SCOPE Process: Fostering Students\u27 Design Outcome Effectiveness

The purpose of this article is to help Technology and Engineering Educators scaffold engineering design and problem-solving experiences so that students taking technology and engineering courses will develop an improved ability to design. Technology and Engineering Education seems to increasingly focus on problem-solving, design, and engineering. Technology and Engineering Education is not the only discipline with this focus. The fact that both Science and Technology and Engineering Education are similarly focused on the teaching and learning of engineering begs the question of what separates technology and engineering educators from science educators in the teaching of engineering? Lewis (2004) cautioned that the introduction of engineering signaled the discipline turning away from more practical, blue-collar knowledge, towards white-collar academic traditions. Lewis (2004) highlighted John Dewey\u27s argument that manual training was a gateway for students to integrate math and science

Automatic motion compensation for structured illumination endomicroscopy using a flexible fiber bundle

Significance: Confocal laser scanning enables optical sectioning in clinical fiber bundle endomicroscopes, but lower-cost, simplified endomicroscopes use widefield incoherent illumination instead. Optical sectioning can be introduced in these simple systems using structured illumination microscopy (SIM), a multiframe digital subtraction process. However, SIM results in artifacts when the probe is in motion, making the technique difficult to use in vivo and preventing the use of mosaicking to synthesize a larger effective field of view (FOV). Aim: We report and validate an automatic motion compensation technique to overcome motion artifacts and allow generation of mosaics in SIM endomicroscopy. Approach: Motion compensation is achieved using image registration and real-time pattern orientation correction via a digital micromirror device. We quantify the similarity of moving probe reconstructions to those acquired with a stationary probe using the relative mean of the absolute differences (MAD). We further demonstrate mosaicking with a moving probe in mechanical and freehand operation. Results: Reconstructed SIM images show an improvement in the MAD from 0.85 to 0.13 for lens paper and from 0.27 to 0.12 for bovine tissue. Mosaics also show vastly reduced artifacts. Conclusion: The reduction in motion artifacts in individual SIM reconstructions leads to mosaics that more faithfully represent the morphology of tissue, giving clinicians a larger effective FOV than the probe itself can provide

Impact of Covid-19 on clinical care and lived experience of systemic sclerosis:An international survey from EURORDIS-Rare Diseases Europe

INTRODUCTION: Outcomes related to Covid-19 in systemic sclerosis patients could be influenced by internal organ involvement and/or immunosuppressive treatment, leading to efforts to shield patients from Covid-19 transmission. We examined the impact of Covid-19 on the lived experience of systemic sclerosis with regards to other aspects of daily living including occupation and emotional well-being. METHOD: Individuals with systemic sclerosis or relatives/carers participated in an online survey, disseminated through international patient associations and social media pages, designed to examine the impact of Covid-19 on living with a rare disease. RESULTS: Responses from 121 individuals (98% were patients with systemic sclerosis) from 14 countries were evaluable. Covid-19 was considered a probable/definite personal threat (93%) or threat for the individual they care for (100%). Approximately two-thirds of responders reported either cancellation or postponement/delay to appointments, diagnostic tests, medical therapies at home (e.g. infusions), surgery or transplant, psychiatry follow-up or rehabilitation services. Twenty-six percent reported at least one systemic sclerosis medicine/treatment had been unavailable, and 6% had to either stop taking usual medications or use an alternative. Most reported online consultations/telemedicine via phone (88%) and online (96%) as being ‘fairly’ or ‘very’ useful. Respondents reported tensions among family members (45%) and difficulty overcoming problems (48%). Restrictions on movement left around two-thirds feeling isolated (61%), unhappy and/or depressed (64%), although the majority (85%) reported a strengthening of the family unit. CONCLUSION: Covid-19 has resulted in significant impact on the clinical-care and emotional well-being of systemic sclerosis patients. Changes to clinical care delivery have been well-received by patients including telemedicine consultations

The Clinical Frailty Scale can be used retrospectively to assess the frailty of patients with hip fracture:a validation study

PURPOSE: Frailty is a common clinical syndrome affecting hip fracture patients. Recognising and accurately assessing frailty status is important in clinical and research settings. The Rockwood Clinical Frailty Scale (CFS) is a commonly used instrument and demonstrates a strong correlation with mortality and length of hospital admission following hip fracture. What is not understood, however, is the validity of retrospectively assigned CFS scores in hip fracture patients. The aim of this study was to assess the validity of retrospective non-orthogeriatrician assigned CFS scores in hip fracture patients. METHODS: Hip fracture patients from a single major trauma centre were assessed and CFS scores were assigned prospectively by non-orthogeriatric clinicians (n = 57). A subset of these patients were also assigned a prospective CFS score by a specialist orthogeriatrician (n = 27). Two separate blinded observers (non-orthogeriatric clinicians) assigned CFS scores retrospectively using electronic patient records alone. Agreement and precision was examined using the Bland–Altman plot, accuracy was assessed using R(2) statistic and inter-rater reliability was assessed using quadratic weighted Cohen’s kappa. RESULTS: Seventy percent of the cohort were female with an average age of 83. Agreement was high between prospective non-orthogeriatrician assigned CFS scores and retrospective non-orthogeriatrician assigned CFS scores, with a low bias (0.046) and good accuracy (R(2) = 73%). Good agreement was also seen in comparisons between prospective orthogeriatrician assigned CFS scores versus retrospective non-orthogeriatrician assigned scores, with a low bias (0.23) and good accuracy (R(2) = 78%). Good inter-rater reliability was seen between blinded observers with a quadratic weighted Cohen’s kappa of 0.76. CONCLUSIONS: Retrospective CFS scores assigned by non-orthogeriatricians are a valid means of assessing frailty status in hip fracture patients. However, our results suggest a tendency for non-orthogeriatricians to marginally overestimate frailty status when assigning CFS scores retrospectively. LEVEL OF EVIDENCE: 3

Screen Time and Executive Function in Toddlerhood: A Longitudinal Study.

Technology is pervasive in homes with young children. Emerging evidence that electronic screen-based media use has adverse effects on executive functions may help explain negative relations between media use and early academic skills. However, longitudinal investigations are needed to test this idea. In a sample of 193 British toddlers tracked from age 2 to 3 years, we test concurrent and predictive relations between screen use and children's executive function. We find no concurrent association between screen use and executive function; however, screen time at age 2 is negatively associated with the development of executive functions in toddlerhood from age 2 to 3, controlling for a range of covariates including verbal ability. Implications for parenting, education, and pediatric recommendations are discussed

Cost-effectiveness of initial stress cardiovascular MR, stress SPECT or stress echocardiography as a gate-keeper test, compared with upfront invasive coronary angiography in the investigation and management of patients with stable chest pain: Mid-term outcomes from the CECaT randomised controlled trial

Objectives: To compare outcomes and cost-effectiveness of various initial imaging strategies in the management of stable chest pain in a long-term prospective randomised trial. Setting: Regional cardiothoracic referral centre in the east of England. Participants: 898 patients (69% man) entered the study with 869 alive at 2 years of follow-up. Patients were included if they presented for assessment of stable chest pain with a positive exercise test and no prior history of ischaemic heart disease. Exclusion criteria were recent infarction, unstable symptoms or any contraindication to stress MRI. Primary outcome measures: The primary outcomes of this follow-up study were survival up to a minimum of 2 years post-treatment, quality-adjusted survival and cost-utility of each strategy. Results: 898 patients were randomised. Compared with angiography, mortality was marginally higher in the groups randomised to cardiac MR (HR 2.6, 95% CI 1.1 to 6.2), but similar in the single photon emission CT-methoxyisobutylisonitrile (SPECT-MIBI; HR 1.0, 95% CI 0.4 to 2.9) and ECHO groups (HR 1.6, 95% CI 0.6 to 4.0). Although SPECT-MIBI was marginally superior to other non-invasive tests there were no other significant differences between the groups in mortality, quality-adjusted survival or costs. Conclusions: Non-invasive cardiac imaging can be used safely as the initial diagnostic test to diagnose coronary artery disease without adverse effects on patient outcomes or increased costs, relative to angiography. These results should be interpreted in the context of recent advances in imaging technology. Trial registration: ISRCTN 47108462, UKCRN 3696

Functional asymmetry in the lysyl-tRNA synthetase explored by molecular dynamics, free energy calculations and experiment

BACKGROUND: Charging of transfer-RNA with cognate amino acid is accomplished by the aminoacyl-tRNA synthetases, and proceeds through an aminoacyl adenylate intermediate. The lysyl-tRNA synthetase has evolved an active site that specifically binds lysine and ATP. Previous molecular dynamics simulations of the heat-inducible Escherichia coli lysyl-tRNA synthetase, LysU, have revealed differences in the binding of ATP and aspects of asymmetry between the nominally equivalent active sites of this dimeric enzyme. The possibility that this asymmetry results in different binding affinities for the ligands is addressed here by a parallel computational and biochemical study. RESULTS: Biochemical experiments employing isothermal calorimetry, steady-state fluorescence and circular dichroism are used to determine the order and stoichiometries of the lysine and nucleotide binding events, and the associated thermodynamic parameters. An ordered mechanism of substrate addition is found, with lysine having to bind prior to the nucleotide in a magnesium dependent process. Two lysines are found to bind per dimer, and trigger a large conformational change. Subsequent nucleotide binding causes little structural rearrangement and crucially only occurs at a single catalytic site, in accord with the simulations. Molecular dynamics based free energy calculations of the ATP binding process are used to determine the binding affinities of each site. Significant differences in ATP binding affinities are observed, with only one active site capable of realizing the experimental binding free energy. Half-of-the-sites models in which the nucleotide is only present at one active site achieve their full binding potential irrespective of the subunit choice. This strongly suggests the involvement of an anti-cooperative mechanism. Pathways for relaying information between the two active sites are proposed. CONCLUSIONS: The asymmetry uncovered here appears to be a common feature of oligomeric aminoacyl-tRNA synthetases, and may play an important functional role. We suggest a manner in which catalytic efficiency could be improved by LysU operating in an alternating sites mechanism

Discovery of active proteins directly from combinatorial randomized protein libraries without display, purification or sequencing:identification of novel zinc finger proteins.

We have successfully linked protein library screening directly with the identification of active proteins, without the need for individual purification, display technologies or physical linkage between the protein and its encoding sequence. By using 'MAX' randomization we have rapidly constructed 60 overlapping gene libraries that encode zinc finger proteins, randomized variously at the three principal DNA-contacting residues. Expression and screening of the libraries against five possible target DNA sequences generated data points covering a potential 40,000 individual interactions. Comparative analysis of the resulting data enabled direct identification of active proteins. Accuracy of this library analysis methodology was confirmed by both in vitro and in vivo analyses of identified proteins to yield novel zinc finger proteins that bind to their target sequences with high affinity, as indicated by low nanomolar apparent dissociation constants