Recognising anxiety and post-traumatic stress disorder in cardiac patients

Research has established that anxiety and post-traumatic stress disorder (PTSD) are risk factors for the development of heart disease in healthy populations. In addition, anxiety and PTSD are associated with further morbidity in people with existing heart disease. This article considers whether anxiety and PTSD influence onset and recovery from heart disease. Clinical implications for cardiac nursing are considered, including screening, treatment, and referral on to specialist services

Learning safely from error: Reconsidering the ethics of simulation-based medical education through ethnography

‘Human factors’ is an influential rationale in the UK national health service to understand mistakes, risk and safety. Although there have been studies examining its implications in workplaces, there has been little investigation of how it is taught, as a form of professional morality. This article draws on an observational study of human factors teaching in four hospital simulation centres in London, UK. Its main argument is that the teaching of human factors is realised through an identification and positive evaluation of ‘non-technical skills’ and the espousal of ‘non-judgemental’ pedagogy, both of which mean that mistakes cannot be made. Professional solidarity is then maintained on the absence of mistakes. We raise questions about the ethics of this teaching. The study is situated within a history of ethnographic accounts of medical mistakes, to explore the relationship between claims to professional knowledge and claims about failure

Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells

Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34<sup>+</sup>38<sup>lo</sup>) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells <i>in vitro</i>. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34<sup>+</sup> cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease

A Double Sigma Model for Double Field Theory

We define a sigma model with doubled target space and calculate its background field equations. These coincide with generalised metric equation of motion of double field theory, thus the double field theory is the effective field theory for the sigma model.Comment: 26 pages, v1: 37 pages, v2: references added, v3: updated to match published version - background and detail of calculations substantially condensed, motivation expanded, refs added, results unchange

On the Riemann Tensor in Double Field Theory

Double field theory provides T-duality covariant generalized tensors that are natural extensions of the scalar and Ricci curvatures of Riemannian geometry. We search for a similar extension of the Riemann curvature tensor by developing a geometry based on the generalized metric and the dilaton. We find a duality covariant Riemann tensor whose contractions give the Ricci and scalar curvatures, but that is not fully determined in terms of the physical fields. This suggests that \alpha' corrections to the effective action require \alpha' corrections to T-duality transformations and/or generalized diffeomorphisms. Further evidence to this effect is found by an additional computation that shows that there is no T-duality invariant four-derivative object built from the generalized metric and the dilaton that reduces to the square of the Riemann tensor.Comment: 36 pages, v2: minor changes, ref. added, v3: appendix on frame formalism added, version to appear in JHE

Ramond-Ramond Cohomology and O(D,D) T-duality

In the name of supersymmetric double field theory, superstring effective actions can be reformulated into simple forms. They feature a pair of vielbeins corresponding to the same spacetime metric, and hence enjoy double local Lorentz symmetries. In a manifestly covariant manner --with regard to O(D,D) T-duality, diffeomorphism, B-field gauge symmetry and the pair of local Lorentz symmetries-- we incorporate R-R potentials into double field theory. We take them as a single object which is in a bi-fundamental spinorial representation of the double Lorentz groups. We identify cohomological structure relevant to the field strength. A priori, the R-R sector as well as all the fermions are O(D,D) singlet. Yet, gauge fixing the two vielbeins equal to each other modifies the O(D,D) transformation rule to call for a compensating local Lorentz rotation, such that the R-R potential may turn into an O(D,D) spinor and T-duality can flip the chirality exchanging type IIA and IIB supergravities.Comment: 1+37 pages, no figure; Structure reorganized, References added, To appear in JHEP. cf. Gong Show of Strings 2012 (http://wwwth.mpp.mpg.de/members/strings/strings2012/strings_files/program/Talks/Thursday/Gongshow/Lee.pdf

Background Field Equations for the Duality Symmetric String

This paper describes the background field equations for strings in T-duality symmetric formalisms in which the dimension of target space is doubled and the sigma model supplemented with constraints. These are calculated by demanding the vanishing of the beta-functional of the sigma model couplings in the doubled target space. We demonstrate the equivalence with the background field equations of the standard string sigma model.Comment: 26 pages, latex, v2 typos correcte

Soluble CD200 Correlates With Interleukin-6 Levels in Sera of COPD Patients: Potential Implication of the CD200/CD200R Axis in the Disease Course

BACKGROUND: COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD. METHODS: To address this, we analyzed the serum samples from COPD patients and normal controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical parameters. In addition, basic studies were conducted in CD200-deficient and wild-type mice in which COPD-like inflammation was induced with elastase/LPS followed by lung and serum component analysis. RESULTS: We observed a positive correlation between serum sCD200 and IL-6 levels as well as a trend toward a negative correlation of sCD200 with vitamin D3 in COPD patients. Further investigations in mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice, the early onset of COPD-like lung inflammation was similar in CD200-deficient and wild-type animals in terms of immune cell infiltration, emphysematous changes, and mucus overproduction. CONCLUSIONS: While our murine studies suggest that the co-inhibitory molecule CD200 does not appear to play a prominent role in the early onset of COPD-like features, correlation of sCD200 serum levels with COPD-related parameters in humans with established disease revealed that the CD200/CD200R axis may be mechanistically linked to the disease course in COPD patients

MTSS1 is a critical epigenetically regulated tumor suppressor in CML

Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1 overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI resistant CML stem cells in patients