Perceptions of online surgical-focused learning amongst surgeons during the COVID pandemic: A scoping review 2020-22.

INTRODUCTION: During the COVID pandemic many centres adopted e-learning as a tool to adhere to social distancing recommendations while continuing to provide ongoing postgraduate medical education. We aimed to complete this scoping review in order to map experience and perceptions amongst surgeons and surgical trainees to remote learning during the COVID pandemic. METHODS: Using Arksey and O'Malley's five step model for conducting a scoping review, a systematic search strategy was undertaken across three online databases SCOPUS, MEDLINE and Web of Science. Only original articles in English in the field of postgraduate education in surgery were included. RESULTS: 44 studies were selected for review. Of these 44, 21 were studies of perception of a newly developed e-learning tool/platform. 17 were surveys of surgeon's attitudes towards e-learning during the COVID pandemic. The remaining 6 studies were studies of knowledge or skills acquired through new e-learning, which included a survey of experience. The United States was the most common country of origin with General Surgery the most represented surgical speciality. Response rates across all three study subgroups were on average >60%. Surgeon's experience of e-learning was reported in only positive terms in 86% (n = 38/44) of studies. CONCLUSIONS: This paper is informative in that it focuses specifically on surgeons' perceptions of a e-learning tools used in addition to skills or knowledge gained. Positive e-learning experience reported in these studies may lead to more blended learning curriculums being developed, deployed and evaluated going forward.

Advances in e-learning in undergraduate clinical medicine: a systematic review.

BACKGROUND: E-learning is recognised as a useful educational tool and is becoming more common in undergraduate medical education. This review aims to examine the scope and impact of e-learning interventions on medical student learning in clinical medicine, in order to aid medical educators when implementing e-learning strategies in programme curricula. METHODS: A systematic review compliant with PRISMA guidelines that appraises study design, setting and population, context and type of evaluations. Specific search terms were used to locate articles across nine databases: MEDLINE/PubMed, ScienceDirect, EMBASE, Cochrane Library, ERIC, Academic Search Complete, CINAHL, Scopus and Google Scholar. Only studies evaluating e-learning interventions in undergraduate clinical medical education between January 1990 and August 2021 were selected. Of the 4,829 papers identified by the search, 42 studies met the inclusion criteria. RESULTS: The 42 studies included varied in scope, cognitive domain, subject matter, design, quality and evaluation. The most popular approaches involved multimedia platforms (33%) and case-based approaches (26%), were interactive (83%), asynchronous (71%) and accessible from home (83%). Twelve studies (29%) evaluated usability, all of which reported positive feedback. Competence in use of technology, high motivation and an open attitude were key characteristics of successful students and preceptors. CONCLUSIONS: Medical education is evolving consistently to accommodate rapid changes in therapies and procedures. In today's technologically adept world, e-learning is an effective and convenient pedagogical approach for the teaching of undergraduate clinical medicine.

Importance and vulnerability of the world's water towers.

Mountains are the water towers of the world, supplying a substantial part of both natural and anthropogenic water demands1,2. They are highly sensitive and prone to climate change3,4, yet their importance and vulnerability have not been quantified at the global scale. Here we present a global water tower index (WTI), which ranks all water towers in terms of their water-supplying role and the downstream dependence of ecosystems and society. For each water tower, we assess its vulnerability related to water stress, governance, hydropolitical tension and future climatic and socio-economic changes. We conclude that the most important (highest WTI) water towers are also among the most vulnerable, and that climatic and socio-economic changes will affect them profoundly. This could negatively impact 1.9 billion people living in (0.3 billion) or directly downstream of (1.6 billion) mountainous areas. Immediate action is required to safeguard the future of the world's most important and vulnerable water towers.

Integrating threshold concepts with reflective practice: Discussing a theory-based approach for curriculum refinement in dental education.

INTRODUCTION: The theory of threshold concepts (TCs) is a burgeoning area of educational research and curriculum reform. This study describes and reviews the TCs literature, describes the differences between TCs and threshold learning outcomes (TLOs) and seeks to promote discussion on using an integrated reflective practice approach to facilitate the translation of TCs into fulfilment of TLOs. A worked example is included in this study to explore the challenges inherent in this task but also the learning gains to be made for both staff and students in this endeavour. INTERSECTION OF REFLECTIVE CLINICAL PRACTICE AND THRESHOLD CONCEPTS: Reflection is intrinsic to all aspects of learning and is a vital characteristic of developing competence in the health professions. Further, the need for explicit teaching and assessment of reflection in health professions education is recognised. We suggest that the identification of TCs can help to scaffold reflective processes in dentistry and argue that TCs may achieve a bridging function between theory and practice when used in conjunction with reflective writing and dialogue. This study provides a discussion of the complexities and challenges involved as well as an explicit example of the process involved for 1 TC in 1 particular discipline-removable prosthodontics. DISCUSSION: Reflective practice is recognised by the authors as a pedagogical tool to support the acquisition of threshold concepts. An example is provided of integrating reflective practice tasks with identified TCs in curricula which shows the potential of reflective dialogue and discourse as vehicles to make TCs explicit as well as facilitate the attainment of threshold learning outcomes or graduate attributes. This is an ongoing process, and although the fully revised curriculum is not ready to be translated to other contexts, we suggest it is beneficial to start working towards the integration of reflective practice tasks and identified TLOs as part of curriculum refinement-rather than adding to a crowded curriculum. We suggest such an integrated approach can harness the challenges inherent in discipline-specific contexts to bridge the theory-practice nexus for students and permit staff greater flexibility in the teaching and assessment of such traditionally difficult areas. SUMMARY: We propose a way of thinking about curriculum change by integrating threshold concepts with the explicit use and assessment of reflective practice tasks as a means to achieve threshold learning outcomes and professional attributes identified by accrediting bodies. We provide an overview of the literature in this area and an example of our approach in linking reflective practice with newly identified threshold concepts in our School. We welcome further discussion, debate and collaboration in this area.

Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children.

The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.

Restoration of PPP2CA expression reverses epithelial-to-mesenchymal transition and suppresses prostate tumour growth and metastasis in an orthotopic mouse model.

BACKGROUND: Emergence of castration-resistance in prostate cancer (PCa) is invariably associated with aggressive and metastatic disease. Previously, we reported promotion of castration-resistance upon downregulation of PPP2CA (encoding catalytic subunit of protein phosphatase 2A (PP2A), α-isoform); however, its role in PCa growth and metastasis remained undetermined. METHODS: PPP2CA was overexpressed/silenced in PCa cells by stable transfection. Gene expression was examined by reverse transcription polymerase chain reaction, immunoblot and immunofluorescence analyses, and transcriptional activity measured by luciferase-based promoter-reporter assay. Effect on PCa phenotype was studied in vitro and in orthotopic mouse model, and immunohistochemical/histological analyses performed to assess proliferation/apoptosis and confirm metastatic lesions. RESULTS: An inverse association of PPP2CA expression was observed with epithelial-to-mesenchymal transition (EMT) and aggressive PCa phenotype. PPP2CA restoration resulted in decreased nuclear accumulation and transcriptional activity of ß-catenin/NF-κB, and restitution of their activity abrogated PPP2CA-induced EMT reversal and suppression of PCa invasiveness. Akt mediated PPP2CA loss-induced nuclear accumulation of ß-catenin/NF-κB through inactivation of Gsk3-ß and IκB-α, respectively. Animal studies revealed a suppressive effect of PPP2CA expression on PCa growth and metastasis. CONCLUSIONS: Our findings suggest that PPP2CA downregulation serves as a molecular link between gain of castration-resistance and aggressive PCa phenotype, and its restoration could be an effective preventive/therapeutic approach against the advanced disease.

Experimental investigation of the mechanical stiffness of periodic framework-patterned elastomers.

Recent advances in the cataloguing of three-dimensional nets mean a systematic search for framework structures with specific properties is now feasible. Theoretical arguments about the elastic deformation of frameworks suggest characteristics of mechanically isotropic networks. We explore these concepts on both isotropic and anisotropic networks by manufacturing porous elastomers with three different periodic net geometries. The blocks of patterned elastomers are subjected to a range of mechanical tests to determine the dependence of elastic moduli on geometric and topological parameters. We report results from axial compression experiments, three-dimensional X-ray computed tomography imaging and image-based finite-element simulations of elastic properties of framework-patterned elastomers.

Toxicology study assessing efficacy and safety of repeated administration of lipid/DNA complexes to mouse lung.

For gene therapy to improve lung function in cystic fibrosis (CF) subjects, repeated administration of the gene transfer agent over the lifetime of patients is likely to be necessary. This requirement limits the utility of adenoviral and adeno-associated viral vectors (both previously evaluated in CF gene therapy trials) because of induced adaptive immune responses that render repeated dosing ineffective. For CF gene therapy trials, non-viral vectors are currently the only viable option. We previously showed that the cationic lipid formulation GL67A is the most efficient of several non-viral vectors analysed for airway gene transfer. Here, we assessed the efficacy and safety of administering 12 inhaled doses of GL67A complexed with pGM169, a CpG-free plasmid encoding human CFTR complementary DNA, into mice. We show that repeated administration of pGM169/GL67A to murine lungs is feasible, safe and achieves reproducible, dose-related and persistent gene expression (>140 days after each dose) using an aerosol generated by a clinically relevant nebuliser. This study supports progression into the first non-viral multidose lung trial in CF patients.

Unification and classification of two-dimensional crystalline patterns using orbifolds.

The concept of an orbifold is particularly suited to classification and enumeration of crystalline groups in the euclidean (flat) plane and its elliptic and hyperbolic counterparts. Using Conway's orbifold naming scheme, this article explicates conventional point, frieze and plane groups, and describes the advantages of the orbifold approach, which relies on simple rules for calculating the orbifold topology. The article proposes a simple taxonomy of orbifolds into seven classes, distinguished by their underlying topological connectedness, boundedness and orientability. Simpler `crystallographic hyperbolic groups' are listed, namely groups that result from hyperbolic sponge-like sections through three-dimensional euclidean space related to all known genus-three triply periodic minimal surfaces (i.e. the P, D, Gyroid, CLP and H surfaces) as well as the genus-four I-WP surface.

Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung.

We use both large and small animal models in our pre-clinical evaluation of gene transfer agents (GTAs) for cystic fibrosis (CF) gene therapy. Here, we report the use of a large animal model to assess three non-viral GTAs: 25 kDa-branched polyethyleneimine (PEI), the cationic liposome (GL67A) and compacted DNA nanoparticle formulated with polyethylene glycol-substituted lysine 30-mer. GTAs complexed with plasmids expressing human cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA were administered to the sheep lung (n=8 per group) by aerosol. All GTAs gave evidence of gene transfer and expression 1 day after treatment. Vector-derived mRNA was expressed in lung tissues, including epithelial cell-enriched bronchial brushing samples, with median group values reaching 1-10% of endogenous CFTR mRNA levels. GL67A gave the highest levels of expression. Human CFTR protein was detected in small airway epithelial cells in some animals treated with GL67A (two out of eight) and PEI (one out of eight). Bronchoalveolar lavage neutrophilia, lung histology and elevated serum haptoglobin levels indicated that gene delivery was associated with mild local and systemic inflammation. Our conclusion was that GL67A was the best non-viral GTA currently available for aerosol delivery to the sheep lung, led to the selection of GL67A as our lead GTA for clinical trials in CF patients.

Circular dichroism in biological photonic crystals and cubic chiral nets.

Nature provides impressive examples of chiral photonic crystals, with the notable example of the cubic so-called srs network (the label for the chiral degree-three network modeled on SrSi2) or gyroid structure realized in wing scales of several butterfly species. By a circular polarization analysis of the band structure of such networks, we demonstrate strong circular dichroism effects: The butterfly srs microstructure, of cubic I4(1)32 symmetry, shows significant circular dichroism for blue to ultraviolet light, that warrants a search for biological receptors sensitive to circular polarization. A derived synthetic structure based on four like-handed silicon srs nets exhibits a large circular polarization stop band of a width exceeding 30%. These findings offer design principles for chiral photonic devices.

The chiral structure of porous chitin within the wing-scales of Callophrys rubi.

The structure of the porous three-dimensional reticulated pattern in the wing scales of the butterfly Callophrys rubi (the Green Hairstreak) is explored in detail, via scanning and transmission electron microscopy. A full 3D tomographic reconstruction of a section of this material reveals that the predominantly chitin material is assembled in the wing scale to form a structure whose geometry bears a remarkable correspondence to the srs net, well-known in solid state chemistry and soft materials science. The porous solid is bounded to an excellent approximation by a parallel surface to the Gyroid, a three-periodic minimal surface with cubic crystallographic symmetry I4132, as foreshadowed by Stavenga and Michielson. The scale of the structure is commensurate with the wavelength of visible light, with an edge of the conventional cubic unit cell of the parallel-Gyroid of approximately 310 nm. The genesis of this structure is discussed, and we suggest it affords a remarkable example of templating of a chiral material via soft matter, analogous to the formation of mesoporous silica via surfactant assemblies in solution. In the butterfly, the templating is achieved by the lipid-protein membranes within the smooth endoplasmic reticulum (while it remains in the chrysalis), that likely form cubic membranes, folded according to the form of the Gyroid. The subsequent formation of the chiral hard chitin framework is suggested to be driven by the gradual polymerisation of the chitin precursors, whose inherent chiral assembly in solution (during growth) promotes the formation of a single enantiomer.

Non-viral vectors in cystic fibrosis gene therapy: recent developments and future prospects.

Gene therapy has been proposed for a wide range of human diseases but few have received the level of attention over such a prolonged period as cystic fibrosis (CF) with over 20 clinical studies undertaken. Following a 10-year interval, clinical trials of an aerosolisable non-viral gene transfer agent have recently been initiated by researchers in the United Kingdom. Here we review the rationale and requirements for effective gene therapy for CF lung disease. The previous non-viral gene therapy trials are discussed and the prospects for the current leading non-viral formulations for CF gene therapy are considered. Factors affecting the selection and design of the plasmid DNA molecule, likely to be of central importance to clinical efficacy, are reviewed and we describe the potential merits of the formulation that has been selected for the forthcoming UK trials.

Three-dimensional Euclidean nets from two-dimensional hyperbolic tilings: kaleidoscopic examples.

We present a method for geometric construction of periodic three-dimensional Euclidean nets by projecting two-dimensional hyperbolic tilings onto a family of triply periodic minimal surfaces (TPMSs). Our techniques extend the combinatorial tiling theory of Dress, Huson & Delgado-Friedrichs to enumerate simple reticulations of these TPMSs. We include a taxonomy of all networks arising from kaleidoscopic hyperbolic tilings with up to two distinct tile types (and their duals, with two distinct vertices), mapped to three related TPMSs, namely Schwarz's primitive (P) and diamond (D) surfaces, and Schoen's gyroid (G).

Progress and prospects: the design and production of plasmid vectors.

Plasmid DNA (pDNA) expression vectors are fundamental to all forms of non-viral gene transfer. In this review, we discuss principles of pDNA design and production including the impact of bacterially derived sequences on transgene expression and minicircle approaches to minimize their effects. The impact of inclusion of DNA elements such as scaffold matrix attachment regions (S/MARs), transcription factor (TF)-binding sites and tissue-specific promoters are described. The benefits of eliminating CG dinucleotides (CpGs) from the pDNA are also considered.

Using saline solutions for ACE washouts.

We had found that twice-normal saline (2NS) antegrade continence enema (ACE) lavages were better than with normal saline (NS) but caused unpleasant symptoms. We therefore undertook a double-blind crossover study comparing water, NS and 2NS in four children. NS produced no disturbances, but water caused a transient fall in plasma osmolality of 7.3 mosmol/kg at 20 min, and falls in urine sodium and osmolality. With 2NS, the plasma sodium rose by 2.5 mmol/l, the plasma proteins rose by 2.3 g/l and the lavage fluid sodium fell, suggesting that about 10 ml/kg of plasma water had moved into the colonic lumen, and two subjects became thirsty. Five other children did home testing. Their home-produced saline was too concentrated and varied widely, and they found that 30 ml/kg of NS produced the same washout result as 20 ml/kg of 2NS. Carefully made-up NS should be used for lavage, increasing volumes if necessary.

Sendai virus-mediated CFTR gene transfer to the airway epithelium.

The potential for gene therapy to be an effective treatment for cystic fibrosis has been hampered by the limited gene transfer efficiency of current vectors. We have shown that recombinant Sendai virus (SeV) is highly efficient in mediating gene transfer to differentiated airway epithelial cells, because of its capacity to overcome the intra- and extracellular barriers known to limit gene delivery. Here, we have identified a novel method to allow the cystic fibrosis transmembrane conductance regulator (CFTR) cDNA sequence to be inserted within SeV (SeV-CFTR). Following in vitro transduction with SeV-CFTR, a chloride-selective current was observed using whole-cell and single-channel patch-clamp techniques. SeV-CFTR administration to the nasal epithelium of cystic fibrosis (CF) mice (Cftr(G551D) and Cftr(tm1Unc)TgN(FABPCFTR)#Jaw mice) led to partial correction of the CF chloride transport defect. In addition, when compared to a SeV control vector, a higher degree of inflammation and epithelial damage was found in the nasal epithelium of mice treated with SeV-CFTR. Second-generation transmission-incompetent F-deleted SeV-CFTR led to similar correction of the CF chloride transport defect in vivo as first-generation transmission-competent vectors. Further modifications to the vector or the host may make it easier to translate these studies into clinical trials of cystic fibrosis.

Squamous cell carcinoma of the vulva with bulky positive groin nodes-nodal debulking versus full groin dissection prior to radiation therapy.

Patients with clinical palpable involved groin lymph nodes and squamous cell cancer of the vulva are frequently treated by a full inguinal-femoral lymph node dissection followed by adjuvant radiotherapy to the groins and pelvis. Theoretically, less radical surgery for the groin such as nodal debulking, where only the macroscopically involved nodes are resected, allowing radiotherapy to treat any remaining microscopic disease may potentially decrease morbidity without compromising survival The objective of this retrospective study was to compare the groin recurrence rate and survival (disease specific and overall survival) of patients with clinically involved groin nodes and squamous cell carcinoma of the vulva treated either by a full inguino-femoral lymphadenectomy or by a nodal debulking followed by radiotherapy. Forty patients from three separate databases who met these criteria were identified. Patients were treated either by a full inguino-femoral lymphadenectomy or by a debulking of the clinically involved inguinal lymph nodes. All patients received adjuvant radiotherapy to the groins. In these two groups, there was no difference in groin recurrence rate expressed as groin recurrence-free survival (P= 0.247). In a univariate analysis, both overall and disease-free survival were better in the group of patients treated by nodal debulking. However, in a multivariate analysis, other variables such as extracapsular growth were independent predictors for survival while the method of surgical dissection for the groin had no independent significant impact on survival.

The training environment of junior anaesthetic registrars learning epidural labour analgesia in Australian teaching hospitals.

Junior anaesthetic registrars perform epidural labour analgesia in many Australian hospitals, however data evaluating training and outcomes are scarce. We aimed to describe and evaluate training practices and environments provided for registrars who learn epidural labour analgesia in their first year of training. Twenty-nine registrars audited their epidurals, participated in semi-structured interviews and completed surveys for six months. The median (inter-quartile range) number of epidurals performed by each registrar was 17 (15-25). Fifty percent performed less than 20. Among 216 audited cases, complications were reported in 19% (dural puncture in 1.4%) and technical difficulties in 16%. Direct supervision was provided for a median (range) of 2.5 (6) epidurals per registrar and for a significantly higher proportion of epidurals performed in tertiary hospitals compared with district metropolitan and rural hospitals (35%, 6% and 22% respectively; P = 0.001). Registrars felt senior staff had supportive attitudes, however the onus for initiating supervision appeared to be with the registrars and responses to survey items addressing role clarity and access to supervision showed wide variation. Only 33% of registrars agreed that they received adequate training before their first epidural and 67% reported workplace stress. None received formal assessments designed to ensure adequate supervision and competency. These results suggest that current training practices for these trainees are inadequate and could be improved by audit and structured workplace learning and assessment activities. We have demonstrated the potential value of measuring a range of training outcomes and environmental factors and have provided baseline data for future research.

Tangled (up in) cubes.

The 'simplest' entanglements of the graph of edges of the cube are enumerated, forming two-cell {6, 3} (hexagonal mesh) complexes on the genus-one two-dimensional torus. Five chiral pairs of knotted graphs are found. The examples contain non-trivial knotted and/or linked subgraphs [(2, 2), (2, 4) torus links and (3, 2), (4, 3) torus knots].