Combining to innovate: A collaborative interprofessional learning approach to delivering Tobacco Use Prevention and Cessation (TUPAC) education for undergraduate oral health students

This paper provides a description of a pilot project in Tobacco Use Prevention and Cessation (TUPAC) in response to a national and international trend to include TUPAC curriculum components in the clinical education of undergraduate oral health students. In order to deliver quality brief intervention strategies for smokers a need to adequately prepare oral health students was identified during student clinical placements. An interprofessional (IP) project team was established with membership from the University of Adelaide’s School of Dentistry, QuitSA, Cancer Council SA, the South Australian Dental Service (SADS) Somerton Park and TAFESA’s Faculty of Dental Studies to streamline the efficient use of resources and most importantly draw on a diverse range of interprofessional health care expertise. On the website for The UK Centre for the Advancement of Interprofessional Education (CAIPE) (2002) it states that “Interprofessional education occurs when two or more professions learn from and about each other to improve collaboration and the quality of care”. Through interprofessional learning (IPL) in classroom and clinical settings, second year Bachelor and Advanced Diploma oral health students were provided with the opportunity to develop an understanding of the respective roles of each health professional responsible for delivering positive health initiatives in the area of TUPAC. With limited national oral health curricula in the area of TUPAC, the project team forged links with the University of Manitoba’s Dental Hygiene Program, and the convenor of the TUPAC in Dental and Dental Hygiene Undergraduate Education European Workshops for curriculum benchmarking against evidence based criteria. Most importantly as the IP concept of health care considers the patient at the centre of the health care team, assessment was designed to encourage a patient centred approach through the review and analysis of a clinical case study. A formal evaluation of this project is currently in progress, however results were not yet available at the time of publication

Voltage-dependent behavior of a "ball-and-chain" gramicidin channel

This is the published version. Copyright 1997 by Elsevier.The channel-forming properties of two analogs of gramicidin, gramicidin-ethylenediamine (gram-EDA), and gramicidin-N,N-dimethylethylenediamine (gram-DMEDA) were studied in planar lipid bilayers, using protons as the permeant ion. These peptides have positively charged amino groups tethered to their C-terminal ends via a linker containing a carbamate group. Gram-DMEDA has two extra methyl groups attached to the terminal amino group, making it a bulkier derivative. The carbamate groups undergo thermal cis-trans isomerization on the 10–100-ms time scale. The conductance behavior of gram-EDA is found to be markedly voltage dependent, whereas the behavior of gram-DMEDA is not. In addition, voltage affects the cis-trans ratios of the carbamate groups of gram-EDA, but not those of gram-DMEDA. A model is proposed to account for these observations, in which voltage can promote the binding of the terminal amino group of gram-EDA to the pore in a "ball-and-chain" fashion. The bulkiness of the gram-DMEDA derivative prevents this binding

Blinded Outcome Assessment Was Infrequently Used and Poorly Reported in Open Trials

Objective Unblinded outcome assessment can lead to biased estimates of treatment effect in randomised trials. We reviewed published trials to assess how often blinded assessment is used, and whether its use varies according to the type of outcome or assessor. Design and setting A review of parallel group, individually randomised phase III trials published in four general medical journals (BMJ, Journal of the American Medical Association, The Lancet, and New England Journal of Medicine) in 2010. Main outcome measures Whether assessment of the primary outcome was blinded, and whether this differed according to outcome or assessor type. Results We identified 258 eligible trials. Of these, 106 (41%) were reported as double-blind, and 152 (59%) as partially or fully open-label (that is, they included some groups who were unblinded, such as patients, those delivering the intervention, or those in charge of medical care). Of the 152 open trials, 125 required outcome assessment. Of these 125 trials, only 26% stated that outcome assessment was blinded; 51% gave no information on whether assessment was blinded or not. Furthermore, 18% of trials did not state who performed the assessment. The choice of outcome type (e.g. instrument measured, rated, or naturally occurring event) did not appear to influence whether blinded assessment was performed (range 24-32% for the most common outcome types). However, the choice of outcome assessor did influence blinding; independent assessors were blinded much more frequently (71%) than participant (5%) or physician (24%) assessors. Despite this, open trials did not use independent assessors any more frequently than double-blind trials (17% vs. 18% respectively). Conclusions Blinding of outcome assessors is infrequently used and poorly reported. Increased use of independent assessors could increase the frequency of blinded assessment

Phi-values in protein folding kinetics have energetic and structural components

Phi-values are experimental measures of how the kinetics of protein folding is changed by single-site mutations. Phi-values measure energetic quantities, but are often interpreted in terms of the structures of the transition state ensemble. Here we describe a simple analytical model of the folding kinetics in terms of the formation of protein substructures. The model shows that Phi-values have both structural and energetic components. In addition, it provides a natural and general interpretation of "nonclassical" Phi-values (i.e., less than zero, or greater than one). The model reproduces the Phi-values for 20 single-residue mutations in the alpha-helix of the protein CI2, including several nonclassical Phi-values, in good agreement with experiments.Comment: 15 pages, 3 figures, 1 tabl

Partnership through co-creation: lessons learnt at the University of Adelaide

This paper describes three exemplars of practice inspired by emerging evidence that student-staff partnerships have the potential to significantly enhance many areas of higher education. Students and academics at the University of Adelaide have successfully implemented this collaborative approach across a range of learning and teaching contexts. The Design Thinking Framework, developed by the Hasso Plattner Institute of Design at Stanford University, was utilised at a faculty, program, and course level to frame each of the exemplars, due to its implicit approach to creativity, collaborative development, and achievement of solutions. The iterative nature of the framework facilitated a review cycle for continuous improvement in each Students-as-Partners’ initiative. Analysing the outcomes of each exemplar has identified common hallmarks of successful partnership, and these indicators have the potential to contribute to the growing body of evidence that defines best practice in this pedagogy.Catherine Snelling, Beth R Loveys, Sophie Karanicolas, Nathan James Schofield, William Carlson-Jones, Joanne Weissgerber, Ruby Edmonds, and Jenny Ng

Dominant Folding Pathways of a WW Domain

We investigate the folding mechanism of the WW domain Fip35 using a realistic atomistic force field by applying the Dominant Reaction Pathways (DRP) approach. We find evidence for the existence of two folding pathways, which differ by the order of formation of the two hairpins. This result is consistent with the analysis of the experimental data on the folding kinetics of WW domains and with the results obtained from large-scale molecular dynamics (MD) simulations of this system. Free-energy calculations performed in two coarse-grained models support the robustness of our results and suggest that the qualitative structure of the dominant paths are mostly shaped by the native interactions. Computing a folding trajectory in atomistic detail only required about one hour on 48 CPU's. The gain in computational efficiency opens the door to a systematic investigation of the folding pathways of a large number of globular proteins

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Natural product (L)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1

Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21WAF−1. We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cells. We used a fluorescence polarization assay to screen for small molecules that disrupt the binding of MSI1 to its consensus RNA binding site. One of the top hits was (−)-gossypol (Ki = 476 ± 273 nM), a natural product from cottonseed, known to have potent anti-tumor activity and which has recently completed Phase IIb clinical trials for prostate cancer. Surface plasmon resonance and nuclear magnetic resonance studies demonstrate a direct interaction of (−)-gossypol with the RNA binding pocket of MSI1. We further showed that (−)-gossypol reduces Notch/Wnt signaling in several colon cancer cell lines having high levels of MSI1, with reduced SURVIVIN expression and increased apoptosis/autophagy. Finally, we showed that orally administered (−)-gossypol inhibits colon cancer growth in a mouse xenograft model. Our study identifies (−)-gossypol as a potential small molecule inhibitor of MSI1-RNA interaction, and suggests that inhibition of MSI1's RNA binding activity may be an effective anti-cancer strategy

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.Comment: 40 pages, 13 PostScript figure

Investigating the effect of independent blinded digital image assessment on the STOP GAP trial

Background Blinding is the process of keeping treatment assignment hidden and is used to minimise the possibility of bias. Trials at high risk of bias have been shown to report larger treatment effects than low risk studies. In dermatology, one popular method of blinding is to have independent outcome assessors who are unaware of treatment allocation assessing the end point using digital photographs. However, this can be complex, expensive and time-consuming. The objective of this study was to compare the effect of blinded and unblinded outcome assessment on the results of the STOP GAP trial. Methods The STOP GAP trial compared prednisolone to ciclosporin in treating pyoderma gangrenosum. Participants’ lesions were measured at baseline and 6 weeks to calculate the primary outcome, speed of healing. Independent blinded assessors obtained measurements from digital photographs using specialist software. In addition, unblinded treating clinicians estimated lesion area by measuring length and width. The primary outcome was determined using blinded measurements where available, otherwise unblinded measurements were used (method referred to as trial measurements). In this study, agreement between the trial and unblinded measurements was determined using the intraclass correlation coefficient (ICC). The STOP GAP primary analysis was repeated using unblinded measurements only. We introduced differential and non-differential error in unblinded measurements and investigated the effect on the STOP GAP primary analysis. Results 86 (80%) of the 108 patients were assessed using digital images. Agreement between trial and unblinded measurements was excellent (ICC=0.92 at baseline; 0.83 at 6 weeks). There was no evidence that the results of the trial primary analysis differed according to how the primary outcome was assessed (p-value for homogeneity = 1.00). Conclusions Blinded digital image assessment in STOP GAP did not meaningfully alter trial conclusions compared with unblinded assessment. However, as the process brought added accuracy and credibility to the trial it was considered worthwhile. These findings question the usefulness of digital image assessment in a trial with an objective outcome and where bias is not expected to be excessive. Further research should investigate if there are alternative, less complex ways of incorporating blinding in clinical trials