Standard wide local excision or bilateral reduction mammoplasty in large-breasted women with small tumours: Surgical and patient-reported outcomes.

Introduction Oncoplastic breast surgery is used to extend the role of breast-conserving surgery (BCS) to women with an unfavourable tumour to breast volume ratio. However, large-breasted women with a relatively small breast cancer may be offered bilateral reduction mammoplasty (BRM) despite being suitable for standard BCS as the more complex surgery may have advantages in terms of patient satisfaction and reduced adverse effects of radiotherapy.Patient and methods This retrospective study evaluated surgical and patient-reported outcome measures (PROMs) in large-breasted women with early ( 0.05).Conclusion Limitations of this study mean it can only be regarded as hypothesis-generating. Nonetheless, the trends merit a prospective study to investigate the optimal management of smaller breast cancers in larger-breasted women

Bilateral mammoplasty for cancer: Surgical, oncological and patient-reported outcomes.

Introduction Bilateral mammoplasty (BM) can optimise oncological safety and aesthetic outcomes in women with large or ptotic breasts whose tumour to breast volume ratio or tumour location pose a challenge to standard breast-conserving therapy (BCT) and for whom mastectomy (with or without reconstruction) may be the only alternative.Methods We undertook a comprehensive analysis of surgical outcomes (complications according to the Clavien Dindo classification), acute radiation morbidity (Radiation Therapy Oncology Group classification), oncological outcomes, and patient satisfaction (BREAST-Q questionnaire) in women who underwent BM for breast cancer (BC) from June 2009-November 2014.Results 168 women were included. Median age was 55 years (range:33-84) and median tumour size at imaging 35 mm (range:0-170). Median specimen weight was 242 g (range 39-1824). The wise pattern technique was used in 87.5% of procedures. At least one complication occurred in 68 (40.5%) women, mostly Clavien Dindo grade 1. Grade 3 complications were infrequent (8.9%) but occurred mainly on the therapeutic mammoplasty (TM) side (p < 0.05). Complications were associated with higher BMI, specimen weight and longer time to radiotherapy (p < 0.05). Median follow-up was 37 months (range: 13-77). Local recurrence occurred in 3 (1.8%), distant metastases in 5 (3.0%), and 10 (6.0%) women have died. The median score for 'satisfaction with breasts' was 77 (range: 0-100).Conclusions This study provides concurrent data on surgical, oncological and patient-reported outcomes. It offers evidence that BM is an effective treatment for breast cancer in large- or ptotic-breasted women

The discourse of Olympic security 2012 : London 2012

This paper uses a combination of CDA and CL to investigate the discursive realization of the security operation for the 2012 London Olympic Games. Drawing on Didier Bigo’s (2008) conceptualisation of the ‘banopticon’, it address two questions: what distinctive linguistic features are used in documents relating to security for London 2012; and, how is Olympic security realized as a discursive practice in these documents? Findings suggest that the documents indeed realized key banoptic features of the banopticon: exceptionalism, exclusion and prediction, as well as what we call ‘pedagogisation’. Claims were made for the exceptional scale of the Olympic events; predictive technologies were proposed to assess the threat from terrorism; and documentary evidence suggests that access to Olympic venues was being constituted to resemble transit through national boundarie

Initial experience of the BREAST-Q breast-conserving therapy module.

Purpose The most recently developed module of the BREAST-Q, a validated patient outcome measure, is for patients who have undergone breast-conserving therapy (BCT) for cancer. This aim of this study was to assess patient satisfaction and quality of life after BCT using BREAST-Q, investigate clinical risk factors for lower satisfaction and explore the relationship between patient satisfaction with the appearance of their breasts and the other domains of the BREAST-Q.Methods Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate at the time of their annual surveillance mammogram. Clinicopathological data were collected from an electronic database. Linear regression was used to evaluate risk factors for lower satisfaction. Spearman's rho correlation coefficients were calculated to evaluate the relationship between domains.Results 200 women completed the questionnaire. Mean age was 60 years (SD 11.1). Time from surgery was 35.5 months (SD 17.8). Median score for 'Satisfaction with breasts' was 68 (interquartile range 55-80). Lowest scores were for 'sexual wellbeing' (57, IQR 45-66). On multivariate analysis, BMI at the time of surgery (p = 0.002), delayed wound healing (p = 0.001) and axillary surgery (p = 0.003) were independent risk factors for lower satisfaction. There was significant correlation between 'Satisfaction with breasts' and all other BREAST-Q domains.Conclusion High BMI, delayed wound healing and axillary surgery are risk factors for lower patient satisfaction. This first publication reporting the whole dataset for the BREAST-Q BCT will serve as a benchmark for future studies of patient satisfaction following BCT

The impact of predation by marine mammals on Patagonian toothfish longline fisheries

Predatory interaction of marine mammals with longline fisheries is observed globally, leading to partial or complete loss of the catch and in some parts of the world to considerable financial loss. Depredation can also create additional unrecorded fishing mortality of a stock and has the potential to introduce bias to stock assessments. Here we aim to characterise depredation in the Patagonian toothfish (Dissostichus eleginoides) fishery around South Georgia focusing on the spatio-temporal component of these interactions. Antarctic fur seals (Arctocephalus gazella), sperm whales (Physeter macrocephalus), and orcas (Orcinus orca) frequently feed on fish hooked on longlines around South Georgia. A third of longlines encounter sperm whales, but loss of catch due to sperm whales is insignificant when compared to that due to orcas, which interact with only 5% of longlines but can take more than half of the catch in some cases. Orca depredation around South Georgia is spatially limited and focused in areas of putative migration routes, and the impact is compounded as a result of the fishery also concentrating in those areas at those times. Understanding the seasonal behaviour of orcas and the spatial and temporal distribution of “depredation hot spots” can reduce marine mammal interactions, will improve assessment and management of the stock and contribute to increased operational efficiency of the fishery. Such information is valuable in the effort to resolve the human-mammal conflict for resources

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

The potential role of three-dimensional surface imaging as a tool to evaluate aesthetic outcome after Breast Conserving Therapy (BCT).

Purpose To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT).Methods Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate. Participants completed a satisfaction questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were measured on the images. Assessment of aesthetic outcome was undertaken by a panel of clinicians. The Kruskal-Wallis test was used to assess the relationship between volume and shape symmetry measurements with the panel score. Spearman's rho correlations were used to assess the relationship between the measurements and patient satisfaction.Results 200 women participated. Median volume symmetry was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants were grouped according to panel assessment of aesthetic outcome (poor, fair, good, excellent) and the median volume and shape symmetry was calculated for each group. Volume symmetry significantly differed between the groups. Post hoc pairwise comparisons demonstrated that these differences existed between panel scores of fair versus good and good versus excellent. Median shape symmetry also differed according to patient panel groups with four significant pairwise comparisons between poor versus good, poor versus excellent, fair versus good and fair versus excellent. There was a significant but weak correlation of both volume symmetry and surface asymmetry with BREAST-Q scores (correlation coefficients 0.187 and -0.229, respectively).Conclusion Breast volume and shape symmetry are both associated with panel assessment scores and patient satisfaction. The objective volume and shape symmetry measures were strongly associated with panel assessment scores, such that a 3D-SI tool could replace panel assessment as a faster and more objective method of evaluating aesthetic outcomes

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

Entry of the bat influenza H17N10 virus into mammalian cells is enabled by the MHC class II HLA-DR receptor

Haemagglutinin and neuraminidase surface glycoproteins of the bat influenza H17N10 virus neither bind to nor cleave sialic acid receptors, indicating that this virus employs cell entry mechanisms distinct from those of classical influenza A viruses. We observed that certain human haematopoietic cancer cell lines and canine MDCK II cells are susceptible to H17-pseudotyped viruses. We identified the human HLA-DR receptor as an entry mediator for H17 pseudotypes, suggesting that H17N10 possesses zoonotic potential

N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models