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    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

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    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

    Insights into the composition of recalcitrant organic matter from estuarine sediments using NMR spectroscopy

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    peer-reviewedThe full text of this article will not be available on ULIR until the embargo expires on the 24/05/2018Sediment cores (ca. 6 m) from an estuarine environment gave insights into the composition and preservation of recalcitrant organic carbon (OC) in the environment. The coring locations provided organic matter (OM) of terrestrial origin and of marine origin. Our study specifically focused on the humin (HU), the OM fraction that is most difficult to isolate and to characterize. HU fractions were compared with the total OM recovered after removal of the associated mineral colloids. Solid state and multiphase (nuclear magnetic resonance) NMR experiments were carried out on dried and swollen samples to obtain comparative information about the whole samples and the fractionated samples. The total OM associated with the clay-size fraction provided a standard that allowed differences between the fractions to be observed. The NMR data provided new insights into the molecular structures that become part of the long term C sink in sediments. The recalcitrant OC in the sediments is composed mainly of aliphatic hydrocarbon material that may be protected from, or otherwise unavailable for, degradation. Microbial peptides and carbohydrates were also shown to be important contributors to the C sink and these biomolecules may be from living biomass or preserved necromass. Lignin residues formed only a small part of the OM in the surface sediments but made a greater contribution at depth. Highly ordered components in HU (that resists swelling by dimethylsulfoxide, DMSO) play a major role in C sequestration

    Assessment of 1991 NEHRP Provisions for Nonstructural Components and Recommended Revisions

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    As one part of the 1994 update effort of the 1991 NEHRP provisions, the seismic design force formulas for nonstructural components as they exist in the 1991 provisions are critically assessed and some of their shortcomings are identified. Various levels of improvements to these formulas are then presented which, on the one hand, preserve the equivalent lateral force format for design applicability and, on the other, correct some of the deficiencies on the basis of analyses, experimental results and observation data from past earthquakes. Based on different interpretations of the component seismic coefficients as well as different degrees of simplicity required in practical design, three recommendations are proposed. The first recommended revision is the most comprehensive in that both effects of nonstructural component anchorage detailing and its supporting structural characteristics are taken into account. The second recommendation is a structure-driven type of modification of the current provisions and is motivated by the possibility that nonstructural component information during a design process is not available. The third revision, however, mainly concentrates on the effect of nonstructural component characteristics on the design force although it partially implies structural effects in the process of determining the response modification coefficient. The maximum and minimum design forces in the three recommendations are compared with those produced by the 1991 NEHRP provisions, the 1991 UBC, and the 1985 Tri-Service codes. Case studies of a parapet, a storage rack and a general equipment attached to a reinforced concrete shear wall structure are provided to show the relative conservatism involved in different codes and the importance of the factors ignored in the current provisions. Simple displacement equations are also developed in this report to provide deformation information needed in some cases of practical design

    HER2 overexpression of breast cancers in Hong Kong: Prevalence and concordance between immunohistochemistry and in-situ hybridisation assays

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    Objectives: To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. Design: Retrospective study. Setting: Department of Clinical Oncology in a public hospital in Hong Kong. Patients: All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). Results: There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. Conclusions: More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.published_or_final_versio

    Macroscopic transport by synthetic molecular machines

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    Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with—and perform physical tasks in—the macroscopic world represents a significant hurdle for molecular nanotechnology. Here we describe a wholly synthetic molecular system that converts an external energy source (light) into biased brownian motion to transport a macroscopic cargo and do measurable work. The millimetre-scale directional transport of a liquid on a surface is achieved by using the biased brownian motion of stimuli-responsive rotaxanes (‘molecular shuttles’) to expose or conceal fluoroalkane residues and thereby modify surface tension. The collective operation of a monolayer of the molecular shuttles is sufficient to power the movement of a microlitre droplet of diiodomethane up a twelve-degree incline.

    Increased Efficiency of the Artificial Bee Colony Algorithm Using the Pheromone Technique

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    Artificial Bee Colony (ABC) is a powerful metaheuristic algorithm inspired by the behavior of a honey bee swarm. ABC suffers from poor exploitation and, in some cases, poor exploration. Ant Colony Optimization (ACO) is another metaheuristic algorithm that uses pheromones as a guide for an ant to find its way. This study used a pheromone technique from ACO on ABC to enhance its exploration and exploitation. The performance of the proposed method was verified through twenty instances from TSPLIB. The results were compared with the original ABC method and showed that the proposed method leverages the performance of ABC

    Prosthetic stent graft infection after endovascular abdominal aortic aneurysm repair

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    ObjectiveThe purpose of this report is to discuss the incidence, diagnosis, and management of stent graft infections after endovascular aneurysm repair (EVAR).MethodsData were collected from the hospital database and medical case notes for all patients with infected endografts after elective or emergency EVAR for abdominal aortic aneurysm (AAA) during the last 8 years in two university teaching hospitals in Northern Ireland. The data included the patient’s age, gender, presentation of sepsis, treatment offered, and the ultimate outcome. The diagnosis of graft-related sepsis was established by a combination of investigations including inflammatory markers, labelled white cell scan, computed tomography (CT) scan, microbiology cultures, and postmortem examination.ResultsGraft-related septic complications occurred in six of 509 patients, including 433 elective repairs and 76 emergency endografts for ruptured AAA. Two patients presented with left psoas abscess and were treated successfully with extra-anatomic bypass and removal of the infected stent graft. Two more patients presented with infected graft without other evidence of intra-abdominal sepsis: one underwent successful removal of the infected prosthesis with extra-anatomical bypass, and the other was treated conservatively and died of progressively worsening sepsis. The fifth patient presented with unexplained fever and died suddenly, with a postmortem diagnosis of aortoenteric fistula and ruptured aneurysm. The last patient presented with an aortoenteric fistula, was treated conservatively in view of concurrent myelodysplasia, and died of possible aneurysm rupture.ConclusionThis report emphasizes the need for continued awareness of potential graft-related septic complications in patients undergoing EVAR of AAA. Attention to detail with regard to sterility and antibiotic prophylaxis during stent grafting and during any secondary interventions is vital in reducing the risk of infection. In addition, early recognition and prompt treatment are essential for a successful outcome

    Protective Immunity and Immunopathology in Ehrlichiosis

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    Human monocytic ehrlichiosis, a tick transmitted infection, ranges in severity from apparently subclinical to fatal toxic shock-like disease. Models in immunocompetent mice range from abortive to uniformly lethal infection, depending on the Ehrlichia species, inoculum dose, and inoculation route. Effective immunity is mediated by CD4 + T lymphocytes and gamma interferon. Lethal infection occurs with early overproduction of proinflammatory cytokines and overproduction of TNF alpha and IL-10 by CD8 + T lymphocytes. Furthermore, fatal ehrlichiosis is associated with TLR 9/MyD88 signaling, upregulation of several inflammasome complexes, and secretion of IL-1 beta, IL-1 alpha, and IL-18 by hepatic mononuclear cells, thus suggesting activation of canonical and noncanonical inflammasome pathways, a deleterious role of IL-18, and a protective role of caspase 1. Autophagy promotes ehrlichial infection, whereas MyD88 signaling hinders ehrlichial infection by inhibiting autophagy induction and flux. During infection of hepatocytes by the lethal ehrlichial species, after interferon alpha receptor signaling, the activation of caspase 11 results in the production of inflammasome-dependent IL-1 beta, extracellular secretion of HMGB1, and pyroptosis. HMGB1 has high levels in lethal ehrlichiosis, thereby suggesting a role in toxic shock. Studies of primary bone marrow-derived macrophages infected by highly avirulent or mildly avirulent ehrlichiae have revealed divergent M1 and M2 macrophage polarization associated with the generation of pathogenic CD8 T cells and neutrophils, and excessive inflammation, or with strong expansion of protective Th1 and NKT cells, resolution of inflammation, and clearance of infection, respectively
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