Promoting deeper learning in pharmacy education using team-based learning

Background. The benefit of deep learning compared with surface learning is the ability to retrieve, apply and integrate previously learnt knowledge rather than simply memorising course content most likely to be evaluated during assessments. Team-based learning (TBL) is an educational strategy that echoes the purpose of deeper learning. Objectives. To identify whether TBL as a teaching strategy increases pharmacy students’ understanding of theoretical work. Method. Fourth-year pharmacy students completed a questionnaire consisting of biographical data (gender, age and ethnicity) and 16 questions on their understanding of course content. A total of 183 students (91.5%) participated after giving informed consent that their data may be included in the study. Results. The results indicated that, due to the implementation of TBL in the course, students perceived that they learnt more and made more effort, experienced increased understanding of content, perceived higher knowledge retention, performed better during assessments in the module where TBL was implemented and felt that course outcomes were achieved more easily. Conclusion. TBL as a teaching strategy could potentially promote deeper learning of course content

If you say so:A mixed-method study of hospital mergers and quality of care

Background: Despite a lack of supporting evidence, hospitals continue to merge in pursuit of quality improvements. Purpose: We seek to develop a more thorough understanding of the quality effects of hospital mergers by integrating various theoretical perspectives using a mixed-methods design. Methodology: Quantitatively, we tested the quality effect of all consummated hospital mergers in the Netherlands between 2008 and 2014 on 15 quality indicators (with 82 measurements at hospital, department, and disease levels) using a difference-in-difference approach with Bonferroni correction. Qualitatively, we conducted three comparative case studies to examine how hospital executives, managers, and medical professionals perceive the quality impact of hospital mergers. Results: Our quantitative results reveal few significant effects of hospital mergers on quality of care at all levels. After applying Bonferroni correction, two quality indicators are negatively associated with hospital mergers. However, the qualitative results indicate that hospital staff have positive perceptions of the mergers’ quality implications, resulting from scale and shock effects. Conclusion: The perceptions of hospital staff regarding mergers diametrically oppose their measurable effects. However, the operationalization of quality by hospital staff members differs considerably from the way it is quantitatively measured. The positive perceptions of hospital staff toward mergers could further contribute to the institutionalization of mergers as a quality improvement strategy. Practice Implications: Hospital managers seeking measurable quality improvements should be wary of merging, despite potential positive perceptions toward it within the organization. In case they do decide to merge, mitigating difficulties in the postmerger integration processes seem most pertinent to achieve measurable effects

Orbital and spin physics in LiNiO2 and NaNiO2

We derive a spin-orbital Hamiltonian for a triangular lattice of e_g orbital degenerate (Ni^{3+}) transition metal ions interacting via 90 degree superexchange involving (O^{2-}) anions, taking into account the on-site Coulomb interactions on both the anions and the transition metal ions. The derived interactions in the spin-orbital model are strongly frustrated, with the strongest orbital interactions selecting different orbitals for pairs of Ni ions along the three different lattice directions. In the orbital ordered phase, favoured in mean field theory, the spin-orbital interaction can play an important role by breaking the U(1) symmetry generated by the much stronger orbital interaction and restoring the threefold symmetry of the lattice. As a result the effective magnetic exchange is non-uniform and includes both ferromagnetic and antiferromagnetic spin interactions. Since ferromagnetic interactions still dominate, this offers yet insufficient explanation for the absence of magnetic order and the low-temperature behaviour of the magnetic susceptibility of stoichiometric LiNiO_2. The scenario proposed to explain the observed difference in the physical properties of LiNiO_2 and NaNiO_2 includes small covalency of Ni-O-Li-O-Ni bonds inducing weaker interplane superexchange in LiNiO_2, insufficient to stabilize orbital long-range order in the presence of stronger intraplane competition between superexchange and Jahn-Teller coupling.Comment: 33 pages, 12 postscript figures, uses iopams.sty . This article features in New Journal of Physics as part of a Focus Issue on Orbital Physics - all contributions may be freely accessed at (http://stacks.iop.org/1367-2630/6/i=1/a=E05). The published version of this article may be found at http://stacks.iop.org/1367-2630/7/12

Ribosomal proteins produced in excess are degraded by the ubiquitin-proteasome system

Ribosome assembly is an essential process that consumes prodigious quantities of cellular resources. Ribosomal proteins cannot be overproduced in Saccharomyces cerevisiae because the excess proteins are rapidly degraded. However, the responsible quality-control (QC) mechanisms remain poorly characterized. Here, we demonstrate that overexpression of multiple proteins of the small and large yeast ribosomal subunits is suppressed. Rpl26 overexpressed from a plasmid can be detected in the nucleolus and nucleoplasm, but it largely fails to assemble into ribosomes and is rapidly degraded. However, if the endogenous RPL26 loci are deleted, plasmid-encoded Rpl26 assembles into ribosomes and localizes to the cytosol. Chemical and genetic perturbation studies indicate that overexpressed ribosomal proteins are degraded by the ubiquitin-proteasome system, and not by autophagy. Inhibition of the proteasome led to accumulation of multiple endogenous ribosomal proteins in insoluble aggregates, consistent with the operation of this QC mechanism in the absence of ribosomal protein overexpression. Our studies reveal that ribosomal proteins that fail to assemble into ribosomes are rapidly distinguished from their assembled counterparts and are ubiquitinated and degraded within the nuclear compartment

Online treatment of persistent complex bereavement disorder, posttraumatic stress disorder, and depression symptoms in people who lost loved ones during the COVID-19 pandemic:study protocol for a randomized controlled trial and a controlled trial

Background: Losing a loved one during the COVID-19 pandemic is a potentially traumatic loss that may result in symptoms of persistent complex bereavement disorder (PCBD), posttraumatic stress disorder (PTSD), and depression. To date, grief-specific cognitive-behavioural therapy (CBT) has mostly been delivered through individual face-to-face formats, while studies have shown that online treatment also yields promising results. Offering treatment online is now more than ever relevant during the pan demic and may offer important benefits compared with face-to-face CBT, such as lower costs and higher accessibility. Our expectation is that grief-specific online CBT is effective in reducing PCBD, PTSD, and depression symptoms. Objective: Our aim is to evaluate the short-term and long-term effectiveness of grief-specific online CBT in reducing PCBD, PTSD, and depression symptom-levels for adults who lost a loved one during the COVID-19 pandemic. Method: This study consists of two parts. In part 1, a two-armed (unguided online CBT versus waitlist controls) randomized controlled trial will be conducted. In part 2, a two-armed (guided online CBT versus unguided online CBT) controlled trial will be conducted. Symptoms of PCBD, PTSD, and depression will be assessed via telephone interviews at pre-treatment/pre-waiting period, post-treatment/post-waiting period, and six months post-treatment. Potential participants are people who lost a loved one at least three months earlier during the COVID-19 pandemic with clinically relevant levels of PCBD, PTSD, and/or depression. Analysis of covariance and multilevel modelling will be performed. Discussion: This is one of the first studies examining the effectiveness of online grief-specific CBT. More research is needed before implementing online grief-specific CBT into clinical practice

PIKES Analysis Reveals Response to Degraders and Key Regulatory Mechanisms of the CRL4 Network

Co-opting Cullin4 RING ubiquitin ligases (CRL4s) to inducibly degrade pathogenic proteins is emerging as a promising therapeutic strategy. Despite intense efforts to rationally design degrader molecules that co-opt CRL4s, much about the organization and regulation of these ligases remains elusive. Here, we establish protein interaction kinetics and estimation of stoichiometries (PIKES) analysis, a systematic proteomic profiling platform that integrates cellular engineering, affinity purification, chemical stabilization, and quantitative mass spectrometry to investigate the dynamics of interchangeable multiprotein complexes. Using PIKES, we show that ligase assemblies of Cullin4 with individual substrate receptors differ in abundance by up to 200-fold and that Cand1/2 act as substrate receptor exchange factors. Furthermore, degrader molecules can induce the assembly of their cognate CRL4, and higher expression of the associated substrate receptor enhances degrader potency. Beyond the CRL4 network, we show how PIKES can reveal systems level biochemistry for cellular protein networks important to drug development

Teaching introductory undergraduate Physics using commercial video games

Commercial video games are increasingly using sophisticated physics simulations to create a more immersive experience for players. This also makes them a powerful tool for engaging students in learning physics. We provide some examples to show how commercial off-the-shelf games can be used to teach specific topics in introductory undergraduate physics. The examples are selected from a course taught predominantly through the medium of commercial video games.Comment: Accepted to Physics Education, Fig1 does not render properly in this versio

Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases

SCF (Skp1-Cullin-F-box) ubiquitin ligases comprise several dozen modular enzymes that have diverse roles in biological regulation. SCF enzymes share a common catalytic core containing Cul1⋅Rbx1, which is directed toward different substrates by a variable substrate receptor (SR) module comprising 1 of 69 F-box proteins bound to Skp1. Despite the broad cellular impact of SCF enzymes, important questions remain about the architecture and regulation of the SCF repertoire, including whether SRs compete for Cul1 and, if so, how this competition is managed. Here, we devise methods that preserve the in vivo assemblages of SCF complexes and apply quantitative mass spectrometry to perform a census of these complexes (the “SCFome”) in various states. We show that Nedd8 conjugation and the SR exchange factor Cand1 have a profound effect on shaping the SCFome. Together, these factors enable rapid remodeling of SCF complexes to promote biased assembly of SR modules bound to substrate

Single subunit degradation of WIZ, a lenalidomide- and pomalidomide dependent substrate of E3 ubiquitin ligase CRL4^(CRBN)

Immunomodulators (IMiDs) are an effective class of drugs used to treat blood cancers. IMiDs are believed to work by recruiting protein targets containing a β-hairpin motif for ubiquitination by E3 ubiquitin ligase complexes composed of cereblon (CRBN), Cullin-4a (CUL4a), DNA Damage Binding protein-1 (DDB1), and Ring Box-1 (RBX1). The ubiquitinated protein is subsequently degraded by the proteasome. By characterizing the repertoire of proteins that show an increased physical association with CRBN after IMiD treatment, we identified a novel IMiD substrate, Widely Interspaced Zinc Finger Motifs (WIZ). WIZ contains a C2H2 zinc finger domain, like several other substrates that were previously characterized. We demonstrate that IMiDs stabilize physical association of WIZ with CRBN, deplete WIZ steady state protein levels in a way that is dependent on E3 ligase activity, and enhance the rate of its degradation. Notably, proteins that assemble with WIZ are co-recruited to CRBN by IMiDs but are not degraded, illustrating the potential of targeted protein degradation to eliminate individual subunits of a protein complex. These findings suggest that systematic characterization of the full repertoire of proteins that are targeted for degradation by IMiD compounds will be required to better understand their biological effects