5 research outputs found

    Machine Learning in Additive Manufacturing: A Review

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    In this review article, the latest applications of machine learning (ML) in the additive manufacturing (AM) field are reviewed. These applications, such as parameter optimization and anomaly detection, are classified into different types of ML tasks, including regression, classification, and clustering. The performance of various ML algorithms in these types of AM tasks are compared and evaluated. Finally, several future research directions are suggested

    Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children

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    BACKGROUND Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited PK data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. OBJECTIVES To describe the pharmacokinetics of LAmB in children aged 1-17 years with suspected or documented IFD. METHODS Thirty-five children were treated with LAmB at dosages of 2.5-10 mg kg(-1) daily. Samples were taken at baseline and at 0.5-2.0 hourly intervals for twenty-four hours after receipt of the first dose (n=35 patients) and on the final day of therapy (n=25 patients). LAmB was measured using high performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. RESULTS An evolution in PK was observed during the course of therapy resulting in a proportion of patients (n=13) having significantly higher maximum serum concentration (Cmax) and area under the concentration time curve (AUC0-24) later in the course of therapy, without evidence of drug accumulation (Cmin accumulation ratio, AR < 1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24 and probability of nephrotoxicity (OR 2.37; 95% CI 1.84-3.22, p=0.004). CONCLUSIONS LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation or observed clinical factors

    The Conserved Herpesviridae Protein Kinase (CHPK) of Gallid alphaherpesvirus 3 (GaHV3) Is Required for Horizontal Spread and Natural Infection in Chickens

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    We have formerly identified the conserved herpesvirus protein kinase (CHPK) as essential for horizontal transmission of Marek&rsquo;s disease virus (MDV). Thus far, it has been confirmed that the mutation of the invariant lysine (K) of CHPKs abrogates kinase activity and that CHPK activity is required for MDV horizontal transmission. Since CHPK is conserved among all members of the Herpesviridae, we hypothesized that CHPK, and specifically its kinase activity, is important for the horizontal transmission of other herpesviruses. To test this hypothesis, we utilized our experimental and natural infection model in chickens with MD vaccine strain 301B/1 of Gallid alphaherpesvirus 3 (GaHV3). First, we mutated the invariant lysine (K) 157 of 301B/1 CHPK to alanine (A) and determined whether it was required for horizontal transmission. To confirm the requirement of 301B/1 CHPK activity for transmission, a rescued virus was generated in which the A157 was changed back to a K (A157K). Despite both the CHPK mutant (K157A) and rescuant (A157K) viruses having replication defects in vivo, only the CHPK mutant (K157A) was unable to spread to contact chickens, while both wild-type and rescuant (A157K) viruses transmitted efficiently, confirming the importance of CHPK activity for horizontal spread. The data confirm that CHPK is required for GaHV3 transmission and suggest that the requirement of avian CHPKs for natural infection is conserved

    The Influence of Powder Particle Size Distributions on Mechanical Properties of Alloy 718 by Laser Powder Bed Fusion

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    Currently, metallic powders for laser powder bed fusion (LPBF) primarily come in two commercially available powder size distributions (PSDs): 15+/45− for non-reactive powders and 15+/63− for reactive powders. These powders are generally produced via gas atomization processes that create highly spherical particles with a Gaussian PSD. Because of the standard deviation within a Gaussian distribution, only small portions of the total product are used for LPBF applications. This screening process makes the other particle sizes a waste product and, thus, increases processing costs. The non-reactive 718 powder was printed with both the typical PSD of 15+/45− and a wider bimodal experimental PSD. Compared to conventional 718, the 718 alloys with bimodal PSD shows less than a 0.2% difference in density, and insignificant change in mechanical behavior. Electron backscattered diffraction studies revealed that grain sizes and morphology were similar between the two sample sets, but bimodal 718 alloy has a slightly greater degree of large grains. The study suggests that particles with wide or bimodal size distributions show promise in producing equivalent high-quality products without sacrificing mechanical properties
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