fatal disease feline infectious peritonitis (FIP). Genetically distinct virulent and avirulent strains of FCoV might coexist within a cat population. OBJECTIVES: To determine whether the strains of FCoV in FIP-affected cats are closely related or genetically distinct from the fecally derived strains of FCoV in contemporary-asymptomatic cats during an epizootic outbreak of FIP. ANIMALS: Four cats euthanized because of FIP and 16 asymptomatic cats. METHODS: This prospective outbreak investigation was initiated during an outbreak of FIP in cats within or rehomed from a rescue/rehoming center. Postmortem samples were collected from cats with FIP and contemporaneous fecal samples from asymptomatic cats. RNA was purified from tissue and fecal samples, FCoV gene fragments were reverse transcribed, PCR-amplified using novel primers, and sequenced. Sequences were aligned with ClustalW and compared with published FCoV sequences. RESULTS: FCoV RNA was detected in all 4 FIP cat postmortem samples and in 9 of the 16 fecal samples from contemporary-asymptomatic cats. Novel primers successfully amplified fragments from 4 regions of the genome for all FCoV-positive samples. Phylogenetic analysis showed that the FIP-associated strains of FCoV from the outbreak were very closely related to the fecally derived strains of FCoV from contemporary-asymptomatic cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Sequence analysis provided no evidence that genetically distinct virulent and avirulent strains of FCoV were present during this FIP outbreak.

Malaria antibody persistence correlates with duration of exposure.

BACKGROUND AND OBJECTIVES: In Australia, the risk of transfusion-transmitted malaria is managed through the identification of 'at-risk' donors, antibody screening enzyme-linked immunoassay (EIA) and, if reactive, exclusion from fresh blood component manufacture. Donor management depends on the duration of exposure in malarious regions (>6 months: 'Resident', <6 months: 'Visitor') or a history of malaria diagnosis. We analysed antibody testing and demographic data to investigate antibody persistence dynamics. To assess the yield from retesting 3 years after an initial EIA reactive result, we estimated the proportion of donors who would become non-reactive over this period. MATERIALS AND METHODS: Test results and demographic data from donors who were malaria EIA reactive were analysed. Time since possible exposure was estimated and antibody survival modelled. RESULTS: Among seroreverters, the time since last possible exposure was significantly shorter in 'Visitors' than in 'Residents'. The antibody survival modelling predicted 20% of previously EIA reactive 'Visitors', but only 2% of 'Residents' would become non-reactive within 3 years of their first reactive EIA. CONCLUSION: Antibody persistence in donors correlates with exposure category, with semi-immune 'Residents' maintaining detectable antibodies significantly longer than non-immune 'Visitors'.

Localized optimized orbitals, coupled cluster theory, and chiroptical response properties.

The impact of orbital localization on the efficiency and accuracy of the optimized-orbital coupled cluster model is examined for the prediction of chiroptical properties, in particular optical rotation. The specific rotations of several test cases-(P)-[4]triangulane, (S)-1-phenylethanol, and chiral conformers of 1-fluoropentane, heptane, and nonane-were computed using an approach in which localization is enforced throughout the orbital optimization and subsequent linear response computation. This method provides a robust local-correlation scheme for future production-level implementation. Although the cross-over point between the canonical and localized coupled cluster approach lies at larger molecules than for ground-state energies, the scheme presented should still provide reduced scaling sufficient to investigate much larger molecules than are presently accessible.

Laryngeal transplantation in minipigs: early immunological outcomes.

Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus. There were only small changes in expression of some molecules (relative to interindividual variation) and these were clearest in samples from the subglottic region, where the areas of co-expression of CD25(+) CD45RC(-) CD8(-) and of CD163(+) CD172(+) MHC-II(-) increased at 1 week after transplant. In one case, infiltration by recipient T cells was analysed by T cell receptor (TCR) Vß spectratype analysis; this suggested that changes in the T cell repertoire occur in the donor subglottis mucosal tissues from day 0 to day 7, but that the donor and recipient mucosal Vß repertoires remain distinct. The observed lack of strong immunological responses to the trauma of surgery and ischaemia provides encouraging evidence to support clinical trials of laryngeal transplantation, and a basis on which to interpret future studies involving mismatches.