Developing educational competencies for dissemination and implementation research training programs: An exploratory analysis using card sorts

Abstract Background With demand increasing for dissemination and implementation (D&I) training programs in the USA and other countries, more structured, competency-based, and tested curricula are needed to guide training programs. There are many benefits to the use of competencies in practice-based education such as the establishment of rigorous standards as well as providing an additional metrics for development and growth. As the first aim of a D&I training grant, an exploratory study was conducted to establish a new set of D&I competencies to guide training in D&I research. Methods Based upon existing D&I training literature, the leadership team compiled an initial list of competencies. The research team then engaged 16 additional colleagues in the area of D&I science to provide suggestions to the initial list. The competency list was then additionally narrowed to 43 unique competencies following feedback elicited from these D&I researchers. Three hundred additional D&I researchers were then invited via email to complete a card sort in which the list of competencies were sorted into three categories of experience levels. Participants had previous first-hand experience with D&I or knowledge translation training programs in the past. Participants reported their self-identified D&I expertise level as well as the country in which their home institution is located. A mean score was calculated for each competency based on their experience level categorization. From these mean scores, beginner-, intermediate-, and advanced-level tertiles were created for the competencies. Results The card sort request achieved a 41 % response rate (n = 124). The list of 43 competencies was organized into four broad domains and sorted based on their experience level score. Eleven competencies were classified into the “Beginner” category, 27 into “Intermediate,” and 5 into “Advanced.” Conclusions Education and training developers can use this competency list to formalize future trainings in D&I research, create more evidence-informed curricula, and enable overall capacity building and accompanying metrics in the field of D&I training and research.http://deepblue.lib.umich.edu/bitstream/2027.42/113065/1/13012_2015_Article_304.pd

A Cost-Effective Design for a Neutrino Factory

There have been active efforts in the U.S., Europe, and Japan on the design of a Neutrino Factory. This type of facility produces intense beams of neutrinos from the decay of muons in a high energy storage ring. In the U.S., a second detailed Feasibility Study (FS2) for a Neutrino Factory was completed in 2001. Since that report was published, new ideas in bunching, cooling and acceleration of muon beams have been developed. We have incorporated these ideas into a new facility design, which we designate as Study 2B (ST2B), that should lead to significant cost savings over the FS2 design.Comment: 46 pages, 38 figures; to be submitted to Physical Review Special Topics: Accelerators and Beam

A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA). While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms

Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1

\ua9 2024 The Author(s). AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis. Moreover, FLT3i induces the upregulation of signaling genes, and we show that multiple cytokines, including interleukin-3 (IL-3), can overcome FLT3 inhibition and send cells back into cycle. FLT3i leads to loss of AP-1 and RUNX1 chromatin binding, which is counteracted by IL-3. However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier

LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein.

The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESCs) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naive-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal pleckstrin homology (PH) membrane-binding domain. Although not essential for rapid unrestricted growth of ESCs under optimal conditions, the novel Gab1 variant (Gab1β) is required for LIF-mediated cell survival under conditions of limited nutrient availability. This enhanced survival is absolutely dependent upon a latent palmitoylation site that targets Gab1β directly to ESC membranes. These results show that constitutive association of Gab1 with membranes through a novel mechanism promotes LIF-dependent survival of murine ESCs in nutrient-poor conditions

Proton Drivers for Neutrino Factories: The CERN Approach

The paper describes the CERN approach for a proton driver for a Neutrino Factory. Two main layouts are presented: the so-called CERN Reference Scenario, based on a 2.2 GeV linac and an alternative one, based on a 30 GeV synchrotron. Both produce bunches of 1 ns (r.m.s.) and a beam power of 4 MW