Search

Sputter-deposited Pt-Au thin films have been reported to develop a hard, stable, nanocrystalline structure, yet little is known about how these characteristics vary with PtxAu1−x composition and process conditions. Toward this end, this document describes an extensive, combinatorial Pt-Au thin film library including characterized film compositions, structure, and properties. Complemented by kinematic Monte Carlo simulations of codeposition, a broad range of PtxAu1−x compositions (from x ∼ 0.02 to 0.93) was first established by sputtering with varied magnetron powers and gun tilt angles. The produced films were subsequently interrogated using automated nanoindentation, x-ray reflectivity, x-ray diffraction, atomic force microscopy, surface profilometry, four-point probe sheet resistance techniques, and wavelength dispersive spectroscopy in order to determine how hardness, modulus, density, surface roughness, structure, and resistivity vary with film stoichiometry and process parameters. Combinatorial films displayed an assortment of properties with the hardness of some films exceeding values reported previously for this material system. High hardness, high modulus, and low resistivity were generally attained when using increased deposition energy and reduced angle-of-incidence processes. Overall, the research identified promising, new PtxAu1−x compositions for future study and pinpointed strategies for improved deposition. [ABSTRACT FROM AUTHOR]

The different rate-limiting processes underlying ignition and self-propagating reactions in Al/Pt multilayers are examined through experiments and analytical modeling. Freestanding, ∼1.6 μm-thick Al/Pt multilayers of varied stoichiometries and nanometer-scale layer thicknesses ignite at temperatures below the melting point of both reactants (and eutectics) demonstrating that initiation occurs via solid-state mixing. Equimolar multilayers exhibit the lowest ignition temperatures when comparing structures having a specific bilayer thickness. An activation energy of 76.6 kJ/mol at. associated with solid state mass transport is determined from the model analysis of ignition. High speed videography shows that equimolar Al/Pt multilayers undergo the most rapid self-sustained reactions with wavefront speeds as large as 73 m/s. Al- and Pt-rich multilayers react at reduced rates (as low as 0.3 m/s), consistent with reduced heat of reaction and lower adiabatic temperatures. An analytical model that accounts for key thermodynamic properties, preliminary mixing along interfaces, thermal transport, and mass diffusion is used to predict the wavefront speed dependencies on bilayer thickness. Good fits to experimental data provide estimates for activation energy (51 kJ/mol at.) associated with mass transport subject to high heating rates and thermal diffusion coefficient of premixed interfacial volumes (2.8 × 10−6 m2/s). Pt dissolution into molten Al is identified as a rate-limiting step underlying high temperature propagating reactions in Al/Pt multilayers. [ABSTRACT FROM AUTHOR]

Background: Pediatric lung transplant patients are at risk for developing invasive fungal infections post-transplant. No consensus exists on optimal antifungal regimens and voriconazole, a common first-line agent, has been shown to cause hepatotoxicity. We describe a single-center experience utilizing a novel antifungal regimen of intravenous micafungin and nebulized amphotericin B immediately post-transplant with conversion to an azole at the time of hospital discharge and compare it to a historical cohort of patients who received voriconazole monotherapy throughout their immediate post-operative course., Methods: This is a retrospective review of patients in the age 0-18 who received a lung transplant from June 2016-May 2021. Data points collected included: demographic data, transplant date and discharge date, Aspergillus colonization, type of lung transplant, hospitalization and level of care information, induction and antifungal medication regimen; AST, ALT, GGT, bilirubin, and direct bilirubin at various timepoints; and respiratory and blood culture results. The two patient groups were compared by assessment of changes in LFTs and culture results., Results: Forty-two patients were included in the analysis, with 24 patients receiving micafungin and nebulized amphotericin and 18 patients receiving voriconazole. All patients in both groups experienced a post-operative elevation in at least one transaminase or bilirubin. More patients in the micafungin/amphotericin group had resolution of all abnormal LFTs by 1 month post-transplant (p = .036). Additionally, patients in the micafungin/amphotericin group experienced faster normalization of their LFTs compared with the voriconazole group (p < .001). Ten patients in the micafungin/amphotericin group and five patients in the voriconazole group were found to have fungal growth on culture post-transplant, but this difference was not found to be statistically significant (p = .507)., Conclusions: An antifungal regimen of micafungin and nebulized amphotericin B liposomal may be useful at decreasing the duration of elevated liver enzymes in pediatric patients in the immediate post-lung transplant period when compared with voriconazole monotherapy. Larger prospective studies looking at antifungal regimens in pediatric patients post-lung transplant are warranted., (© 2024 Wiley Periodicals LLC.)

Introduction: Multi-level dissemination strategies are needed to increase equitable access to effective treatment for high-risk outpatients with COVID-19, particularly among patients from disproportionately affected communities. Yet assessing population-level impact of such strategies can be challenging., Methods: In collaboration with key contributors in Colorado, we conducted a retrospective cohort study to evaluate a multi-level dissemination strategy for neutralizing monoclonal antibody (mAb) treatment. Real-world data included county-level, de-identified output from a statewide mAb referral registry linked with publicly available epidemiological data. Outcomes included weekly number of mAb referrals, unique referring clinicians, and COVID-19 hospitalization rates. We assessed weekly changes in outcomes after dissemination strategies launched in July 2021., Results: Overall, mAb referrals increased from a weekly average of 3.0 to 15.5, with an increase of 1.3 to 42.1 additional referrals per county in each post-period week ( p < .05). Number of referring clinicians increased from a weekly average of 2.2 to 9.7, with an additional 1.5 to 22.2 unique referring clinicians observed per county per week beginning 5 weeks post-launch ( p < .001). Larger effects were observed in communities specifically prioritized by the dissemination strategies. There were no observed differences in COVID-19 hospitalization rates between counties with and without mAb treatment sites., Conclusion: Real-world data can be used to estimate population impact of multi-level dissemination strategies. The launch of these strategies corresponded with increases in mAb referrals, but no apparent population-level effects on hospitalization outcomes. Strengths of this analytic approach include pragmatism and efficiency, whereas limitations include inability to control for other contemporaneous trends., Competing Interests: The authors have no conflicts of interest to disclose., (© The Author(s) 2023.)

The propagation of self-sustained formation reactions in sputter-deposited Co/Al multilayers is known to exhibit a design-dependent instability. Multilayers having thin bilayers (<55 nm period) exhibit stable propagating waves, whereas those with a larger period react unstably. The specific two-dimensional (2D) instability observed involves the transverse propagation of a band in front of a stalled front commonly referred to as a "spin band." Previous finite-element studies have shown that these instabilities are thermodynamically driven by the forward conduction of heat away from the flame front. However, the magnitude of that loss is inherently tied to the bilayer design in traditional bimetallic multilayers, which couples any proposed stability criteria to a varying critical diffusion distance. This work utilizes a recently developed class of materials known as "inert-mediated reactive multilayers" to decouple the thermodynamic and kinetic contributions to propagating wave stability by reducing the stored chemical energy density in normally stable bilayer designs. By depositing an inert product phase (B2-CoAl) within the mid-plane of Co and Al reactant layers, spin instabilities arise as a function of both diluted volume and critical diffusion distance. From there, a stability criterion is determined for Co/Al multilayers based on enthalpy loss from the reaction zone, and its physical significance is explored.

Background: Neutralizing monoclonal antibody (mAb) treatment for COVID-19 prevents hospitalization and death but is underused, especially in racial/ethnic minority and rural populations. Reasons for underuse and inequity may include community member lack of awareness or healthcare access barriers, among others. This study assessed mAbs community awareness and opportunities for improving equitable mAb access., Methods: A concurrent mixed methods study including surveys and focus groups with adults with high-risk conditions or their proxy decision-makers. Surveys and focus group guides addressed diffusion of innovation theory factors. Descriptive statistics and Fisher's exact method was used to report and compare survey findings by race and ethnicity. Rapid qualitative methods were used for focus group analysis., Results: Surveys from 515 individuals (460 English, 54 Spanish, 1 Amharic), and 8 focus groups (6 English, 2 Spanish) with 69 participants, completed June 2021 to January 2022. Most survey respondents (75%) had heard little or nothing about mAbs, but 95% would consider getting mAb treatment. Hispanic/Latino and Non-Hispanic People of Color (POC) reported less awareness, greater concern about intravenous infusions, and less trust in mAb safety and effectiveness than White, Non-Hispanic respondents. Focus group themes included little awareness but high interest in mAb treatment and concerns about cost and access barriers such as lacking established sources of care and travel from rural communities. Focus groups revealed preferences for broad-reaching but tailored messaging strategies using multiple media and trusted community leaders., Conclusions: Despite unfamiliarity with mAb treatment, most respondents were open to receiving mAbs or recommending mAbs to others. While mAb messaging should have broad reach "to everyone everywhere," racial and geographic disparities in awareness and trust about mAbs underscore need for tailored messaging to promote equitable access. Care processes should address patient-level barriers like transportation, insurance, or primary care access. COVID-19 treatment dissemination strategies should promote health equity., Competing Interests: “One author reports receiving grants from NIH, CDC, DoD, and pharmaceutical companies outside the submitted work. The other authors have declared that no competing interests exist.”, (Copyright: © 2022 Kwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is an urgent need to identify and address factors influencing uptake and equitable access to monoclonal antibody (mAb) treatment for high-risk outpatients with COVID-19., Objective: To assess clinician knowledge, beliefs, and experiences regarding obtaining mAb treatment for eligible patients., Design and Participants: Survey of clinicians (N = 374) practicing in the state of Colorado who care for patients with COVID-19 in primary care, emergency medicine, and other clinical settings., Main Measure(s): Diffusion of innovation theory concepts including knowledge, perceived strength of evidence, barriers, and experience with, ease of use, preparedness, and feasibility, appropriateness, and acceptability of mAb referral systems and processes., Key Results: Most respondents indicated little to no knowledge about mAb therapies for COVID-19 (67%, 74%, 77%, for bamlanivimab, bamlanivimab+etesivimab, and casirivimab+imdevimab, respectively). About half reported little to no familiarity with eligibility criteria (50.9%) and did not know the strength of evidence (31%, 43%, 52%, for bamlanivimab, bamlanivimab+etesivimab, and casirivimab+imdevimab, respectively). Lack of knowledge or confidence in treatment was a top barrier to mAbs use; other barriers included complicated referral processes, patients not eligible when seen, and out-of-pocket costs concerns. Respondents rated four mAb referral steps as generally acceptable, appropriate, and feasible to complete in their primary outpatient clinical setting. Only 24% indicated their clinical setting was very prepared to facilitate referrals, 40% had ever referred a patient for mAbs, and 43% intended to refer a patient in the next month., Conclusions: Clinician education on strength of evidence and eligibility criteria for mAbs is needed. However, education alone is not sufficient. Given the urgent need to rapidly scale up access to treatment and reduce hospitalizations and death from COVID-19, more efficient, equitable systems and processes for referral and delivery of care, such as those coordinated by health systems, public health departments, or disaster management services, are warranted., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: The identification of pathologically altered neutrophil granulocyte migration patterns bears strong potential for surveillance and prognostic scoring of diseases. We recently identified a strong correlation between impaired neutrophil motility and the disease stage of myelodysplastic syndrome (MDS). Here, we apply this assay to study quantitively increased neutrophils of a patient suffering from a rare leukemia subtype, atypical chronic myeloid leukemia (aCML)., Methods: A 69-year-old male was analyzed in this study. Besides routine analyses, we purified the patient's neutrophils from peripheral whole blood and studied their migration behavior using time-lapse video microscopy in a standardized assay. These live cell migration analyses also allowed for the quantification of cell morphology. Furthermore, the cells were stained for the markers CD15, CD16, fMLPR, CXCR1 and CXCR2., Results: Despite cytoreductive therapy with hydroxyurea, the patient's WBC and ANC were poorly controlled and severe dysgranulopoiesis with hypogranularity was observed. Neutrophils displayed strongly impaired migration when compared to healthy controls and migrating cells exhibited a more flattened-out morphology than control neutrophils. Because of a detected CSF3R (p.T618I) mutation and constitutional symptoms treatment with ruxolitinib was initiated. Within 1 week of ruxolitinib treatment, the cell shape normalized and remained indistinguishable from healthy control neutrophils. However, neutrophil migration did not improve over the course of ruxolitinib therapy but was strikingly altered shortly before a sinusitis with fever and bleeding from a gastric ulcer. Molecular work-up revealed that under ruxolitinib treatment, the CSF3R clone was depleted, yet the expansion of a NRAS mutated subclone was promoted., Conclusion: These results demonstrate the usefulness of neutrophil migration analyses to uncover corresponding alterations of neutrophil migration in rare myeloid neoplasms. Furthermore, in addition to monitoring migration the determination of morphological features of live neutrophils might represent a useful tool to monitor the effectiveness of therapeutic approaches.

Autonomous migration is a central characteristic of immune cells, and changes in this function have been correlated to the progression and severity of diseases. Hence, the identification of pathologically altered leukocyte migration patterns might be a promising approach for disease surveillance and prognostic scoring. However, because of the lack of standardized and robust assays, migration patterns have not been clinically exploited so far. In this study, we introduce an easy-to-use and cross-laboratory, standardized two-dimensional migration assay for neutrophil granulocytes from peripheral blood. By combining time-lapse video microscopy and automated cell tracking, we calculated the average migration of neutrophils from 111 individual participants of the German Heinz Nixdorf Recall MultiGeneration study under steady-state, formyl-methionyl-leucyl-phenylalanine-, CXCL1-, and CXCL8-stimulated conditions. Comparable values were obtained in an independent laboratory from a cohort in Belgium, demonstrating the robustness and transferability of the assay. In a double-blinded retrospective clinical analysis, we found that neutrophil migration strongly correlated with the Revised International Prognostic Scoring System scoring and risk category of myelodysplastic syndrome (MDS) patients. In fact, patients suffering from high-risk subtypes MDS with excess blasts I or II displayed highly significantly reduced neutrophil migration. Hence, the determination of neutrophil migration patterns might represent a useful tool in the surveillance of MDS. Taken together, we suggest that standardized migration assays of neutrophils and other leukocyte subtypes might be broadly applicable as prognostic and surveillance tools for MDS and potentially for other diseases., (Copyright © 2018 by The American Association of Immunologists, Inc.)

A 36-year-old man came to the outpatient dermatology department with asymptomatic, skin-coloured to white/yellow, firm papules on his prepuce. Over the last 10 years he had received different treatments for condylomata accuminata, with no effect. After shave excision, the diagnosis of idiopathic calcinosis cutis was made.

Rare reports of splenic rupture have been associated with filgrastim treatment during peripheral blood progenitor cell (PBPC) mobilization in allogeneic donors. We performed a prospective study of spleen volume change in 309 normal donors who received filgrastim according to local institutional practices. Splenic assessments consisted of ultrasonography and clinical examination at baseline and on the first day of leukapheresis in 304 donors. Of these, 90 donors were also examined 2 and 4 days after the first leukapheresis and 7 days after the last leukapheresis. Median spleen volume increased 1.47-fold (range: 0.63 to 2.60) on the first leukapheresis day and declined to near pretreatment levels at 7 days after last leukapheresis. Nine percent of donors had > or =2-fold increase in splenic volume. Spleen palpability did not correlate with change in spleen volume. No donors experienced a splenic rupture. There was no correlation between change in spleen volume and filgrastim dosage, number of doses/day, peak absolute neutrophil count (ANC), CD34+ yield, or donor baseline weight. Most donors experienced > or =1 adverse event, with 6 donors reporting serious adverse events. We conclude that the increase in splenic volume during PBPC mobilization in donors was transient, and that filgrastim was well tolerated in this study. This trial was registered at www.ClinicalTrials.gov as NCT00115128.