The Semi-Chiral Quotient, Hyperkahler Manifolds and T-duality

We study the construction of generalized Kahler manifolds, described purely in terms of N=(2,2) semichiral superfields, by a quotient using the semichiral vector multiplet. Despite the presence of a b-field in these models, we show that the quotient of a hyperkahler manifold is hyperkahler, as in the usual hyperkahler quotient. Thus, quotient manifolds with torsion cannot be constructed by this method. Nonetheless, this method does give a new description of hyperkahler manifolds in terms of two-dimensional N=(2,2) gauged non-linear sigma models involving semichiral superfields and the semichiral vector multiplet. We give two examples: Eguchi-Hanson and Taub-NUT. By T-duality, this gives new gauged linear sigma models describing the T-dual of Eguchi-Hanson and NS5-branes. We also clarify some aspects of T-duality relating these models to N=(4,4) models for chiral/twisted-chiral fields and comment briefly on more general quotients that can give rise to torsion and give an example.Comment: 31 page

On "New Massive" 4D Gravity

We construct a four-dimensional (4D) gauge theory that propagates, unitarily, the five polarization modes of a massive spin-2 particle. These modes are described by a "dual" graviton gauge potential and the Lagrangian is 4th-order in derivatives. As the construction mimics that of 3D "new massive gravity", we call this 4D model (linearized) "new massive dual gravity". We analyse its massless limit, and discuss similarities to the Eddington-Schroedinger model.Comment: 17 pages, v2 : version published in JHE

Scale without Conformal Invariance at Three Loops

We carry out a three-loop computation that establishes the existence of scale without conformal invariance in dimensional regularization with the MS scheme in d=4-epsilon spacetime dimensions. We also comment on the effects of scheme changes in theories with many couplings, as well as in theories that live on non-conformal scale-invariant renormalization group trajectories. Stability properties of such trajectories are analyzed, revealing both attractive and repulsive directions in a specific example. We explain how our results are in accord with those of Jack & Osborn on a c-theorem in d=4 (and d=4-epsilon) dimensions. Finally, we point out that limit cycles with turning points are unlike limit cycles with continuous scale invariance.Comment: 21 pages, 3 figures, Erratum adde

N = 2 supersymmetric sigma-models and duality

For two families of four-dimensional off-shell N = 2 supersymmetric nonlinear sigma-models constructed originally in projective superspace, we develop their formulation in terms of N = 1 chiral superfields. Specifically, these theories are: (i) sigma-models on cotangent bundles T*M of arbitrary real analytic Kaehler manifolds M; (ii) general superconformal sigma-models described by weight-one polar supermultiplets. Using superspace techniques, we obtain a universal expression for the holomorphic symplectic two-form \omega^{(2,0)} which determines the second supersymmetry transformation and is associated with the two complex structures of the hyperkaehler space T*M that are complimentary to the one induced from M. This two-form is shown to coincide with the canonical holomorphic symplectic structure. In the case (ii), we demonstrate that \omega^{(2,0)} and the homothetic conformal Killing vector determine the explicit form of the superconformal transformations. At the heart of our construction is the duality (generalized Legendre transform) between off-shell N = 2 supersymmetric nonlinear sigma-models and their on-shell N = 1 chiral realizations. We finally present the most general N = 2 superconformal nonlinear sigma-model formulated in terms of N = 1 chiral superfields. The approach developed can naturally be generalized in order to describe 5D and 6D superconformal nonlinear sigma-models in 4D N = 1 superspace.Comment: 31 pages, no figures; V2: reference and comments added, typos corrected; V3: more typos corrected, published versio

Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy

We have evaluated the ability of steady-state, radially-resolved, broad-band near infrared diffuse reflectance spectroscopy to measure carbogen-induced changes in haemoglobin oxygen saturation (SO2) and total haemoglobin concentration in a rat R3230 mammary adenocarcinoma model in vivo. Detectable shifts toward higher saturations were evident in all tumours (n = 16) immediately after the onset of carbogen breathing. The SO2 reached a new equilibrium within 1 min and remained approximately constant during 200–300 s of administration. The return to baseline saturation was more gradual when carbogen delivery was stopped. The degree to which carbogen increased SO2 was variable among tumours, with a tendency for tumours with lower initial SO2 to exhibit larger changes. Tumour haemoglobin concentrations at the time of peak enhancement were also variable. In the majority of cases, haemoglobin concentration decreased in response to carbogen, indicating that increased tumour blood volume was not responsible for the observed elevation in SO2. We observed no apparent relationship between the extent of the change in tumour haemoglobin concentration and the magnitude of the change in the saturation. Near infrared diffuse reflectance spectroscopy provides a rapid, non-invasive means of monitoring spatially averaged changes in tumour haemoglobin oxygen saturation induced by oxygen modifiers. © 1999 Cancer Research Campaig

Association of the transthyretin variant V122I with polyneuropathy among individuals of African ancestry

Hereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR mutation, is found in 3-4% of individuals of African ancestry in the United States and has been associated with cardiomyopathy and heart failure. To better understand the phenotypic consequences of carrying V122I, we conducted a phenome-wide association study scanning 427 ICD diagnosis codes in UK Biobank participants of African ancestry (n = 6062). Significant associations were tested for replication in the Penn Medicine Biobank (n = 5737) and the Million Veteran Program (n = 82,382). V122I was significantly associated with polyneuropathy in the UK Biobank (odds ratio [OR] = 6.4, 95% confidence interval [CI] 2.6-15.6, p = 4.2 × 10-5), which was replicated in the Penn Medicine Biobank (OR = 1.6, 95% CI 1.2-2.4, p = 6.0 × 10-3) and Million Veteran Program (OR = 1.5, 95% CI 1.2-1.8, p = 1.8 × 10-4). Polyneuropathy prevalence among V122I carriers was 2.1%, 9.0%, and 4.8% in the UK Biobank, Penn Medicine Biobank, and Million Veteran Program, respectively. The cumulative incidence of common hATTR amyloidosis manifestations (carpal tunnel syndrome, polyneuropathy, cardiomyopathy, heart failure) was significantly enriched in V122I carriers compared with non-carriers (HR = 2.8, 95% CI 1.7-4.5, p = 2.6 × 10-5) in the UK Biobank, with 37.4% of V122I carriers having at least one of these manifestations by age 75. Our findings show that V122I carriers are at increased risk of polyneuropathy. These results also emphasize the underdiagnosis of disease in V122I carriers with a significant proportion of subjects showing phenotypic changes consistent with hATTR amyloidosis. Greater understanding of the manifestations associated with V122I is critical for earlier diagnosis and treatment

Improving outcomes for people with COPD by developing networks of general practices: evaluation of a quality improvement project in east London

BACKGROUND: Structured care for people with chronic obstructive pulmonary disease (COPD) can improve outcomes. Delivering care in a deprived ethnically diverse area can prove challenging. AIMS: Evaluation of a system change to enhance COPD care delivery in a primary care setting between 2010 and 2013 using observational data. METHODS: All 36 practices in one inner London primary care trust were grouped geographically into eight networks of 4-5 practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary group, including a respiratory specialist and the community respiratory team, developed a 'care package' for COPD management, with financial incentives based on network achievements of clinical targets and supported case management and education. Monthly electronic dashboards enabled networks to track and improve performance. RESULTS: The size of network COPD registers increased by 10% in the first year. Between 2010 and 2013 completed care plans increased from 53 to 86.5%, pulmonary rehabilitation referrals rose from 45 to 70% and rates of flu immunisation from 81 to 83%, exceeding London and England figures. Hospital admissions decreased in Tower Hamlets from a historic high base. CONCLUSIONS: Investment of financial, organisational and educational resource into general practice networks was associated with clinically important improvements in COPD care in socially deprived, ethnically diverse communities. Key behaviour change included the following: collaborative working between practices driven by high-quality information to support performance review; shared financial incentives; and engagement between primary and secondary care clinicians

Genes Selectively Up-Regulated by Pheromone in White Cells Are Involved in Biofilm Formation in Candida albicans

To mate, MTL-homozygous strains of the yeast pathogen Candida albicans must switch from the white to opaque phase. Mating-competent opaque cells then release pheromone that induces polarization, a G1 block and conjugation tube formation in opaque cells of opposite mating type. Pheromone also induces mating-incompetent white cells to become adhesive and cohesive, and form thicker biofilms that facilitate mating. The pheromone response pathway of white cells shares the upstream components of that of opaque cells, but targets a different transcription factor. Here we demonstrate that the genes up-regulated by the pheromone in white cells are activated through a common cis-acting sequence, WPRE, which is distinct from the cis-acting sequence, OPRE, responsible for up-regulation in opaque cells. Furthermore, we find that these white-specific genes play roles in white cell biofilm formation, and are essential for biofilm formation in the absence of an added source of pheromone, suggesting either an autocrine or pheromone-independent mechanism. These results suggest an intimate, complex and unique relationship between switching, mating and MTL-homozygous white cell biofilm formation, the latter a presumed virulence factor in C. albicans

JCMT POL-2 and BISTRO Survey Observations of Magnetic Fields in the L1689 Molecular Cloud

We present 850 μm polarization observations of the L1689 molecular cloud, part of the nearby Ophiuchus molecular cloud complex, taken with the POL-2 polarimeter on the James Clerk Maxwell Telescope (JCMT). We observe three regions of L1689: the clump L1689N which houses the IRAS 16293-2433 protostellar system, the starless clump SMM-16, and the starless core L1689B. We use the Davis–Chandrasekhar–Fermi method to estimate plane-of-sky field strengths of 366 ± 55 μG in L1689N, 284 ± 34 μG in SMM-16, and 72 ± 33 μG in L1689B, for our fiducial value of dust opacity. These values indicate that all three regions are likely to be magnetically transcritical with sub-Alfvénic turbulence. In all three regions, the inferred mean magnetic field direction is approximately perpendicular to the local filament direction identified in Herschel Space Telescope observations. The core-scale field morphologies for L1689N and L1689B are consistent with the cloud-scale field morphology measured by the Planck Space Observatory, suggesting that material can flow freely from large to small scales for these sources. Based on these magnetic field measurements, we posit that accretion from the cloud onto L1689N and L1689B may be magnetically regulated. However, in SMM-16, the clump-scale field is nearly perpendicular to the field seen on cloud scales by Planck, suggesting that it may be unable to efficiently accrete further material from its surroundings

Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients

BACKGROUND: In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time. METHODS: As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV(1 )94% of predicted) at three times over a three year period. RESULTS: There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV(1), MEF(75/25%VC), and MEF(25%VC). The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period. CONCLUSION: Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease