Experiential Learning with Ketamine: A Mixed-Methods Exploratory Study on Prescription and Perception

Annette M Ilg,1 Christine P Beltran,2 Jenny A Shih,3,4 Tuyen T Yankama,5 Margaret M Hayes,6,&ast; Ari L Moskowitz6,7,&ast; 1Division of Emergency Critical Care, Department of Emergency Medicine, Mass General Brigham, Boston, MA, USA; 2Carl J, Shapiro Institute for Education and Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 4Department of Pulmonary and Critical Care, Brigham and Women’s Hospital, Boston, MA, USA; 5Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA; 6Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 7Division of Critical Care Medicine, Department of Medicine, Montefiore Medical Center, Bronx, New York, NY, USA&ast;These authors contributed equally to this workCorrespondence: Annette M Ilg, Mass General Brigham, Department of Emergency Medicine, Division of Critical Care, 75 Francis St, Boston, MA, 02115, USA, Email [email protected]: Incorporating unfamiliar therapies into practice requires effective longitudinal learning and the optimal way to achieve this is debated. Though not a novel therapy, ketamine in critical care has a paucity of data and variable acceptance, with limited research describing intensivist perceptions and utilization. The Coronavirus-19 pandemic presented a particular crisis where providers rapidly adapted analgosedation strategies to achieve prolonged, deep sedation due to a surge of severe acute respiratory distress syndrome (ARDS).Question: How does clinical experience with ketamine impact the perception and attitude of clinicians toward this therapy?Methods: We conducted a mixed-methods study using quantitative ketamine prescription data and qualitative focus group data. We analyzed prescription patterns of ketamine in a tertiary academic ICU during two different time points: pre-COVID-19 (March 1–June 30, 2019) and during the COVID-19 surge (March 1–June 30, 2020). Two focus groups (FG) of critical care attendings were held, and data were analyzed using the Framework Method for content analysis.Results: Four-hundred forty-six medical ICU patients were mechanically ventilated (195 pre-COVID-19 and 251 during COVID-19). The COVID-19 population was more likely to receive ketamine (81[32.3%] vs 4 [2.1%], p < 0.001). Thirteen respondents participated across two FG sessions (Pre-COVID = 8, Post-COVID=5). The most prevalent attitude among our respondents was discomfort, with three key themes identified as follows: 1) lack of evidence regarding ketamine, 2) lack of personal experience, and 3) desire for more education and protocols.Conclusion: Despite a substantial increase in ketamine prescription during COVID-19, intensivists continued to feel discomfort with utilization. Factors contributing to this discomfort include a lack of evidence, a lack of experience, and a desire for more education and protocols. Increase in experience with ketamine alone was not sufficient to minimize provider discomfort. These findings should inform future curricula and call for process improvement to optimize continuing education.Keywords: analgosedation, continuing education, learning theory, ketamine, critical car

Dirac Gauginos, Negative Supertraces and Gauge Mediation

In an attempt to maximize General Gauge Mediated parameter space, I propose simple models in which gauginos and scalars are generated from disconnected mechanisms. In my models Dirac gauginos are generated through the supersoft mechanism, while independent R-symmetric scalar masses are generated through operators involving non-zero messenger supertrace. I propose several new methods for generating negative messenger supertraces which result in viable positive mass squareds for MSSM scalars. The resultant spectra are novel, compressed and may contain light fermionic SM adjoint fields.Comment: 16 pages 3 figure

Soft Spectrum in Yukawa-Gauge Mediation

We introduce a model independent parametrization for a subclass of gauge mediated theories, which we refer to as Yukawa-gauge mediation. Within this formalism we study the resulting soft masses in the visible spectrum. We find general expressions for the gaugino and scalar masses. Under generic conditions, the gaugino mass is screened, vanishing at first order in the SUSY breaking scale.Comment: 22 pages, 4 figures; v2: minor corrections, published versio

Bounds on SCFTs from Conformal Perturbation Theory

The operator product expansion (OPE) in 4d (super)conformal field theory is of broad interest, for both formal and phenomenological applications. In this paper, we use conformal perturbation theory to study the OPE of nearly-free fields coupled to SCFTs. Under fairly general assumptions, we show that the OPE of a chiral operator of dimension $\Delta = 1+\epsilon$ with its complex conjugate always contains an operator of dimension less than $2 \Delta$. Our bounds apply to Banks-Zaks fixed points and their generalizations, as we illustrate using several examples.Comment: 36 pages; v2: typos fixed, minor change

Simplified R-Symmetry Breaking and Low-Scale Gauge Mediation

We argue that some of the difficulties in constructing realistic models of low-scale gauge mediation are artifacts of the narrow set of models that have been studied. In particular, much attention has been payed to the scenario in which the Goldstino superfield in an O'Raifeartaigh model is responsible for both supersymmetry breaking and R-symmetry breaking. In such models, the competing problems of generating sufficiently massive gauginos while preserving an acceptably light gravitino can be quite challenging. We show that by sharing the burdens of breaking supersymmetry and R-symmetry with a second field, these problems are easily solved even within the O'Raifeartaigh framework. We present explicit models realizing minimal gauge mediation with a gravitino mass in the eV range that are both calculable and falsifiable.Comment: 31 pages, 4 figures, references added, minor change

Anomalous Dimensions of Non-Chiral Operators from AdS/CFT

Non-chiral operators with positive anomalous dimensions can have interesting applications to supersymmetric model building. Motivated by this, we develop a new method for obtaining the anomalous dimensions of non-chiral double-trace operators in N=1 superconformal field theories (SCFTs) with weakly-coupled AdS duals. Via the Hamiltonian formulation of AdS/CFT, we show how to directly compute the anomalous dimension as a bound state energy in the gravity dual. This simplifies previous approaches based on the four-point function and the OPE. We apply our method to a class of effective AdS5 supergravity models, and we find that the binding energy can have either sign. If such models can be UV completed, they will provide the first calculable examples of SCFTs with positive anomalous dimensions.Comment: 38 pages, 2 figures, refs adde

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

&lt;p&gt;Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.&lt;/p&gt; &lt;p&gt;Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.&lt;/p&gt; &lt;p&gt;Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.&lt;/p&gt

Recombinant Trimeric HA Protein Immunogenicity of H5N1 Avian Influenza Viruses and Their Combined Use with Inactivated or Adenovirus Vaccines

[[abstract]]Background:The highly pathogenic avian influenza (HPAI) H5N1 virus continues to cause disease in poultry and humans. The hemagglutinin (HA) envelope protein is the primary target for subunit vaccine development.Methodology/Principal Findings:We used baculovirus-insect cell expression to obtain trimeric recombinant HA (rHA) proteins from two HPAI H5N1 viruses. We investigated trimeric rHA protein immunogenicity in mice via immunizations, and found that the highest levels of neutralizing antibodies resulted from coupling with a PELC/CpG adjuvant. We also found that the combined use of trimeric rHA proteins with (a) an inactivated H5N1 vaccine virus, or (b) a recombinant adenovirus encoding full-length HA sequences for prime-boost immunization, further improved antibody responses against homologous and heterologous H5N1 virus strains. Data from cross-clade prime-boost immunization regimens indicate that sequential immunization with different clade HA antigens increased antibody responses in terms of total IgG level and neutralizing antibody titers.Conclusion/Significance:Our findings suggest that the use of trimeric rHA in prime-boost vaccine regimens represents an alternative strategy for recombinant H5N1 vaccine development