Continuous Infusion of Escalated Doses of Amphotericin B Deoxycholate: An Open-Label Observational Study

Amphotericin B deoxycholate (AmB-d) remains a mainstay of antifungal therapy for immunocompromised patients, despite being associated with significant therapy-related toxicity. Because continuous infusion of AmB-d is better tolerated than traditional administration over 2-6 hours, we evaluated escalation of the AmB-d dose in 33 patients (31 of whom were neutropenic), for whom the initial dosage of AmB-d (1 mg/kg/day) was gradually increased to 2.0 mg/kg/day when renal function remained stable and the drug was tolerated. Dose escalation was possible without delay in 28 patients. Median duration of AmB-d therapy was 16 days (range, 7-72 days). Infusion-related reactions accompanied 2-fold decrease in creatine clearance was observed in 5 patients, and the decrease was dose-limiting in only 1 patient; no dialysis was required. In conclusion, continuous infusion of AmB-d escalated to 2.0 mg/kg/day seems not to cause additional impairment of vital organ functions and to be well tolerated by most patient

The Effect of Restrictions at the US/Mexico Border on Employment Outcomes

&nbsp; In March of 2020, the United States instituted new restrictions on the US/Mexico border that severely limited travel. This policy made it very hard for Mexican consumers to cross the border and engage in economic activities. This paper asks how the border restrictions affected US employment outcomes in the period after the closure, based on pre-existing vulnerability defined by ratio of foreign to domestic population. I estimate this effect using a difference-in-differences strategy and an event study accounting for the effects of the COVID-19 pandemic utilizing a created term of vulnerability in the interaction. I found evidence that the closure affected counties with a higher vulnerability more than those with low vulnerability after the closure relative to before. </p

Active topolectrical circuits

The transfer of topological concepts from the quantum world to classical mechanical and electronic systems has opened fundamentally new approaches to protected information transmission and wave guidance. A particularly promising technology are recently discovered topolectrical circuits that achieve robust electric signal transduction by mimicking edge currents in quantum Hall systems. In parallel, modern active matter research has shown how autonomous units driven by internal energy reservoirs can spontaneously self-organize into collective coherent dynamics. Here, we unify key ideas from these two previously disparate fields to develop design principles for active topolectrical circuits (ATCs) that can self-excite topologically protected global signal patterns. Realizing autonomous active units through nonlinear Chua diode circuits, we theoretically predict and experimentally confirm the emergence of self-organized protected edge oscillations in one- and two-dimensional ATCs. The close agreement between theory, simulations and experiments implies that nonlinear ATCs provide a robust and versatile platform for developing high-dimensional autonomous electrical circuits with topologically protected functionalities.Comment: 10 pages, 4 figures, includes supplementary material. This version adds 2D experiment

Rapid Colonization with Methicillin-Resistant Coagulase-Negative Staphylococci After Surgery

Background: Antimicrobial resistance may compromise the efficacy of antibiotic prophylaxis before surgery. The aim of this study was to measure susceptibility and clonal distribution of coagulase-negative staphylococci (CoNS) colonizing the skin around the surgery access site before and after the procedure. Methods: From March to September 2004, a series of 140 patients undergoing elective major abdominal surgery were screened for CoNS colonization at admission and 5days after surgery. All isolates were tested for antibiotic susceptibility and genotyped by pulsed-field gel electrophoresis (PFGE). Results: Colonization rates with CoNS at admission and after surgery were 85% and 55%, respectively. The methicillin-resistant CoNS rate increased from 20% at admission to 47% after surgery (P=0.001). The PFGE pattern after surgery revealed more patients colonized with identical clones: 8/140 patients (8/119 strains) and 26/140 patients (26/77 strains), respectively (P<0.001). Conclusions: Our results suggest rapid recolonization of disinfected skin by resistant nosocomial CoNS. Larger studies, preferably among orthopedic or cardiovascular patients, are required to clarify whether standard antibiotic prophylaxis with first- or second-generation cephalosporins for CoNS infections may be compromised if the patient requires an additional intervention 5days or more after the initial surger

Hemophagocytic macrophages constitute a major compartment of heme oxygenase expression in sepsis

Schaer DJ, Schaer CA, Schoedon G, Imhof A, Kurrer MO. Hemophagocytic macrophages constitute a major compartment of heme oxygenase expression in sepsis. Objectives: Uncontrolled macrophage activation with hemophagocytosis is a distinctive feature of hemophagocytic syndromes (HPS). We examined whether lympho-histiocytic infiltration of the bone marrow and liver, as well as hemo-/erythrophagocytosis also occurs during sepsis and whether this process could account for the increased production of anti-inflammatory heme-oxygenase (HO-1) products observed during sepsis. Methods: Hemophagocytosis and expression of CD163, HO-1, ferritin as well as CD8 and granzyme-B were examined in post-mortem bone marrow samples from 28 patients with sepsis and from eight control patients. Results: Comparison of samples from non-septic patients with samples from patients with fatal sepsis revealed that the latter group displayed dense lympho-histiocytic bone marrow infiltration with CD163(+)/HO-1(+)/ferritin(+) macrophages as well as with CD8(+) and granzyme-B(+) T-cells. Hemophagocytosis with prominent phagocytosis of erythroid cells was readily apparent in septic patients, implying that this process is a likely stimulus for the up-regulation of macrophage HO-1 expression. Conclusions: Lympho-histiocytic activation with hemophagocytosis is a shared pathophysiologic mechanism in HPS and sepsis. Furthermore, the association of hemophagocytosis with an increase in HO-1 expression may indicate a novel role for this apparently futile process as a negative regulator of inflammation

HautTief Multidisciplinary Educational Program for Patients with Psoriasis or Atopic Dermatitis: A Randomized Controlled Study

BACKGROUND Improving health-related quality of life (HRQoL), disease severity, and treatment adherence through patient education is an increasingly important, yet relatively new area in dermatology. This randomized controlled trial aims to contribute to this growing area of research by exploring the effects of a 9-week educational program for patients with chronic skin diseases. OBJECTIVE The aim of the study was to evaluate the effect of a multidisciplinary educational program on HRQoL and disease severity in patients with psoriasis or atopic dermatitis (AD). METHODS Sixty-four patients with diagnosed psoriasis or AD were recruited from University Hospital Zurich and randomized (1:1) to the intervention or control group. To assess HRQoL, the following self-reported questionnaires were used: Dermatology Life Quality Index (DLQI), Skindex-29, EuroQol-5D (EQ-5D), RAND 36-Item Short Form Survey (SF-36), and Beck Depression Inventory (BDI) to measure depression symptoms. Psoriasis Area and Severity Index (PASI) and the Eczema Area and Severity Index (EASI) were used to capture disease extent. These scores were assessed at four study visits, which were performed at baseline and 3, 6, and 9 months after the start of the program. RESULTS At month 6, an improvement of at least 25% in BDI was recorded in 15 (68.2%) of 22 patients in the intervention group and 6 (27.3%) of 22 patients in the control group (difference 40.9%, p = 0.016). 53.3% (16 of 30) of patients achieved an improvement in one subdomain of the SF-36 score (role limitations due to emotional problems) at 6-month follow-up, compared with 23.1% (6 of 26) of those not attending the educational program (difference 30.2%; p = 0.042). No significant differences in DLQI, Skindex-29, EQ-5D, PASI, and EASI between both groups at the three time points were found. CONCLUSION An educational program may improve HRQoL and depression status of patients with psoriasis or AD

Realizing efficient topological temporal pumping in electrical circuits

Quantized adiabatic transport can occur when a system is slowly modulated over time. In most realizations however, the efficiency of such transport is reduced by unwanted dissipation, back-scattering, and non-adiabatic effects. In this work, we realize a topological adiabatic pump in an electrical circuit network that supports remarkably stable and long-lasting pumping of a voltage signal. We further characterize the topology of our system by deducing the Chern number from the measured edge band structure. To achieve this, the experimental setup makes use of active circuit elements that act as time-variable voltage-controlled inductors.Comment: main (5 pages, 3 figures) plus supplement (8 pages, 4 figures