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In lung or heart-lung transplant recipients, complications as a result of pulmonary infections continue to be the most frequent causes of morbidity and mortality. This study was undertaken to identify the contributions of (1) thoracotomy, (2) interruption of lymphatic vessels and bronchial arteries, (3) transplant procedure, (4) drug-induced immunosuppression, and (5) graft allogenicity to the increased risk of pneumonia in lung transplantation. Lewis rats were inoculated with 10(5) colony-forming units of Legionella pneumophila serogroup 1 by direct instillation into the trachea after one of the following: a general anesthetic with no operation; a left thoracotomy; a left thoracotomy with pulmonary hilar stripping; an isogeneic orthotopic left lung transplant with or without immunosuppression; or an allogeneic transplant with immunosuppression with Brown-Norway rats as donors. Immunosuppression was induced with an intramuscular injection of cyclosporine (25 mg/kg of body weight) from the inoculation day to day 3. All rats were killed on day 6, and severity of infection was determined by quantitative culture of Legionella organisms in the lungs and spleen, titer of Legionella urinary antigen, differential cell count in bronchoalveolar lavage fluid, body weight loss, and gross inspection of the lung. Significant increases in lung Legionella concentration occurred as a result of the addition of pulmonary hilar stripping (from 10(5.13 +/- 0.34) in the thoracotomy group to 10(5.66 +/- 0.25) in the thoracotomy with hilar stripping group, p = 0.013) and the addition of immunosuppression (from 10(5.47 +/- 0.47) in the isogeneic transplant group to 10(6.94 +/- 0.52) in the isogeneic transplant with immunosuppression group, p = 0.00016). Thoracotomy, transplant procedures, and allogenicity itself resulted in no significant increases. The results for all other indicators paralleled those for lung culture. We conclude that the combination of drug-induced immunosuppression with lung denervation and interruption of lymphatic vessels and bronchial arteries results in the early development and increased severity of pneumonia in lung transplantation.

Complex I is the first and largest enzyme in the respiratory chain and is located in the inner mitochondrial membrane. Complex I deficiency is the most commonly reported mitochondrial disorder presenting in childhood, but the molecular basis of most cases remains elusive. We describe a patient with complex I deficiency caused by mutation of the molecular chaperone FOXRED1. A combined homozygosity mapping and bioinformatics approach in a consanguineous Iranian-Jewish pedigree led to the identification of a homozygous mutation in FOXRED1 in a child who presented with infantile-onset encephalomyopathy. Silencing of FOXRED1 in human fibroblasts resulted in reduced complex I steady-state levels and activity, while lentiviral-mediated FOXRED1 transgene expression rescued complex I deficiency in the patient fibroblasts. This FAD-dependent oxidoreductase, which has never previously been associated with human disease, is now shown to be a complex I-specific molecular chaperone. The discovery of the c.1054C>T; p.R352W mutation in the FOXRED1 gene is a further contribution towards resolving the complex puzzle of the genetic basis of human mitochondrial disease.

Long-chain-branched (LCB) polysulfones were synthesized for potential application as multifunctional ion-transport membranes. Combination of bulky and rigid monomer units with controlled levels of branching is proposed as a method to increase free volume of the polymer matrix. Increases in free volume may allow for improved ion transport decoupled from the segmental motion of the polymer backbone, especially in these high glass transition temperature materials. Increased transport in glassy materials enables multifunctional applications that require ion transport and structural rigidity. The series of novel polymers was characterized for chemical structure, thermal transitions, and molecular weight. Ionic conductivity was tested for films cast in the presence of two lithium salts.

Rejection remains a major obstacle to long-term success of pulmonary transplantation. Direct delivery of cyclosporine to lung allografts may produce better control of rejection by generating high intragraft concentrations of drug with decreased systemic delivery and toxicity. The efficacy of inhaled cyclosporine in preventing allograft rejection was compared with systemic delivery by intramuscular injections in a rat model of lung transplantation (Brown-Norway to Lewis). Group 1 animals were given no immunosuppression. Group 2 received a single i.m. injection of 25 mg/kg CsA on the day of operation while group 3 received daily doses on postoperative days 0-3. Groups 4-7 received aerosolized CsA daily for seven days. The aerosol generator produced an airborne concentration of CsA of 180 mg/m3 with a mean particle size of 0.7 mu and estimated pulmonary depositions of CsA of 0.98-3.6 mg/kg/day. Animals were killed on POD 7, and the transplanted lungs graded histologically in a blinded fashion. All control animals showed destructive grade 4 changes by POD 7. Animals receiving high-dose aerosolized CsA (groups 6 and 7) showed minimal changes with a mean rejection grade of 1.3. A single i.m. dose of CsA (group 2) failed to prevent rejection; the mean grade was 2.2. Animals given four i.m. doses of CsA had a mean grade of 1.8. Aerosolized CsA provided significantly better control of rejection than did systemic CsA (groups 6 and 7 vs. groups 2 and 3; P less than 0.0002 and less than 0.0054, respectively). Local delivery of CsA by aerosol inhalation is effective in limiting acute rejection of the rat lung allograft.

Following a conjecture of Weinbaum, we show that every nonperiodic word W W of length at least 2 in a free group has a cyclic permutation of the form UV, where each of U U and V V occur precisely once as a cyclic subword of W W and neither occurs as a cyclic subword of W − 1 {W^{ - 1}} . In fact, we prove a somewhat stronger version of this result and also give a number of applications to one-relator products of groups.

Cardiac tamponade secondary to haemopericarpatient became hypotensive again. Pressure monidium as a result of thrombolysis is a rare complicatoring showed equalisation of right atrial and pulmontion which has not been described in major thromary artery wedge pressure at 23 mmHg. The patient’s bolysis trials [1,2]. In published case reports, it is condition failed to improve. The pericardial catheter associated with anterior or anterolateral myocardial stopped draining and repeat echocardiography infarction and occurs 20–48 h post-thrombolysis showed increased residual pericardial fluid. The [3,4]. patient was taken to theatre and a moderate amount A 75-year-old man presented with a 4-h history of of clot and blood under pressure was evacuated from crushing central chest pain. He had been suffering the pericardial sac. Direct inspection of the heart from similar milder chest pain intermittently for the confirmed that free wall rupture was not present and past 2 weeks. On admission, he was in pain but there was oozing of blood from the infarct site on the haemodynamically stable. Electrocardiogram showed postero-lateral surface of the heart. He made an a postero-lateral acute myocardial infarction (Fig. uneventful recovery. He remains well at 12 months 1A). He was treated, within 20 min, with aspirin 300 post-myocardial infarction. mg and rt-PA (recombinant-tissue-plasminogen-acThis condition is difficult to differentiate from tivator) 100 mg over 90 min followed by heparin sub-acute cardiac rupture. The diagnosis is difficult to bolus of 5000 U followed by infusion of 1000 U/h. establish without surgical intervention that is also The patient became hypotensive and distressed life-saving. The condition could have been missed after 3 h. Pulses were weak with no apparent even in fatal cases unless post-mortem examination is paradox. The JVP was not raised. Heart sounds were routinely performed. soft with no murmur or rub. A transthoracic echA paradoxical increased risk of death has been ocardiogram showed a 2–3 cm pericardial effusion reported during the first 24 h after thrombolysis for and features consistent with cardiac tamponade (Fig. myocardial infarction and cardiac tamponade ac1B). The left ventricular function was satisfactory. counts for a significant minority [5]. Incidence of Pericardiocentesis was performed via left substernal primary haemopericardium among these patients is route and 400 ml of dark blood was drained with not known. Renkins et al. had raised the possibility immediate clinical improvement. A catheter was left that some early deaths following thrombolysis rein the pericardial cavity. ported as ‘cardiogenic shock’ or ‘suspected myocarTwo to three hours after the initial drainage, the dial rupture’ could have been related to unrecognised cardiac tamponade secondary to haemopericardium without cardiac rupture [3]. *Corresponding author. Tel.: 144-1253-306-966; fax: 144-1253-306966. Large infarct size, haemorrhagic infarct following

Purpose: Refractory convulsive status epilepticus in infancy and childhood is a rare emergency situation. Metabolic disorders frequently underlie this condition, in particular Alpers' disease caused by POLG1 mutations. Status epilepticus may be the first symptom. A pathognomonic electroencephalography (EEG) signature may facilitate diagnosis of Alpers' disease and allow timely avoidance of valproic acid, which is contraindicated in this disorder because it may trigger fatal liver failure. Patients: We present five patients with Alpers' disease caused by mutations in POLG1. Age of onset ranged from 7 months to 10 years. Three of the five children died after 3 to 12 months after onset of status epilepticus. Two of these had liver failure associated with use of valproic acid; liver transplantation in one child did not prevent a fatal neurologic outcome. Results: Convulsive status epilepticus was the first obvious sign of Alpers' disease in all children. All had focal clonic and complex-focal seizures; four of them developed epilepsia partialis continua. In four children, initial EEG showed unilateral occipital rhythmic high-amplitude delta with superimposed (poly)spikes (RHADS). Magnetic resonance imaging (MRI) revealed cortical and thalamic involvement in all, although there were only discrete abnormalities in one child. Metabolic investigations remained normal in three children. Conclusion: Alpers' disease is an important differential diagnosis in childhood refractory convulsive status epilepticus. Its EEG hallmark of RHADS is important for timely diagnosis, management, and counseling.

Ionic polymer transducers (IPT) are a class of devices that leverage electroactive polymers (EAP), specifically electrolyte-swollen ionomeric membranes, to perform energy conversions. Energy transformation from input to output is referred to as transduction and occurs between the electrical and mechanical domains. The present study expands on IPT investigations with a novel series of sulfonated polysulfones (sBPS), with specific interest in the effect of polymer topology on actuator performance. A hydrophilic ionic liquid was combined with a series of sBPS through a casting method to create hydrated membranes that contained target uptakes ( f ) of the diluent. The ionic liquid's hydrophilic, yet organic nature raised the issue of its degree of compatibility and miscibility with the microphase separated domains of the host ionomeric membrane. Initial studies of the ionomer - ionic liquid morphology were performed with synchrotron small angle X-ray scattering (SAXS). The effective plasticization of the membranes was identified with dynamic mechanical analysis (DMA) in terms of varied storage modulus and thermal transitions with ionic liquid uptake. Electrical impedance spectroscopy (EIS) was employed to quantify the changes in ionic conductivity for each sBPS ionomer across a range of uptake. Combined results from these techniques implied that the presence of large amounts of ionic liquid swelled the hydrophilic domains of the ionomer and greatly increased the ionic conductivity. Decreases in storage modulus and the glass transition temperature were proportional to one another but of a lesser magnitude than changes in conductivity. The present range of ionic liquid uptake for sBPS was sufficient to identify the critical uptake ( f c ) for three of the four ionomers in the series. Future work to construct IPTs with these components will use the critical uptake as a minimum allowable content of ionic liquid to optimize the balance of electrical and mechanical properties for the device components.

Ionic polymer transducers (IPT), sometimes referred to as artificial muscles, are known to generate a large bending strain and a moderate stress at low applied voltages (

Ionic polymer transducers (IPT) are devices composed of ionomeric membranes, high surface area electrodes, and ion-conducting electrolytes that are capable of electromechanical transduction. This study aims to optimize the interactions between all three of these components to design a high performance IPT with novel ionomers. Equivalent circuit modeling of impedance data allowed for estimations of IPT capacitance due to changes in the compositions of the electrodes. Various methods for control of electrolyte uptake resulted in a range of ionic conductivity when combined with novel ionomers that vary in polymer backbone architecture and charge content. Although the ionic liquid was found to dominate the magnitude of the conductivity, the pathway for uptake was significant in determination of the overall maximum values. Combination of these optimized parameters for capacitance and ionic conductivity identified design criteria for potentially high performance IPTs to investigate the benefits of these novel ionomers in electroactive devices.Copyright © 2009 by ASME

The efficacy of local delivery of aerosol cyclosporine (CsA) for prevention of lung rejection was compared with the intramuscular route (IM) in a fully allogeneic rat model (BN/LEW) of lung transplantation (LTx). Control rats (group 1, n = 6) received no CsA after LTx. Rats in group 2 (n = 10) received 4 doses of CsA in olive oil (25 mg/kg) intramuscularly starting on postoperative day (POD) 0. Group 3 (n = 9) was treated with aerosolized CsA for 3 h/day for 7 days starting on POD 0. All animals were sacrificed on POD 6. Transplanted lungs were graded histologically in a blind manner on a 0-4 scale. Control animals all showed grade 4 rejection. i.m. CsA therapy reduced lung rejection with a rejection grade of 1.8 +/- 0.35 (mean +/- SD) but was associated with a 50% incidence of pneumonia. Aerosol CsA provided better control of rejection with a rejection grade of 1.2 +/- 0.4 (group 3 vs. group 2: P less than 0.05 Wilcoxon) and none of these animals had penumonia. Trough blood levels of CsA were significantly lower in the group treated with aerosolized CsA when compared with the IM group (P less than 0.05). Therefore we conclude that: (1) aerosol CsA is effective in preventing lung allograft rejection following lung transplantation in rats, and (2) local delivery of aerosol CsA is superior to the i.m. route because better control of rejection is achieved with a lower systemic delivery of CsA.

This study expands the number of novel synthetic ionomers specifically designed for performance as ionic polymer transducers (IPT) membranes, specifically employing a highly branched sulfonated polysulfone. Control of the synthetic design, characterization, and application of the novel ionomer is intended to allow fundamental study of the effect of polymer branching on electromechanical transduction in IPTs. Fabrication methods were developed based upon the direct application process (DAP ) to construct a series of stand-alone electro des as well as full IPTs with corresponding electrode compositions. Specifically, the volumetric ratio of RuO 2 conducting particles to the novel ionomeric matrix was varied from 0 – 45 vol % in the electrodes. Electrical impedance spectroscopy was employed to determine the electrical properties and their variation with electrode compos ition separate from and in the IPT. A percolation threshold was detected for increased ionic conductiv ity of the stand-alone electrodes and th e full IPTs based on increased loading of conducting particles in the electrodes. An equivalent electr ical circuit model was applied to fit the impedance data and implicated interfacial and bulk effects contributing differently to the electrical properties of the electrodes and IPT as a whole. The fabricated IPT series was further tested for bending actuation in response to applied step voltages and represents the first demonstration of IPTs constructed with the DAP process using 100 % novel ionomer in all components. The percolation behavior extended to the bending actuation responses for strain and voltage-normalized strain rate and is useful in optimizing IPT components for maximum performance regardless of the ionomer employed. Keywords: ionic polymer transducer, direct application process, electromechanical transduction, actuator, highly branched sulfonated polysulfone, ionic liquid, IPT, IPMC

Ionic polymer transducers (IPT), sometimes referred to as artificial muscles, are known to generate a large bending strain and a moderate stress at low applied voltages (

Using proprietary technology, Discover Technologies has developed ionomeric polymer transducers that are capable of long-term operation in air. These "Plastic Muscle TM " transducers are useful as soft distributed actuators and sensors and have a wide range of applications in the aerospace, robotics, automotive, electronics, and biomedical industries. Discover Technologies is developing novel fabrication methods that allow the Plastic Muscles TM to be manufactured on a commercial scale. The Plastic Muscle TM transducers are capable of generating more than 0.5% bending strain at a peak strain rate of over 0.1 %/s with a 3 V input. Because the Plastic Muscles TM use an ionic liquid as a replacement solvent for water, they are able to operate in air for long periods of time. Also, the Plastic Muscles TM do not exhibit the characteristic "back relaxation" phenomenon that is common in water-swollen devices. The elastic modulus of the Plastic Muscle TM transducers is estimated to be 200 MPa and the maximum generated stress is estimated to be 1 MPa. Based on these values, the maximum blocked force at the tip of a 6 mm wide, 35 mm long actuator is estimated to be 19 mN. Modeling of the step response with an exponential series reveals nonlinearity in the transducers' behavior.

The goal of this paper is to construct and describe certain arithmetic subgroups of the automorphism group of a partially commutative group. More precisely, given an arbitrary finite graph $\Gamma$ we construct an arithmetic subgroup $St(L(G))$, represented as a subgroup of $GL(n,Z)$, where $n$ is the number of vertices of the graph $\Gamma$. In the last section of the paper we give a description of the decomposition of the group of automorphisms $St^{conj}(L(G))$ as a semidirect product of the group of conjugating automorphisms $Conj(G)$ and $St(L(G))$. This result is closely related to Theorem 1.4 of the paper arXiv:0710.2573v1., Comment: 24 pages, 1 figure

Ionic polymer transducers (IPT) are devices that display electromechanical transduction and have been applied extensively both as actuators and sensors. This study employs novel, highly-branched sulfonated polysulfones to investigate the contribution of polymer topology to electromechanical transduction. We assess two methods for ionic liquid uptake in the central ionomeric membrane. The effects of casting membranes in the presence of ionic liquid and swelling cast membranes in ionic liquid on film stability and ionic conductivity are examined. Casting in the presence of ionic liquid appears to cause macrophase separation of the ionic liquid from the polymer, causing limited charge transport. Overall, swelling appears to be a more stable method and achieves higher conductivity at lower uptake levels.Copyright © 2008 by ASME

Pseudoaneurysms of saphenous vein grafts are rare. We present the case of a 58-year-old man who presented with recurrent angina nine years following quadruple coronary artery bypass graft surgery in 1983. He was found to have an aneurysm arising from the ascending aorta. The patient underwent off-pump aorto-saphenous vein pseudoaneurysm resection and redo coronary artery bypass grafts.

Mitochondrial encephalomyopathies, arising from deficiencies of the electron transport chain (ETC) give rise to a wide clinical spectrum of presentation and are often progressive in nature. The aetiology of mitochondrial encephalomyopathies have yet to be fully elucidated, however, a successive loss of ETC function may contribute to the progressive nature of these disorders. The possibility arises that as a consequence of a primary impairment of ETC activity, secondary damage to the ETC may occur. In order to investigate this hypothesis, we established a model of cytochrome oxidase (Complex IV) deficiency in cultured human astrocytoma 1321N cells. Potassium cyanide (KCN, 1mM) resulted in a sustained 50% (p

BACKGROUND: Premature ovarian failure (POF) results in menopause before the age of 40. Recently, mutations in the catalytic subunit of mitochondrial DNA polymerase gamma (POLG) were shown to segregate with POF in families with progressive external ophthalmoplegia (PEO) and multiple large-scale rearrangements of mitochondrial DNA (mtDNA). METHODS AND RESULTS: A patient, mother and maternal grandmother are described, all presenting with POF and PEO. The mother developed parkinsonism in her sixth decade. Normal mtDNA sequence excluded mitochondrial inheritance. Sequence analysis of polymerase gamma revealed a dominant Y955C mutation that segregated with disease. Southern blot analysis demonstrated mtDNA depletion in fibroblasts (43% of controls). In contrast, multiple rearrangements of mtDNA were seen in skeletal muscle, consistent with the relative sparing of nuclear-encoded complex II activity compared with other respiratory chain enzymes. Immunoblotting of native gels showed that DNA polymerase gamma stability was not affected, whereas a reverse-transcriptase primer-extension assay suggested a trend towards reduced polymerase activity in fibroblasts. CONCLUSIONS: This study confirms that POLG mutations can segregate with POF and parkinsonism and demonstrates for the first time that the Y955C mutation can lead to mtDNA depletion. Future screening projects will determine the frequency with which POLG is involved in the aetiology of POF and its impact on reproductive counselling.

This article aims to give a broad overview of some of the potential targets for nitric oxide (NO) in the brain. The relevance of NO in both physiological and pathological scenarios is considerable. There is substantial evidence that neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, involve NO in their pathogenesis. Here we describe a number of cellular components which may be affected by NO, with particular relevance to neurological diseases. As the mitochondrion (in particular the electron transport chain) would appear to be of importance when considering the deleterious effects of NO, this review has a particular emphasis on that organelle. Cellular and mitochondrial antioxidants such as glutathione and ubiquinone are also discussed. In addition, the pivotal role of the astrocyte in both neuroprotection or neurodegeneration are examined.

The master curve approach was utilized to compare fracture toughness of American Society for Testing of Materials (ASTM) A285 as developed from Charpy v-notch (CVN) data and predictive statistical models. The master curves for each of the data sets were developed in accordance with American Society for Testing Materials Specification E 1921 (ASTM E1921, “Standard Test Method for Determination of Reference Temperature, T0 , for Ferritic Steels in the Transition Range”), as prescribed by American Petroleum Institute Recommended Practice 579 (API-579, “Fitness for Service”). The results indicate that predictive statistical models developed from compact tension test results express a lower fracture toughness distribution when compared to CVN data.Copyright © 2004 by ASME

The melt-dilute treatment technology is being developed to facilitate the ultimate disposition of highly enriched Al-Base DOE spent nuclear fuels in a geologic repository such as that proposed for Yucca Mountain. Currently, approximately 28 MTHM is expected to be returned to the Savannah River Site from domestic and foreign research reactors. The melt-dilute treatment technology will melt the fuel assemblies to reduce their volume and alloys them with depleted uranium to isotopically dilute the 235U concentration and reduce the potential for criticality and proliferation concerns. A critical technology element in the development of the melt-dilute process is the development of an offgas system. Experimental tests using both cesium surrogates and radioactive cesium have shown that zeolite 4A is an effective gaseous cesium trap and as a result a preliminary offgas system concept has been developed employing dry zeolite 4A absorber beds as the primary cesium trapping medium. Final, validation of this offgas concept will occur during pilot-scale irradiated testing.

The use of surgical glues in aortic surgery has gained wide popularity due to their hemostatic and tissue reinforcing properties. Reports of acute complications associated with application of glue are rare. We report the case of a 52-year-old fragile, steroid-dependent woman who developed acute intraoperative dysfunction of an aortic prosthetic valve due to use of BioGlue surgical adhesive. A brief literature review of the acute and long-term complications of the glue is presented.

Tracheopathia osteoplastica is a rare disease of the tracheobronchial tree, which is often misdiagnosed and recognised only at post-mortem. We report the case of a 66-year-old man with this condition, mistakenly thought to be suffering from chronic bronchiectasis. He underwent successful coronary artery bypass grafting for unstable angina using an off-pump technique. A case report and brief literature review is presented.

We present the case of a young lady suffering from Crohn's disease who was diagnosed as having a disabling bronchoesophageal fistula. This was mistakenly thought to be due to the Crohn's disease, and surgery was declined for fear of further complications. She required multiple admissions for frequent chest infections. At review, 5 years later for a second opinion, the fistula was deemed congenital in origin. The fistula was successfully resected, and the histology confirmed the diagnosis.

Background The mitochondrial DNA mutation m.1555A>G predisposes to permanent idiosyncratic aminoglycoside-induced deafness that is independent of dose. Research suggests that in some families, m.1555A>G may cause non-syndromic deafness, without aminoglycoside exposure, as well as reduced hearing thresholds with age (age-related hearing loss). Objectives To determine whether adults with m.1555A>G have impaired hearing, a factor that would inform the cost–benefit argument for genetic testing prior to aminoglycoside administration. Design Population-based cohort study. Setting UK. Participants Individuals from the British 1958 birth cohort. Measurements Hearing thresholds at 1 and 4 kHz at age 44–45 years; m.1555A>G genotyping. Results 19 of 7350 individuals successfully genotyped had the m.1555A>G mutation, giving a prevalence of 0.26% (95% CI 0.14% to 0.38%) or 1 in 385 (95% CI 1 in 714 to 1 in 263). There was no significant difference in hearing thresholds between those with and without the mutation. Single-nucleotide polymorphism analysis indicated that the mutation has arisen on a number of different mitochondrial haplogroups. Limitations No data were collected on aminoglycoside exposure. For three subjects, hearing thresholds could not be predicted because information required for modelling was missing. Conclusions In this cohort, hearing in those with m.1555A>G is not significantly different from the general population and appears to be preserved at least until 44–45 years of age. Unbiased ascertainment of mutation carriers provides no evidence that this mutation alone causes non-syndromic hearing impairment in the UK. The findings lend weight to arguments for genetic testing for this mutation prior to aminoglycoside administration, as hearing in susceptible individuals is expected to be preserved well into adult life. Since global use of aminoglycosides is likely to increase, development of a rapid test is a priority., Article summary Article focus Individuals who have the m.1555A>G mutation are exquisitely sensitive to rapid-onset hearing loss after receiving aminoglycosides at normal therapeutic levels. We sought to determine whether a cohort of mature individuals with the m.1555A>G mutation have hearing loss by their mid-40s because the mutation has been reported to cause later-onset less severe hearing loss in people who have never been exposed to aminoglycosides. We wished to determine whether genetic screening prior to aminoglycoside administration is justified. Key messages This study demonstrates the prevalence of m.1555A>G to be 1 in 385 (95% CI 1 in 714 to 1 in 263) in the 1958 British birth cohort, confirming that this mutation occurs frequently in Caucasian populations. The hearing of individuals with the m.1555A>G mutation is no different to that of the general population at age 44–45 years, in contrast to previous reports which suggested that hearing decreases with age in people with m.1555A>G; any such effect is not large and likely to be subject to previous ascertainment bias. These findings lend weight to the argument for genetic testing for the m.1555A>G mutation prior to aminoglycoside administration in order to prevent avoidable hearing loss. Strengths and limitations of this study Hearing data have been collected prospectively, which avoids some of the biases inherent in studies related to deafness and hearing loss. A potential limitation of the study was that data on aminoglycoside exposure were not collected.

On bounded languages and the geometry of nilpotent groups M. R. Bridson and R. H. Gilman Finitely presented groups and the finite generation of exterior powers C. J. B. Brookes Semigroup presentations and minimal ideals C. M. Campbell, E. F. Robertson, N. Ruskuc and R. M. Thomas Generalized trees and Lambda-trees I. M. Chiswell The mathematician who had little wisdom: a story and some mathematics D. E. Cohen Palindromic automorphisms of free groups D. J. Collins A freiheitssatz for certain one-relator amalgamated products B. Fine, F. Roehl and G. Rosenberger Isoperimetric functions of groups and exotic cohomology S. M. Gersten Some embedding theorems and undecidability questions for groups C. M. Gordon Some results on bounded cohomology R. I. Grigorchuk On perfect subgroups of one-relator groups J. Harlander Weight tests and hyperbolic groups G. Huck and S. Rosebrock A non-residually finite, relatively finitely presented group in the variety N2A O. G. Kharlampovich and M. V. Sapir Hierarchical decompositions, generalized Tate cohomology and groups of type FP P. H. Kropholler Tree-lattices and lattices in Lie groups A. Lubotzky Generalizations of Fibonacci numbers, groups and manifolds C. Maclachlan Knotted surfaces in the 4-sphere with no minimal Seifert manifolds T. Maeda The higher geometric invariants of modules over Noetherian group rings H. Meinert On calculation of width in free groups A. Yu Ol'shanskii Hilbert modular groups and isoperimetric inequalities C. Pittet On systems of equations in free groups A. A. Razborov Cogrowth and essentiality in groups and algebras A. Rosenmann Regular geodesic languages for 2-step nilpotent groups M. Stoll Finding indivisible Nielsen paths for a train track map E. C. Turner More on Burnside's problem E. Zelmanov Problem session.

We report on the successful surgical resection of a mediastinal malignant triton tumor of the vagus, an exceedingly rare tumor in this location. Malignant triton tumor is a subtype of malignant peripheral nerve sheath tumors, in which the characteristic histologic finding is of rhabdomyoblastic differentiation among schwannoma cells. A 35-year-old man with associated neurofibromatosis type-1 underwent surgical resection and has been followed up for 18 months.

Rationale for the study Cardiomyopathy is an increasingly recognised presentation of mitochondrial disease in infancy. This may be an isolated finding or part of a wider multisystem disease presentation. Isolated deficiency of respiratory chain complex I is the most commonly identified biochemical defect in paediatric mitochondrial disease. Here we used a candidate gene and homozygosity mapping approach to identify the causative gene defect in two children with complex I deficiency and cardiomyopathy. Methodology Complex I assembly was investigated in a cohort of children with isolated complex I deficiency using Blue Native polyacrylamide gel electrophoresis (BN-PAGE). An integrative genomics approach, combining homozygosity mapping and candidate gene and bioinformatics analyses, was used to search for the presumed nuclear gene defect in these patients. Results BN-PAGE analysis provided evidence of defective assembly of the complex I holoenzyme in several patients. Two patients were shown to have cardiomyopathy caused by mutations in two different complex I assembly factor genes. The mutations segregated with disease in each family and were absent in >200 control alleles. Western blot analysis demonstrated reduced steady-state level of the mutated proteins, and lentiviral rescue was used to confirm the genetic defect in one case. Conclusions Mitochondrial complex I deficiency is an important cause of infantile-onset cardiomyopathy. This disorder is extremely genetically heterogeneous, but identification of the precise genetic defect is important, since this will inform treatment options, provide more accurate information regarding recurrence risks, and allow prevention of further cases by prenatal or preimplantation genetic diagnosis.

The simple reverse mounting of an Octopus arm over a rib retractor can give more arm length by up to 5 cm inside the chest cavity which could prove to be very useful in patients with huge chest cavities, i.e. chronic obstructive pulmonary disease, high body mass index, allowing more flexibility and better maneuverability of the stabilizer arm during MIDCAB.