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Tumor External Aspects Mediate Major T-DM1 Opposition throughout HER2-Positive Breast Cancer Tissue.
C. Goodwin, A. Verma, C. P. Arevalo, et al., medRxiv, 2020, https//doi.org/10.1101/2020.11.06.20227215; S. M. Kissler, C. Tedijanto, E. Goldstein, Y. H. Grad, and M. Lipsitch, Science 368860-868, 2020, https//doi.org/10.1126/science.abb5793).Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus "preimmune" ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting ithe 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.Serratia marcescens is an emerging pathogen with increasing clinical importance due to its intrinsic resistance to several classes of antibiotics. The chromosomally encoded drug efflux pumps contribute to antibiotic resistance and represent a major challenge for the treatment of bacterial infections. The ABC-type efflux pump MacAB was previously linked to macrolide resistance in Escherichia coli and Salmonella enterica serovar Typhimurium. The role of the MacAB homolog in antibiotic resistance of S. RO-1-9213 marcescens is currently unknown. We found that an S. marcescens mutant lacking the MacAB pump did not show increased sensitivity to the macrolide antibiotic erythromycin but was significantly more sensitive to aminoglycoside antibiotics and polymyxins. We also showed that, in addition to its role in drug efflux, the MacAB efflux pump is required for swimming motility and biofilm formation. We propose that the motility defect of the ΔmacAB mutant is due, at least in part, to the loss of functional flagella on the bfrom oxidative stress in Salmonella enterica serovar Typhimurium, is not characterized in S. marcescens We show the role of the MacAB efflux pump in S. marcescens protection from aminoglycoside antibiotics and polymyxins, modulation of bacterial motility, and biofilm formation, and we illustrate the essential role for this pump in bacterial survival during oxidative stress. Our findings make the MacAB efflux pump an attractive target for inhibition to gain control over S. marcescens infections.
Overuse of lumbar imaging is common in the emergency department (ED). Few trials have examined interventions to address this. We evaluated the effectiveness of a multifaceted intervention to implement guideline recommendations for low back pain in the emergency department.

We conducted a stepped-wedge, cluster-randomised trial in four EDs in New South Wales, Australia. After a 13-month control phase of usual care, the EDs received a multifaceted intervention to support guideline-endorsed care in a random order, based on a computer-generated random sequence, every 4 weeks over a 4-month period. All sites were followed up for at least 3 months. The primary outcome was the proportion of low back pain presentations receiving lumbar imaging. Secondary healthcare utilisation outcomes included prescriptions of opioid and non-opioid pain medicines, inpatient admissions, length of ED stay, specialist referrals and re-presentations. Clinician beliefs and knowledge about low back pain care were measured before and aent guideline recommendations for low back pain care decreased lumbar imaging in the ED; however, it did reduce opioid prescriptions without adversely affecting patient outcomes.
ACTRN12617001160325.
It is uncertain if a multifaceted intervention to implement guideline recommendations for low back pain care decreased lumbar imaging in the ED; however, it did reduce opioid prescriptions without adversely affecting patient outcomes.Trial registration number ACTRN12617001160325.
To compare the insulin infusion management of critically ill patients by nurses using either a common standard (ie, human completion of insulin infusion protocol steps) or smart agent (SA) system that integrates the electronic health record and infusion pump and automates insulin dose selection.

A within subjects design where participants completed 12 simulation scenarios, in 4 blocks of 3 scenarios each. Each block was performed with either the manual standard or the SA system. The initial starting condition was randomised to manual standard or SA and alternated thereafter.

A simulation-based human factors evaluation conducted at a large academic medical centre.

Twenty critical care nurses.

A systems engineering intervention, the SA, for insulin infusion management.

The primary study outcomes were error rates and task completion times. Secondary study outcomes were perceived workload, trust in automation and system usability, all measured with previously validated scales.

The SA system produced significantly fewer dose errors compared with manual calculation (17% (n=20) vs 0, p<0.
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