2,281 research outputs found

    Canada and the Battle of Vimy Ridge

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    Public history posters on Canada’s military past about the April 9 - 12, 1917 battle of Vimy Ridge by the Canadian Corps, by students Barry Ho, Maxwell Blair, Elena Melania Panescu, and Patrick Jedrzejkohttps://source.sheridancollege.ca/swfhass_military_posters/1003/thumbnail.jp

    The Significance of C-Met in Different Molecular Sub-Types of Invasive Breast Cancer.

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    PhDIntroduction: Basal-like (BL) breast cancer is an aggressive sub-type of breast cancer for which there is no targeted systemic therapy. C-Met is a receptor tyrosine kinase implicated in breast cancer. Clinical trials assessing the efficacy of anti-c-Met therapy are underway, yet few studies have analysed the clinical significance of c-Met expression and/or activation in breast cancer, in particular whether there is a correlation with molecular sub-type. The aims of this study are: 1) to establish the clinical significance of c-Met expression in invasive breast cancer, 2) evaluate the novel proximity ligation assay (PLA) as a method of measuring c-Met activation and 3) address the effect of hepatocyte growth factor (HGF)-mediated c-Met phosphorylation on migration and protein expression in cell lines representative of the BL sub-type. Methods: Immunohistochemistry for c-Met was performed on 1455 cases of breast cancer using tissue microarray (TMA) technology. The PLA was performed on TMAs constructed from 181 breast cancers. C-Met expression and the PLA product were correlated with clinico-pathological parameters and survival. The effects of HGF on cell migration and protein expression were assessed using migration assays, western blots and immunofluorescent studies. Results: C-Met expression was independently associated with BL breast cancer (odds ratio = 6.44, 95% confidence interval (CI) = 1.74-23.78, p = 0.005) and reduced overall survival (hazard ratio = 1.81, 95% CI = 1.07-3.06), p = 0.026). The PLA signal was not associated with molecular sub-type or survival. HGF stimulation was associated with a significant increase in BL cell migration (p < 0.01) but no evidence of epithelial-mesenchymal transition was observed. Conclusion: My findings suggest BL breast cancer patients should be included in future trials of anti-c-Met therapy. Further work is necessary to establish the prognostic utility of the PLA as a measure of c-Met activation and the mechanisms driving HGF-mediated cell migration.Cancer Research U

    The Effect of Race, Sex, and Insurance Status on Time-to-Listing Decisions for Liver Transplantation

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    Fair allocation of organs to candidates listed for transplantation is fundamental to organ-donation policies. Processes leading to listing decisions are neither regulated nor understood. We explored whether patient characteristics affected timeliness of listing using population-based data on 144,507 adults hospitalized with liver-related disease in Pennsylvania. We linked hospitalizations to other secondary data and found 3,071 listed for transplants, 1,537 received transplants, and 57,020 died. Among candidates, 61% (n = 1,879) and 85.5% (n = 2,626) were listed within 1 and 3 years of diagnosis; 26.7% (n = 1,130) and 95% (n = 1,468) of recipients were transplanted within 1 and 3 years of listing. Using competing-risks models, we found few overall differences by sex, but both black patients and those insured by Medicare and Medicaid (combined) waited longer before being listed. Patients with combined Medicare and Medicaid insurance, as well as those with Medicaid alone, were also more likely to die without ever being listed. Once listed, the time to transplant was slightly longer for women, but it did not differ by race/ethnicity or insurance. The early time period from diagnosis to listing for liver transplantation reveals unwanted variation related to demographics that jeopardizes overall fairness of organ allocation and needs to be further explored

    Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature.</p> <p>Case presentation</p> <p>A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity.</p> <p>Conclusion</p> <p>We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity.</p

    Engineered swift equilibration of a Brownian particle

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    A fundamental and intrinsic property of any device or natural system is its relaxation time relax, which is the time it takes to return to equilibrium after the sudden change of a control parameter [1]. Reducing tautau relax , is frequently necessary, and is often obtained by a complex feedback process. To overcome the limitations of such an approach, alternative methods based on driving have been recently demonstrated [2, 3], for isolated quantum and classical systems [4--9]. Their extension to open systems in contact with a thermostat is a stumbling block for applications. Here, we design a protocol,named Engineered Swift Equilibration (ESE), that shortcuts time-consuming relaxations, and we apply it to a Brownian particle trapped in an optical potential whose properties can be controlled in time. We implement the process experimentally, showing that it allows the system to reach equilibrium times faster than the natural equilibration rate. We also estimate the increase of the dissipated energy needed to get such a time reduction. The method paves the way for applications in micro and nano devices, where the reduction of operation time represents as substantial a challenge as miniaturization [10]. The concepts of equilibrium and of transformations from an equilibrium state to another, are cornerstones of thermodynamics. A textbook illustration is provided by the expansion of a gas, starting at equilibrium and expanding to reach a new equilibrium in a larger vessel. This operation can be performed either very slowly by a piston, without dissipating energy into the environment, or alternatively quickly, letting the piston freely move to reach the new volume

    The prepectoral, hybrid breast reconstruction : the synergy of lipofilling and breast implants

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    Background: Breast reconstruction modalities are based on autologous tissue transfer, implants, or a combination of both. The aim of an allogeneic breast reconstruction is to minimize the impact of the implant on surrounding tissues to achieve an aesthetically pleasing result. Accurate tissue coverage, proper implant selection, and implant location are the absolute concerns in planning an implant-based reconstruction. Methods: A single surgeon's experience with the ergonomic, hybrid approach in primary and secondary breast reconstructions is presented. The hybrid approach is based on tissue expansion followed by serial sessions of fat grafting to augment the residual autologous (subcutaneous) compartment. The last step included the insertion of a prepectoral, ergonomic implant to obtain central core projection and additional volume. Results: Fifty-six hybrid breast reconstructions were performed with a mean follow-up of 24.1 months. Aesthetic outcomes and patient satisfaction have been good with pleasing breast projection, natural breast motion, and optimal coverage of the prepectoral implants. Conclusions: The hybrid reconstructive approach is a reliable technique to improve the outcomes in implant-based breast reconstructions. The 2-step, prepectoral approach with expander-to-implant exchange allows better control of the final breast shape, and complications related to submuscular approaches are avoided. Fat grafting adds an autologous benefit to obtain natural results

    Expression of HSP70 and Its Relation with Other Cytokines in Human Middle Ear Effusion

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    ObjectivesWhile other cytokines are known to be associated with otitis media with effusion (OME), the involvement of heat shock protein 70 (HSP70) in middle ear effusion (MEE) is unknown. This study was undertaken to investigate the possibility of there being a HSP70 expression in human MEE and to determine its potential role as a cytokine in OME.MethodsThe levels of HSP70, tumor necrosis factor-alpha and interleukin-1beta were measured by enzyme-linked immunosorbent assay in the effusion of different groups of OME patient following collection of the MEE using our new collection system. The clinical characteristics of the OME patients and the MEE status were analyzed.ResultsHSP70 was expressed in all the types of MEE. The mucous and seromucous effusions showed higher HSP70 levels than that of the serous effusion. The HSP70 level was correlated with the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ÎČ in the effusions. The positive correlations between HSP70, TNF-α and IL-1ÎČ were statistically significant (P<0.05).ConclusionThe highly elevated level of HSP70 in the seromucous and mucous effusions implicates this protein in the chronicity of OME

    Integration of high‐risk human papillomavirus into cellular cancer‐related genes in head and neck cancer cell lines

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    BackgroundHuman papillomavirus (HPV)‐positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV‐positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16‐ and HPV18‐positive squamous cell carcinoma lines.MethodsE6/E7 alternate transcripts were assessed by reverse transcriptase‐polymerase chain reaction (RT‐PCR). Detection of integrated papillomavirus sequences (DIPS‐PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites.ResultsAll HPV‐positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer‐related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM‐SCC‐105 and UM‐GCC‐1 had only intergenic integration.ConclusionHPV integration into cancer‐related genes occurred in 7 of 9 HPV‐positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer‐related genes may be a secondary carcinogenic driver in HPV‐driven tumors. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840–852, 2017Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136719/1/hed24729_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136719/2/hed24729.pd
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