995 research outputs found

    Multilayer metamaterial absorbers inspired by perfectly matched layers

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    We derive periodic multilayer absorbers with effective uniaxial properties similar to perfectly matched layers (PML). This approximate representation of PML is based on the effective medium theory and we call it an effective medium PML (EM-PML). We compare the spatial reflection spectrum of the layered absorbers to that of a PML material and demonstrate that after neglecting gain and magnetic properties, the absorber remains functional. This opens a route to create electromagnetic absorbers for real and not only numerical applications and as an example we introduce a layered absorber for the wavelength of 88~μ\mum made of SiO2_2 and NaCl. We also show that similar cylindrical core-shell nanostructures derived from flat multilayers also exhibit very good absorptive and reflective properties despite the different geometry

    Timing of immune escape linked to success or failure of vaccination

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    Successful vaccination against HIV should limit viral replication sufficiently to prevent the emergence of viral immune escape mutations. Broadly directed immunity is likely to be required to limit opportunities for immune escape variants to flourish. We studied the emergence of an SIV Gag cytotoxic T cell immune escape variant in pigtail macaques expressing the Mane-A*10 MHC I allele using a quantitative RT-PCR to measure viral loads of escape and wild type variants. Animals receiving whole Gag expressing vaccines completely controlled an SIVmac251 challenge, had broader CTL responses and exhibited minimal CTL escape. In contrast, animals vaccinated with only a single CTL epitope and challenged with the same SIVmac251 stock had high levels of viral replication and rapid CTL escape. Unvaccinated na&iuml;ve animals exhibited a slower emergence of immune escape variants. Thus narrowly directed vaccination against a single epitope resulted in rapid immune escape and viral levels equivalent to that of na&iuml;ve unvaccinated animals. These results emphasize the importance of inducing broadly directed HIV-specific immunity that effectively quashes early viral replication and limits the generation of immune escape variants. This has important implications for the selection of HIV vaccines for expanded human trials.<br /

    Traditional electrosurgery and a low thermal injury dissection device yield different outcomes following bilateral skin-sparing mastectomy: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Although a skin- and nipple-sparing mastectomy technique offers distinct cosmetic and reconstructive advantages over traditional methods, partial skin flap and nipple necrosis remain a significant source of post-operative morbidity. Prior work has suggested that collateral thermal damage resulting from electrocautery use during skin flap development is a potential source of this complication. This report describes the case of a smoker with recurrent ductal carcinoma <it>in situ </it>(DCIS) who experienced significant unilateral skin necrosis following bilateral skin-sparing mastectomy while participating in a clinical trial examining mastectomy outcomes with two different surgical devices. This unexpected complication has implications for the choice of dissection devices in procedures requiring skin flap preservation.</p> <p>Case presentation</p> <p>The patient was a 61-year-old Caucasian woman who was a smoker with recurrent DCIS of her right breast. As part of the clinical trial, each breast was randomized to either the standard of care treatment group (a scalpel and a traditional electrosurgical device) or treatment with a novel, low thermal injury dissection device, allowing for a direct, internally controlled comparison of surgical outcomes. Post-operative follow-up at six days was unremarkable for both operative sites. At 16 days post-surgery, the patient presented with a significant wound necrosis in the mastectomy site randomized to the control study group. Following debridement and closure, this site progressively healed over 10 weeks. The contralateral mastectomy, randomized to the alternative device, healed normally.</p> <p>Conclusion</p> <p>We hypothesize that thermal damage to the subcutaneous microvasculature during flap dissection may have contributed to this complication and that the use of a low thermal injury dissection device may be advantageous in select patients undergoing skin- and nipple-sparing mastectomy.</p

    Natural Killer Cell Mediated Cytotoxic Responses in the Tasmanian Devil

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    The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against DFTD cells and foreign tumour cells. The two Tasmanian devils immunised with irradiated DFTD cells did not form cytotoxic or humoral responses against DFTD cells, even after multiple immunisations. However, following immunisation with xenogenic K562 cells, devils did produce cytotoxic responses and antibodies against this foreign tumour cell line. The cytotoxicity appeared to occur through the activity of natural killer (NK) cells in an antibody dependent manner. Classical NK cell responses, such as innate killing of DFTD and foreign cancer cells, were not observed. Cells with an NK-like phenotype comprised approximately 4 percent of peripheral blood mononuclear cells. The results of this study suggest that Tasmanian devils have NK cells with functional cytotoxic pathways. Although devil NK cells do not directly recognise DFTD cancer cells, the development of antibody dependent cell-mediated cytotoxicity presents a potential pathway to induce cytotoxic responses against the disease. These findings have positive implications for future DFTD vaccine research

    Identification of an INa-dependent and Ito-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient

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    Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS

    The effect of clinician-patient alliance and communication on treatment adherence in mental health care: a systematic review

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    Background Nonadherence to mental health treatment incurs clinical and economic burdens. The clinician-patient alliance, negotiated through clinical interaction, presents a critical intervention point. Recent medical reviews of communication and adherence behaviour exclude studies with psychiatric samples. The following examines the impact of clinician-patient alliance and communication on adherence in mental health, identifying the specific mechanisms that mobilise patient engagement. Methods In December 2010, a systematic search was conducted in Pubmed, PsychInfo, Web of Science, Cochrane Library, Embase and Cinahl and yielded 6672 titles. A secondary hand search was performed in relevant journals, grey literature and reference. Results 23 studies met the inclusion criteria for the review. The methodological quality overall was moderate. 17 studies reported positive associations with adherence, only four of which employed intervention designs. 10 studies examined the association between clinician-patient alliance and adherence. Subjective ratings of clinical communication styles and messages were assessed in 12 studies. 1 study examined the association between objectively rated communication and adherence. Meta-analysis was not possible due to heterogeneity of methods. Findings were presented as a narrative synthesis. Conclusions Clinician-patient alliance and communication are associated with more favourable patient adherence. Further research of observer rated communication would better facilitate the application of findings in clinical practice. Establishing agreement on the tasks of treatment, utilising collaborative styles of communication and discussion of treatment specifics may be important for clinicians in promoting cooperation with regimens. These findings align with those in health communication. However, the benefits of shared decision making for adherence in mental health are less conclusive than in general medicine

    Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study

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    <p>Abstract</p> <p>Objectives </p> <p>We have analyzed t(12;21)(p13:q22) in an attempt to evaluate the frequency and prognostic significance of <it>TEL-AML1 </it>fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH). Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD).</p> <p>Methods</p> <p>All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH) for t(12;21) in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD). We determined the prognostic significance of <it>TEL-AML1 </it>fusion represented by disease course and survival.</p> <p>Results</p> <p><it>TEL-AML1 </it>fusion gene was positive in (37.5%) in newly diagnosed patients. There was a significant correlation between <it>TEL-AML1 </it>fusion gene both at diagnosis (r = 0.5, P = 0.003) and as a MRD (r = 0.4, P = 0.01) with favorable course. Kaplan-Meier curve for the presence of <it>TEL-AML1 </it>fusion at the diagnosis was associated with a better probability of overall survival (OS); mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006). Also, the persistence at <it>TEL-AML1 </it>fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of <it>TEL-AML1 </it>fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS.</p> <p>Conclusion</p> <p>For most patients, the presence of <it>TEL-AML1 </it>fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of <it>TEL-AML1 </it>fusion as MRD has no additive prognostic value.</p

    Study of Bc+B_c^+ decays to the K+Kπ+K^+K^-\pi^+ final state and evidence for the decay Bc+χc0π+B_c^+\to\chi_{c0}\pi^+

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    A study of Bc+K+Kπ+B_c^+\to K^+K^-\pi^+ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 fb1\mathrm{fb}^{-1} collected by the LHCb experiment in pppp collisions at centre-of-mass energies of 77 and 88 TeV. Evidence for the decay Bc+χc0(K+K)π+B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+ is reported with a significance of 4.0 standard deviations, resulting in the measurement of σ(Bc+)σ(B+)×B(Bc+χc0π+)\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+) to be (9.83.0+3.4(stat)±0.8(syst))×106(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}. Here B\mathcal{B} denotes a branching fraction while σ(Bc+)\sigma(B_c^+) and σ(B+)\sigma(B^+) are the production cross-sections for Bc+B_c^+ and B+B^+ mesons. An indication of bˉc\bar b c weak annihilation is found for the region m(Kπ+)<1.834GeV ⁣/c2m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference
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