Psychosocial/survivorship issues in breast cancer: are we doing better?

Modern breast cancer treatment offers many women greater prospects of cure or lengthier, good quality survival than was possible in the past. Advances include improved diagnostic and staging procedures, sophisticated onco-plastic surgery, enhanced radiotherapy techniques, and targeted systemic therapies. Much more attention has also been paid to cancer care delivery and access to specialist nurses, counsellors, support groups, and services provided by breast cancer charities. However, there are some concerns that these considerable improvements in treatment delivery and clinical outcomes have not led to similar benefits in the psychosocial, functional, and sexual well-being of women. The impact that non-life threatening, long-term iatrogenic harms of otherwise efficacious anticancer treatments has on patients is often overlooked; this is in part because of the emphasis given to physician-reported safety data in trials and the general exclusion of patient-reported outcomes (PROs). A failure to utilise reliable PRO measures has meant that some problems are underreported, which consequently has hampered much-needed research into ameliorative interventions. Systematic monitoring of quality of life-threatening side effects would permit early implementation of effective interventions and enhance long-term survivorship. Some examples of the pervasive difficulties that continue to affect survivors and evidence that certain interventions might help are provided in this commentary

Mass-spin relation for quark anti-quark bound states in non-commutative Yang-Mills theory

We investigate the relationship between mass and spin of quark anti-quark bound state in non-commutative gauge theory with N=4 supersymmetry. In the large N and large 't Hooft coupling limit, these bound states correspond to rotating open strings ending on a D-brane embedded into the supergravity background dual of the non-commutative field theory. Although the physical configuration of the open strings are drastically deformed by the non-commutativity, we find that the relation between the energy and the angular momentum of the bound state is unaffected by the non-commutativity parameter. We also clarify the holographic interpretation of quark anti-quark potential in non-commutative gauge theories.Comment: 22 pages, 9 figures, v2: references added, note added. v3: Major revision. New material (section 4) added. Title and abstract edite

Guanylate cyclase C limits systemic dissemination of a murine enteric pathogen

BACKGROUND: Guanylate Cyclase C (GC-C) is an apically-oriented transmembrane receptor that is expressed on epithelial cells of the intestine. Activation of GC-C by the endogenous ligands guanylin or uroguanylin elevates intracellular cGMP and is implicated in intestinal ion secretion, cell proliferation, apoptosis, intestinal barrier function, as well as the susceptibility of the intestine to inflammation. Our aim was to determine if GC-C is required for host defense during infection by the murine enteric pathogen Citrobacter rodentium of the family Enterobacteriacea. METHODS: GC-C(+/+) control mice or those having GC-C genetically ablated (GC-C(−/−)) were administered C. rodentium by orogastric gavage and analyzed at multiple time points up to post-infection day 20. Commensal bacteria were characterized in uninfected GC-C(+/+) and GC-C(−/−) mice using 16S rRNA PCR analysis. RESULTS: GC-C(−/−) mice had an increase in C. rodentium bacterial load in stool relative to GC-C(+/+). C. rodentium infection strongly decreased guanylin expression in GC-C(+/+) mice and, to an even greater degree, in GC-C(−/−) animals. Fluorescent tracer studies indicated that mice lacking GC-C, unlike GC-C(+/+) animals, had a substantial loss of intestinal barrier function early in the course of infection. Epithelial cell apoptosis was significantly increased in GC-C(−/−) mice following 10 days of infection and this was associated with increased frequency and numbers of C. rodentium translocation out of the intestine. Infection led to significant liver histopathology in GC-C(−/−) mice as well as lymphocyte infiltration and elevated cytokine and chemokine expression. Relative to naïve GC-C(+/+) mice, the commensal microflora load in uninfected GC-C(−/−) mice was decreased and bacterial composition was imbalanced and included outgrowth of the Enterobacteriacea family. CONCLUSIONS: This work demonstrates the novel finding that GC-C signaling is an essential component of host defense during murine enteric infection by reducing bacterial load and preventing systemic dissemination of attaching/effacing-lesion forming bacterial pathogens such as C. rodentium

Two-pathogen model with competition on clustered networks

Networks provide a mathematically rich framework to represent social contacts sufficient for the transmission of disease. Social networks are often highly clustered and fail to be locally tree-like. In this paper, we study the effects of clustering on the spread of sequential strains of a pathogen using the generating function formulation under a complete cross-immunity coupling, deriving conditions for the threshold of coexistence of the second strain. We show that clustering reduces the coexistence threshold of the second strain and its outbreak size in Poisson networks, whilst exhibiting the opposite effects on uniform-degree models. We conclude that clustering within a population must increase the ability of the second wave of an epidemic to spread over a network. We apply our model to the study of multilayer clustered networks and observe the fracturing of the residual graph at two distinct transmissibilities.Publisher PDFPeer reviewe