Should young age be a contra-indication to breast conservation treatment in Chinese women? Twelve-year experience from a public cancer centre in Hong Kong

Objective: It has been proposed that young women should not be treated by breast conservation treatment because of a higher risk of local recurrences and worse survival. We therefore examined whether breast conservation treatment in young Chinese women yielded inferior clinical outcomes compared to modified radical mastectomy. Design: Retrospective study. Setting: Clinical oncology department in a public hospital in Hong Kong. Patients: A total of 258 Chinese women with invasive breast cancer, aged below 40 years, and referred between January 1994 and July 2006. Results: A total of 124 (48%) and 134 (52%) patients were treated by breast conservation treatment and modified radical mastectomy, respectively. Mastectomy patients tended to have larger primary tumours (P<0.001) and more nodal involvement (P<0.001). At a median follow-up of 6.5 years, there was no significant difference in the local failure-free survival rate (92% vs 93%, P=0.324) and loco-regional failure-free survival rate (89% vs 88%, P=0.721) in patients having breast conservation treatment and mastectomy. Probably due to their earlier presentation with disease, the former actually had better 6-year distant failure-free survival (88% vs 71%, P=0.002) and overall survival (92% vs 81%, P=0.173) rates. Multivariate analyses showed that both the resection margin status (hazard ratio=2.77, P=0.050) and the presence of peritumoural vascular invasion (hazard ratio=3.01, P=0.038) were independent predictors of local recurrence; the nodal status (hazard ratio=3.91, P<0.001) was the only predictive factor for overall survival. The choice of breast conservation treatment (vs modified radical mastectomy) had no apparent adverse impact on all the clinical outcome parameters analysed. Conclusion: Breast conservation treatment is a reasonable option for many suitably selected young Chinese women.published_or_final_versio

Collider and Dark Matter Phenomenology of Models with Mirage Unification

We examine supersymmetric models with mixed modulus-anomaly mediated SUSY breaking (MM-AMSB) soft terms which get comparable contributions to SUSY breaking from moduli-mediation and anomaly-mediation. The apparent (mirage) unification of soft SUSY breaking terms at Q=mu_mir not associated with any physical threshold is the hallmark of this scenario. The MM-AMSB structure of soft terms arises in models of string compactification with fluxes, where the addition of an anti-brane leads to an uplifting potential and a de Sitter universe, as first constructed by Kachru {\it et al.}. The phenomenology mainly depends on the relative strength of moduli- and anomaly-mediated SUSY breaking contributions, and on the Higgs and matter field modular weights, which are determined by the location of these fields in the extra dimensions. We delineate the allowed parameter space for a low and high value of tan(beta), for a wide range of modular weight choices. We calculate the neutralino relic density and display the WMAP-allowed regions. We show the reach of the CERN LHC and of the International Linear Collider. We discuss aspects of MM-AMSB models for Tevatron, LHC and ILC searches, muon g-2 and b->s \gamma branching fraction. We also calculate direct and indirect dark matter detection rates, and show that almost all WMAP-allowed models should be accessible to a ton-scale noble gas detector. Finally, we comment on the potential of colliders to measure the mirage unification scale and modular weights in the difficult case where mu_mir>>M_GUT.Comment: 34 pages plus 42 EPS figures; version with high resolution figures is at http://www.hep.fsu.edu/~bae

Collider and Dark Matter Searches in Models with Mixed Modulus-Anomaly Mediated SUSY Breaking

We investigate the phenomenology of supersymmetric models where moduli fields and the Weyl anomaly make comparable contributions to SUSY breaking effects in the observable sector of fields. This mixed modulus-anomaly mediated supersymmetry breaking (MM-AMSB) scenario is inspired by models of string compactification with fluxes, which have been shown to yield a de Sitter vacuum (as in the recent construction by Kachru {\it et al}). The phenomenology depends on the so-called modular weights which, in turn, depend on the location of various fields in the extra dimensions. We find that the model with zero modular weights gives mass spectra characterized by very light top squarks and/or tau sleptons, or where M_1\sim -M_2 so that the bino and wino are approximately degenerate. The top squark mass can be in the range required by successful electroweak baryogenesis. The measured relic density of cold dark matter can be obtained via top squark co-annihilation at low \tan\beta, tau slepton co-annihilation at large \tan\beta or via bino-wino coannihilation. Then, we typically find low rates for direct and indirect detection of neutralino dark matter. However, essentially all the WMAP-allowed parameter space can be probed by experiments at the CERN LHC, while significant portions may also be explored at an e^+e^- collider with \sqrt{s}=0.5--1 TeV. We also investigate a case with non-zero modular weights. In this case, co-annihilation, A-funnel annihilation and bulk annihilation of neutralinos are all allowed. Results for future colliders are qualitatively similar, but prospects for indirect dark matter searches via gamma rays and anti-particles are somewhat better.Comment: 38 pages including 22 EPS figures; latest version posted to conform with published versio

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

The electrophotonic silicon biosensor

The emergence of personalized and stratified medicine requires label-free and low-cost diagnostic technology capable of monitoring multiple disease biomarkers in parallel. Silicon photonic biosensors combine high sensitivity analysis with scalable, low-cost manufacturing technology but they tend to measure only a single biomarker and provide no information about their (bio)chemical activity. Here, we introduce an electrochemical silicon photonic sensor capable of highly sensitive and multiparameter profiling of biomolecules. Our electro-photonic technology consists of microring resonators optimally n-doped to support high Q resonances alongside electrochemical processes in situ. The inclusion of electrochemical processes enables site selective immobilization of different biomolecules, here single stranded DNA, onto individual microrings within a sensor array. The combination of photonic and electrochemical characterization of molecules bound to the sensor surface also provides direct quantification of binding density and unique insight into chemical reactivity that is unavailable with photonic detection alone. By exploiting both the photonic and the electrical properties of silicon, the sensor opens new modalities for sensing on the micro-scale

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

Techno-economic assessment of fertiliser drawn forward osmosis process for greenwall plants from urban wastewater

© 2019 Institution of Chemical Engineers Pressure-assisted osmosis (PAO) has been suggested to integrate with fertiliser driven forward osmosis (FDFO) to improve the overall efficiency of simultaneous wastewater reuse and fertiliser osmotic dilution. This study aims to demonstrate the techno-economic feasibility of pressure-assisted fertiliser driven forward osmosis (PAFDO) hybrid system compared to the existing ultraviolet and reverse osmosis (UV–RO) process. The results showed that coupling FDFO with PAO (i.e. PAFDO) could help fulfill the water quality required for greenwall fertigation. An economic analysis on capital and operational costs for the PAFDO showed that the PAO mode application at a lower FDFO dilution stage could significantly reduce the costs. However, when considering the different applied pressures in PAO (i.e. 2, 4, and 6 bar), the increase in the total water cost was not significant. This indicates that the dilution stage for applying PAO is more sensitive to the total water cost of the PAFDO than the applied pressure. A coupling of higher average water flux (>10 L/m2h) and lower draw solution (DS) dilution factor (DF < 60) is recommended. Therefore, this could make the PAFDO system economically viable compared to the benchmark for the UV-RO disinfection system