Over the last two decades, model‐based metabolic pathway optimization tools have been developed for the design of microorganisms to produce desired metabolites. However, few have considered more ...complex cellular systems such as mammalian cells, which requires the use of nonlinear kinetic models to capture the effects of concentration changes and cross‐regulatory interactions. In this study, we develop a new two‐stage pathway optimization framework based on kinetic models that incorporate detailed kinetics and regulation information. In Stage 1, a set of optimization problems are solved to identify and rank the enzymes that contribute the most to achieving the metabolic objective. Stage 2 then determines the optimal enzyme interventions for specified desired numbers of enzyme adjustments. It also incorporates multi‐scenario optimization, which allows the simultaneous consideration of multiple physiological conditions. We apply the proposed framework to find enzyme adjustments that enable a reverse glucose flow in cultured mammalian cells, thereby eliminating the need for glucose feed in the late culture stage and enhancing process robustness. The computational results demonstrate the efficacy of the proposed approach; it not only captures the important regulations and key enzymes for reverse glycolysis but also identifies differences and commonalities in the metabolic requirements for different carbon sources.
This study introduces a new kinetic‐model‐based optimization framework for pathway optimization in metabolic engineering.t The proposed two‐stage framework is applied to find optimal enzyme adjustments in energy metabolism that enable a reverse glucose flow in cultured mammalian cells. The computational results demonstrate the efficacy of the proposed approach; it captures the important regulations and key enzymes for reverse glycolysis and identifies differences and commonalities in the metabolic requirements for different carbon sources.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective: Most trainees begin learning robotic minimally invasive surgery by performing inanimate practice tasks with clinical robots such as the Intuitive Surgical da Vinci. Expert surgeons are ...commonly asked to evaluate these performances using standardized five-point rating scales, but doing such ratings is time consuming, tedious, and somewhat subjective. This paper presents an automatic skill evaluation system that analyzes only the contact force with the task materials, the broad-bandwidth accelerations of the robotic instruments and camera, and the task completion time. Methods: We recruited N = 38 participants of varying skill in robotic surgery to perform three trials of peg transfer with a da Vinci Standard robot instrumented with our Smart Task Board. After calibration, three individuals rated these trials on five domains of the Global Evaluative Assessment of Robotic Skill (GEARS) structured assessment tool, providing ground-truth labels for regression and classification machine learning algorithms that predict GEARS scores based on the recorded force, acceleration, and time signals. Results: Both machine learning approaches produced scores on the reserved testing sets that were in good to excellent agreement with the human raters, even when the force information was not considered. Furthermore, regression predicted GEARS scores more accurately and efficiently than classification. Conclusion: A surgeon's skill at robotic peg transfer can be reliably rated via regression using features gathered from force, acceleration, and time sensors external to the robot. Significance: We expect improved trainee learning as a result of providing these automatic skill ratings during inanimate task practice on a surgical robot.
Including preprints in rapid reviews has implications for the rapid review process and review teams should have clear protocol regarding the selection and coverage of bibliographic databases, ...indication within reviews where an included study is a preprint and prespecifying any sensitivity analysis (quantitative or narrative) to assess the impact of inclusion of preprints on the overall results and conclusions. There has been a proliferation of scientific literature in basic science, clinical medicine and public health disseminated through traditional peer review and increasingly, due to the urgent need for information, shared on preprint servers 1,2. While the rapid sharing of research findings may be invaluable, concerns have been raised about circulating preprint versions of articles before they have been through peer review quality assurance processes, particularly in disciplines like medicine, where flawed research could lead to risks to patient safety 16. While preprints may potentially decrease publication bias, they may also increase it through publication of small positive studies, they may influence media discourse, and a lack of awareness of the difference between preprints and published articles may lead to inaccurate preprints being shared as authoritative 17,18.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The posterior orbit is a confined space, harbouring neurovascular structures, frequently distorted by tumours. Image-guided navigation (IGN) has the potential to allow accurate localisation of these ...lesions and structures, reducing collateral damage whilst achieving surgical objectives.
We assessed the feasibility, effectiveness and safety of using an electromagnetic IGN for posterior orbital tumour surgery via a comparative cohort study. Outcomes from cases performed with IGN were compared with a retrospective cohort of similar cases performed without IGN, presenting a descriptive and statistical comparative analysis.
Both groups were similar in mean age, gender and tumour characteristics. IGN set-up and registration were consistently achieved without significant workflow disruption. In the IGN group, fewer lateral orbitotomies (6.7% IGN, 46% non-IGN), and more transcutaneous lid and transconjunctival incisions (93% IGN, 53% non-IGN) were performed (
= .009). The surgical objective was achieved in 100% of IGN cases, with no need for revision surgery (vs 23% revision surgery in non-IGN,
= .005). There was no statistically significant difference in surgical complications.
The use of IGN was feasible and integrated into the orbital surgery workflow to achieve surgical objectives more consistently and allowed the use of minimal access approaches. Future multicentre comparative studies are needed to explore the potential of this technology further.
•In vivo assessment of biomimetic tri-layered scaffolds seeded with rapidly isolated chondrocyte/stromal cell co-cultures.•Biomimetic scaffold-mediated repair of osteochondral defects demonstrated in ...cell-seeded and cell-free groups.•No clear benefit from seeding scaffolds with chondrocyte/stromal cell co-cultures.•Cell-free tri-layered scaffolds represent a more prudent clinical approach.
Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs. In this study, we hypothesized that seeding biomimetic tri-layered scaffolds, with proven regenerative potential, with chondrocyte/infrapatellar fat pad stromal cell co-cultures would improve their regenerative capacity compared to scaffolds implanted cell-free. Rapid cell isolation techniques, without the requirement for long term in vitro culture, were utilised to achieve co-cultures of chondrocytes and stromal cells and thus overcome the limitations of existing cell-based techniques. Cell-free and cell-seeded scaffolds were implanted in osteochondral defects, created within the femoral condyle and trochlear ridge, in a translational large animal goat model. While analysis showed trends towards delayed subchondral bone healing in the cell-seeded scaffold group, by the 12 month timepoint the cell-free and cell-seeded groups yield cartilage and bone tissue with comparable quality and quantity. The results of the study reinforce the potential of the biomimetic tri-layered scaffold to repair joint defects but failed to demonstrate a clear benefit from the addition of the CC/FPMSC co-culture to this scaffold. Taking into consideration the additional cost and complexity associated with the cell-seeded scaffold approach, this study demonstrates that the treatment of osteochondral defects using cell-free tri-layered scaffolds may represent a more prudent clinical approach.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
In 2019, a migrant camp on the Greek island of Samos designed for 650 people was home to a growing population of over 5500. We aimed to quantitatively describe living conditions and health ...needs in the camp.
Methods
A questionnaire was designed with reference to international humanitarian standards, following a consultative process with the asylum-seeker population. Domains assessed included demographics, living conditions, safety/vulnerability, and health. The questionnaire was piloted and then conducted in June 2019 on a sample of asylum seekers.
Results
Five hundred participants, predominantly from Afghanistan and the Democratic Republic of Congo (DRC). Of these, 79.4% lived in tents. Respondents cared for a total of 570 children; 20.6% of women were pregnant, 35.4% had experienced violence, 83% psychological distress, 71% skin disease, 66% diarrhoea and vomiting, and 64% respiratory disease. Accommodation, sanitation, and nutrition fell below internationally recognised standards, and poor access to water was significantly associated (
p
< 0.001) with respiratory disease, diarrhoea and vomiting, skin disease ,and psychological distress.
Conclusions
Living conditions in the Samos camp fall below basic humanitarian standards and are associated with poor health status. Further research is imperative to analyse and monitor the diverse, varying needs of asylum-seekers and inform policies to improve conditions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The quadratus lumborum (QL) block facilitates the administration of anaesthesia to the anterior abdominal wall. The use of ultrasound (US) improves the accuracy of the QL block and reduces the risk ...of adverse events. Electromyography (EMG) in combination with US for muscle plane blocks has not been described previously. We postulated that the addition of EMG-guided needle positioning might assist the execution of this block. This case report describes the first use of combined needle EMG and US to carry out a QL block performed for postoperative analgesia following an open appendicectomy.
In response to ESA Voyage 2050 announcement of opportunity, we propose an ambitious L-class mission to explore one of the most exciting bodies in the Solar System, Saturn largest moon Titan. Titan, a ..."world with two oceans", is an organic-rich body with interior-surface-atmosphere interactions that are comparable in complexity to the Earth. Titan is also one of the few places in the Solar System with habitability potential. Titan remarkable nature was only partly revealed by the Cassini-Huygens mission and still holds mysteries requiring a complete exploration using a variety of vehicles and instruments. The proposed mission concept POSEIDON (Titan POlar Scout/orbitEr and In situ lake lander DrONe explorer) would perform joint orbital and in situ investigations of Titan. It is designed to build on and exceed the scope and scientific/technological accomplishments of Cassini-Huygens, exploring Titan in ways that were not previously possible, in particular through full close-up and in situ coverage over long periods of time. In the proposed mission architecture, POSEIDON consists of two major elements: a spacecraft with a large set of instruments that would orbit Titan, preferably in a low-eccentricity polar orbit, and a suite of in situ investigation components, i.e. a lake lander, a "heavy" drone (possibly amphibious) and/or a fleet of mini-drones, dedicated to the exploration of the polar regions. The ideal arrival time at Titan would be slightly before the next northern Spring equinox (2039), as equinoxes are the most active periods to monitor still largely unknown atmospheric and surface seasonal changes. The exploration of Titan northern latitudes with an orbiter and in situ element(s) would be highly complementary with the upcoming NASA New Frontiers Dragonfly mission that will provide in situ exploration of Titan equatorial regions in the mid-2030s.
Abstract Objectives Identifying clinical prediction rules (CPRs) for primary care from electronic databases is difficult. This study aims to identify a search filter to optimize retrieval of these to ...establish a register of CPRs for the Cochrane Primary Health Care field. Study Design and Setting Thirty primary care journals were manually searched for CPRs. This was compared with electronic search filters using alternative methodologies: (1) textword searching; (2) proximity searching; (3) inclusion terms using specific phrases and truncation; (4) exclusion terms; and (5) combinations of methodologies. Results We manually searched 6,344 articles, revealing 41 CPRs. Across the 45 search filters, sensitivities ranged from 12% to 98%, whereas specificities ranged from 43% to 100%. There was generally a trade-off between the sensitivity and specificity of each filter (i.e., the number of CPRs and total number of articles retrieved). Combining textword searching with the inclusion terms (using specific phrases) resulted in the highest sensitivity (98%) but lower specificity (59%) than other methods. The associated precision (2%) and accuracy (60%) were also low. Conclusion The novel use of combining textword searching with inclusion terms was considered the most appropriate for updating a register of primary care CPRs where sensitivity has to be optimized.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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