10 research outputs found

    Outbreak of H3N2 influenza at a US military base in Djibouti during the H1N1 pandemic of 2009.

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    PMC3855413BACKGROUND: Influenza pandemics have significant operational impact on deployed military personnel working in areas throughout the world. The US Department of Defense global influenza-like illness (ILI) surveillance network serves an important role in establishing baseline trends and can be leveraged to respond to outbreaks of respiratory illness. OBJECTIVE: We identified and characterized an operationally unique outbreak of H3N2 influenza at Camp Lemonnier, Djibouti occurring simultaneously with the H1N1 pandemic of 2009 [A(H1N1)pdm09]. METHODS: Enhanced surveillance for ILI was conducted at Camp Lemonnier in response to local reports of a possible outbreak during the A(H1N1)pdm09 pandemic. Samples were collected from consenting patients presenting with ILI (utilizing a modified case definition) and who completed a case report form. Samples were cultured and analyzed using standard real-time reverse transcriptase PCR (rt-RT-PCR) methodology and sequenced genetic material was phylogenetically compared to other published strains. RESULTS: rt-RT-PCR and DNA sequencing revealed that 25 (78%) of the 32 clinical samples collected were seasonal H3N2 and only 2 (6%) were A(H1N1)pdm09 influenza. The highest incidence of H3N2 occurred during the month of May and 80% of these were active duty military personnel. Phylogenetic analysis revealed that sequenced H3N2 strains were genetically similar to 2009 strains from the United States of America, Australia, and South east Asia. CONCLUSIONS: This outbreak highlights challenges in the investigation of influenza among deployed military populations and corroborates the public health importance of maintaining surveillance systems for ILI that can be enhanced locally when needed.JH Libraries Open Access Fun

    Coherence through Pitch

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    Recent musicological output has viewed neither the aesthetic concept of organicism nor the methodology of formalistic music analysis in a favourable light. Both organicism and formalistic music analysis in the current age have been plagued by criticisms concerning its validity, purpose, and function. Thus there has been a decrease in the perceived value and usefulness of both organicism as means of rendering contemporary post-tonal compositions as cohesive entities and music analysis as a means of elucidating such organic musical construction. My aims for my thesis are, at its simplest, two-fold. Drawing upon the aesthetics of organicism and cohesion as seen in Schoenberg’s writings, I aim primarily to espouse both the purpose and effectiveness of organicism as well as music analysis in rendering art music of the twentieth and twenty-first centuries comprehensible. I also argue that organicism must be accompanied by contrast in order to maintain musical variety and interest, and I explain how I, as a composer, satisfy these two imperatives in my own compositional output. A comprehensive motivic analysis of selected works from the twentieth century in conjunction with analyses of my own compositions created as part of this degree will not only demonstrate the presence of organicism but will also argue its value in achieving coherence in post-tonal music. Investigating the intervallic properties inherent in the primary musical material of each work will demonstrate the multifaceted ways in which the composer in question takes advantage of these properties to create a work that is simultaneously diverse yet unified in its structure. A consideration of the work’s construction on both the micro and macro scale (that is, the ways in which musical cells both interact and develop on local and global levels) will demonstrate how the composer has generated an organic structural trajectory through the manipulation of a small musical cell; it will also demonstrate how such an organic structure can create meaningful and coherent listenings of the work. I aim to convey the ways in which I and the selected composers develop material to achieve variety whilst maintaining unifying musical elements. I hope to convince the reader of the value of employing a motivic-based approach when composing post-tonal works due to its possibilities of ensuring musical coherence

    Phylogenetic analysis of H3N2 NA gene segments.

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    <p>*Phylogenetic tree of influenza A/H3N2 using the Neighbor-Joining method and Bootstrap test (1000 replicates). The evolutionary distances were computed using the Maximum Composite Likelihood method. The phylogenetic tree was generated using MEGA4 software. Phylogenetic analysis rooted to the 2009 influenza vaccine strain (A/Brisbane/10/2007).</p

    SGN-B7H4V, an investigational vedotin ADC directed to the immune checkpoint ligand B7-H4, shows promising activity in preclinical models

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    Background SGN-B7H4V is a novel investigational vedotin antibody–drug conjugate (ADC) comprising a B7-H4-directed human monoclonal antibody conjugated to the cytotoxic payload monomethyl auristatin E (MMAE) via a protease-cleavable maleimidocaproyl valine citrulline (mc-vc) linker. This vedotin linker-payload system has been clinically validated in multiple Food and Drug Administration approved agents including brentuximab vedotin, enfortumab vedotin, and tisotumab vedotin. B7-H4 is an immune checkpoint ligand with elevated expression on a variety of solid tumors, including breast, ovarian, and endometrial tumors, and limited normal tissue expression. SGN-B7H4V is designed to induce direct cytotoxicity against target cells by binding to B7-H4 on the surface of target cells and releasing the cytotoxic payload MMAE upon internalization of the B7-H4/ADC complex.Methods B7-H4 expression was characterized by immunohistochemistry across multiple solid tumor types. The ability of SGN-B7H4V to kill B7-H4-expressing tumor cells in vitro and in vivo in a variety of xenograft tumor models was also evaluated. Finally, the antitumor activity of SGN-B7H4V as monotherapy and in combination with an anti-programmed cell death-1 (PD-1) agent was evaluated using an immunocompetent murine B7-H4-expressing Renca tumor model.Results Immunohistochemistry confirmed B7-H4 expression across multiple solid tumors, with the highest prevalence in breast, endometrial, and ovarian tumors. In vitro, SGN-B7H4V killed B7-H4-expressing tumor cells by MMAE-mediated direct cytotoxicity and antibody-mediated effector functions including antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. In vivo, SGN-B7H4V demonstrated strong antitumor activity in multiple xenograft models of breast and ovarian cancer, including xenograft tumors with heterogeneous B7-H4 expression, consistent with the ability of vedotin ADCs to elicit a bystander effect. In an immunocompetent murine B7-H4-expressing tumor model, SGN-B7H4V drove robust antitumor activity as a monotherapy that was enhanced when combined with an anti-PD-1 agent.Conclusion The immune checkpoint ligand B7-H4 is a promising molecular target expressed by multiple solid tumors. SGN-B7H4V demonstrates robust antitumor activity in preclinical models through multiple potential mechanisms. Altogether, these preclinical data support the evaluation of SGN-B7H4V as a monotherapy in the ongoing phase 1 study of SGN-B7H4V in advanced solid tumors (NCT05194072) and potential future clinical combinations with immunotherapies
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