86,763 research outputs found
Investigational Antifungal Agents for Invasive Mycoses: A Clinical Perspective
No full textTreatment of invasive fungal infections (IFIs) remains challenging, because of the limitations of the current antifungal agents (ie, mode of administration, toxicity, and drug-drug interactions) and the emergence of resistant fungal pathogens. Therefore, there is an urgent need to expand our antifungal armamentarium. Several compounds are reaching the stage of phase II or III clinical assessment. These include new drugs within the existing antifungal classes or displaying similar mechanism of activity with improved pharmacologic properties (rezafungin and ibrexafungerp) or first-in-class drugs with novel mechanisms of action (olorofim and fosmanogepix). Although critical information regarding the performance of these agents in heavily immunosuppressed patients is pending, they may provide useful additions to current therapies in some clinical scenarios, including IFIs caused by azole-resistant Aspergillus or multiresistant fungal pathogens (eg, Candida auris, Lomentospora prolificans). However, their limited activity against Mucorales and some other opportunistic molds (eg, some Fusarium spp.) persists as a major unmet need.Recent advances in antifungal drug development offer hope for expanded choices for management of difficult to treat or recalcitrant invasive mycoses, such as resistant invasive candidiasis or aspergillosis and scedosporiosis/lomentosporosis. However, clinical perspectives for the treatment of mucormycosis remains limited
Role and interpretation of antifungal susceptibility testing for the management of invasive fungal infections
No full textInvasive fungal infections (IFIs) are associated with high mortality rates and timely ap-propriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among Candida and Aspergillus spp., the major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate. Specifically, the utility of AST is limited by the delay in obtaining results and the lack of pharmacodynamic correlation between minimal inhibitory concentration (MIC) values and clinical outcome, particularly for molds. Clinical breakpoints for Candida spp. have been substantially revised over time and appear to be reliable for the detection of azole and echinocandin resistance and for outcome prediction, especially for non-neutropenic patients with candidemia. However, data are lacking for neutropenic patients with invasive candidiasis and some non-albicans Candida spp. (notably emerging Candida auris). For Aspergillus spp., AST is not routinely performed, but may be indicated according to the epidemiological context in the setting of emerging azole resistance among A. fumigatus. For non-Aspergillus molds (e.g., Mucorales, Fusarium or Scedosporium spp.), AST is not routinely recommended as interpretive criteria are lacking and many confounders, mainly host factors, seem to play a predominant role in responses to antifungal therapy. This review provides an overview of the pre-clinical and clinical pharmacodynamic data, which constitute the rationale for the use and interpretation of AST testing of yeasts and molds in clinical practice
Navigating the Uncertainties of COVID-19–Associated Aspergillosis: A Comparison With Influenza-Associated Aspergillosis
No full textInvasive pulmonary aspergillosis (IPA) is increasingly recognized as a life-threatening superinfection of severe respiratory viral infections, such as influenza. The pandemic of Coronavirus Disease 2019 (COVID-19) due to emerging SARS-CoV-2 rose concern about the eventuality of IPA complicating COVID-19 in intensive care unit patients. A variable incidence of such complication has been reported, which can be partly attributed to differences in diagnostic strategy and IPA definitions, and possibly local environmental/epidemiological factors. In this article, we discuss the similarities and differences between influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA). Compared to IAPA, the majority of CAPA cases have been classified as putative rather than proven/probable IPA. Distinct physiopathology of influenza and COVID-19 may explain these discrepancies. Whether CAPA represents a distinct entity is still debatable and many questions remain unanswered, such as its actual incidence, the predisposing role of corticosteroids or immunomodulatory drugs, and the indications for antifungal therapy
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
ECILrecommendations for the use of biological markers for the diagnosis of invasivefungal diseases in leukemic patients and hematopoietic SCT recipients
No full textAlso By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation
No full textThe desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters
John F. Kennedy telegram to Roosevelt
No full textJersey Homesteads (later the Borough of Roosevelt) was established in the 1930s as an agro-industrial cooperative community. It was established specifically for urban Jewish garment workers, many of whom had emigrated from Europe. President John F. Kennedy sent a telegram to the citizens of Roosevelt, New Jersey, apologizing for not being able to attend the memorial dedication in honor of former President Franklin Delano Roosevelt. (Jersey Homesteads became Roosevelt in 1945 in honor of the president.) President Kennedy expressed his gratitude to the people of Roosevelt for constructing the memorial, and commented that it will serve as a constant reminder of Roosevelt's good works
Logarithmic variance profiles and the corresponding f-1 spectra of temperature fluctuations in turbulent Rayleigh-Bénard convection
No full textWe report experimental results for the temperature variance 2(z) and the corresponding frequency spectra P(f) in turbulent Rayleigh-Bénard convection (RBC) in a cylindrical sample of aspect ratioT= D/L = 1:00 (D = 1:12 m is the diameter and L = 1:12 m the height). The measurements were conducted in the Rayleigh-number range 1011 < Ra < 1:35 1014 and Pr ' 0:8. For Ra = 1:35x1014, 2(z) could be described well by a logarithmic dependence on the vertical position z in a range of z 1 < z < z 2 with z 1 ' 70 and z 2 = 0:1L. Here L=(2Nu) is the thickness of a thin thermal sublayer adjacent to the horizontal plate where the heat flux (denoted by the Nusselt number Nu) is carried mostly by thermal diffusion. In the log layer, we found that the temperature spectra had a significant frequency range over which P(f) f with close to 1. As Ra decreased, increased so that the log layer became thinner. At Ra = 2:05 1011, z 2 < z 1 and therefore there was no range for a log layer. Correspondingly, the temperature spectrum near the horizontal plate did not have the f1 scaling form either
Maine author Franklin F. Gould recalls his first glimpse of the outside world
No full textMaine author Franklin F. Gould recalls his first glimpse of the outside world as he relates how, as a young farm boy in the late 1800\u27s, he drove his father\u27s horses on an errand to an icebound river
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