2,315 research outputs found

    Creation and assessment of a clinical predictive calculator and mortality associated with Candida krusei bloodstream infections

    Get PDF
    Abstract Background Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis. Methods We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively. Results We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and Ī²-lactam/Ī²-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81ā€“0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine. Conclusions Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics. </jats:sec

    Interactions of Bacterial Proteins with Host Eukaryotic Ubiquitin Pathways

    Get PDF
    Ubiquitination is a post-translational modification in which one or more 76 amino acid polypeptide ubiquitin molecules are covalently linked to the lysine residues of target proteins. Ubiquitination is the main pathway for protein degradation that governs a variety of eukaryotic cellular processes, including the cell-cycle, vesicle trafficking, antigen presentation, and signal transduction. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of many diseases including inflammatory and neurodegenerative disorders. Recent studies have revealed that viruses and bacterial pathogens exploit the host ubiquitination pathways to gain entry and to aid their survival/replication inside host cells. This review will summarize recent developments in understanding the biochemical and structural mechanisms utilized by bacterial pathogens to interact with the host ubiquitination pathways

    DEVELOPMENT OF A VERSATILE HIGH SPEED NANOMETER LEVEL SCANNING MULTI-PROBE MICROSCOPE

    Get PDF
    The motivation for development of a multi-probe scanning microscope, presented in this dissertation, is to provide a versatile measurement tool mainly targeted for biological studies, especially on the mechanical and structural properties of an intracellular system. This instrument provides a real-time, three-dimensional (3D) scanning capability. It is capable of operating on feedback from multiple probes, and has an interface for confocal photo-detection of fluorescence-based and single molecule imaging sensitivity. The instrument platform is called a Scanning Multi-Probe Microscope (SMPM) and enables 45 microm by 45 microm by 10 microm navigation of specimen with simultaneous optical and mechanical probing with each probe location being adjustable for collocation or for probing with known probe separations. The 3D positioning stage where the specimen locates was designed to have nanometer resolution and repeatability at 10 Hz scan speed with either open loop or closed loop operating modes. The fine motion of the stage is comprises three orthogonal flexures driven by piezoelectric actuators via a lever linkage. The flexures design is able to scan in larger range especially in z axis and serial connection of the stages helps to minimize the coupling between x, y and z axes. Closed-loop control was realized by the capacitance gauges attached to a rectangular block mounted to the underside of the fine stage upon which the specimen is mounted. The stage's performance was studied theoretically and verified by experimental test. In a step response test and using a simple proportional and integral (PI) controller, standard deviations of 1.9 nm 1.8 nm and 0.41 nm in the x, y and z axes were observed after settling times of 5 ms and 20 ms for the x and y axes. Scanning and imaging of biological specimen and artifact grating are presented to demonstrate the system operation. For faster, short range scanning, novel ultra-fast fiber scanning system was integrated into the xyz fine stage to achieve a super precision dual scanning system. The initial design enables nanometer positioning resolution and runs at 100 Hz scan speed. Both scanning systems are capable of characterization using dimensional metrology tools. Additionally, because the high-bandwidth, ultra-fast scanning system operates through a novel optical attenuating lever, it is physically separate from the longer range scanner and thereby does not introduce additional positioning noise. The dual scanner provides a fine scanning mechanism at relatively low speed and large imaging area using the xyz stage, and focus on a smaller area of interested in a high speed by the ultra-fast scanner easily. Such functionality is beneficial for researchers to study intracellular dynamic motion which requires high speed imaging. Finally, two high end displacement sensor systems, a knife edge sensor and fiber interferometer, were demonstrated as sensing solutions for potential feedback tools to boost the precision and resolution performance of the SMPM

    Suicide risk management in research on internet-based interventions for depression:A synthesis of the current state and recommendations for future research

    Get PDF
    BACKGROUND: The number of studies examining internet-based interventions (IBIs) for depression is increasing. Although many individuals with depression experience suicidal ideation, there is only insufficient information available on how to manage and support individuals at risk of suicide in IBI trials. Here, we examined the current practice regarding the management of individuals experiencing suicidal thoughts or behaviors in studies of IBIs for depression. METHODS: Information pertaining to the management of suicidality was extracted from 24 studies. Additionally, researchers in the field completed a questionnaire (nā€Æ=ā€Æ13) before being interviewed (nā€Æ=ā€Æ11) about their procedures and considerations regarding the management of suicidality. RESULTS: In most trials (Nā€Æ=ā€Æ17; 71%), individuals at risk of suicide were excluded based on varying criteria. Nā€Æ=ā€Æ7 studies used structured interviews and Nā€Æ=ā€Æ5 studies used single items of self-report questionnaires for assessing suicidality. The nature and degree of support provided to individuals at risk of suicide varied and only one intervention comprised suicide-specific content. LIMITATIONS: Most experts referred to research on interventions with some level of human support (e.g. written feedback) which might limit the representativeness of the results of the interviews for unguided interventions. CONCLUSIONS: Suicidality is often treated more as an exclusion criterion rather than a treatable condition in research on IBIs for depression. This paper provides an overview of the current practice and gives recommendations for the design of future trials

    Spintronic Terahertz Emitters: Status and Prospects from a Materials Perspective

    Get PDF
    Spintronic terahertz (THz) emitters, consisting of ferromagnetic (FM)/non-magnetic (NM) thin films, have demonstrated remarkable potential for use in THz time-domain spectroscopy and its exploitation in scientific and industrial applications. Since the discovery that novel FM/NM heterostructures can be utilized as sources of THz radiation, researchers have endeavored to find the optimum combination of materials to produce idealized spintronic emitters capable of generating pulses of THz radiation over a large spectral bandwidth. In the last decade, researchers have investigated the influence of a wide range of material properties, including the choice of materials and thicknesses of the layers, the quality of the FM/NM interface, and the stack geometry upon the emission of THz radiation. It has been found that particular combinations of these properties have greatly improved the amplitude and bandwidth of the emitted THz pulse. Significantly, studying the material properties of spintronic THz emitters has increased the understanding of the spin-to-charge current conversion processes involved in the generation of THz radiation. Ultimately, this has facilitated the development of spintronic heterostructures that can emit THz radiation without the application of an external magnetic field. In this review, we present a comprehensive overview of the experimental and theoretical findings that have led to the development of spintronic THz emitters, which hold promise for use in a wide range of THz applications. We summarize the current understanding of the mechanisms that contribute to the emission of THz radiation from the spintronic heterostructures and explore how the material properties contribute to the emission process
    • ā€¦
    corecore