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This position paper establishes a way towards a post-anthropocentric understanding of serendipity, or the happy accident, in making processes across art, craft and design. Throwing into question hylomorphic attempts to understand the application of the maker’s know-how, which devalues the enabling capabilities of the ‘happy accident’, this position paper sets a course towards a post-anthropocentric model of making. Exploring the ineffability of materials and other events or circumstances that lie outside of purposeful affordances diffracts the focus from purposeful human agency. Instead, re-understanding the maker’s process and knowledge as a transcendent intra-action between flows of material and cognition opens up space for a more subtle and comprehensive investigation into the complexity of human and non-human intra-action, which shapes the maker and the made in a reciprocal process.

Background: Accurate camera and hand-eye calibration are essential to ensure high-quality results in image-guided surgery applications. The process must also be able to be undertaken by a nonexpert user in a surgical setting. Purpose: This work seeks to identify a suitable method for tracked stereo laparoscope calibration within theater. Methods: A custom calibration rig, to enable rapid calibration in a surgical setting, was designed. The rig was compared against freehand calibration. Stereo reprojection, stereo reconstruction, tracked stereo reprojection, and tracked stereo reconstruction error metrics were used to evaluate calibration quality. Results: Use of the calibration rig reduced mean errors: reprojection (1.47 mm [SD 0.13] vs. 3.14 mm [SD 2.11], p-value 1e−8), reconstruction (1.37 px [SD 0.10] vs. 10.10 px [SD 4.54], p-value 6e−7), and tracked reconstruction (1.38 mm [SD 0.10] vs. 12.64 mm [SD 4.34], p-value 1e−6) compared with freehand calibration. The use of a ChArUco pattern yielded slightly lower reprojection errors, while a dot grid produced lower reconstruction errors and was more robust under strong global illumination. Conclusion: The use of the calibration rig results in a statistically significant decrease in calibration error metrics, versus freehand calibration, and represents the preferred approach for use in the operating theater.

Plants are a vital component of human life on Earth; they provide us with food and essential nutrients as well as the oxygen we breathe. However, the science education community struggles to find ways to make plant processes less abstract and more understandable for learners. In this article we demonstrate how we make plant processes more understandable for learners by observing the behaviors of a specific plant structure, a stoma, which is a microscopic opening that plays a role in the movement of matter into and out of a plant. Recent research across plant-related science fields centers on plant stomata because they protect plants from various environmental strains, including attacks from pathogens. Translating this research into science classroom instruction has not occurred extensively. A key impediment is that few common methods to make stomata visible or demonstrate their dynamic nature to learners are available. The activities we share here make stomata visible utilizing a specific plant, Tradescantia zebrina, and common laboratory equipment. In the first activity, we share how to demonstrate stomata closing and opening by manipulating a combination of these environmental factors. In the second activity, we describe how to create a visual simulation of stomata response to attacks from microorganisms.

This report describes a piece of participatory research undertaken in 2022 as part of the UK-aid funded Disability Inclusive Development programme. Under this programme, Task Order 27 developed a model of disability-inclusive education in selected schools in Kaduna State, Nigeria and the authors of this report worked on the development of a tool to measure how children with disabilities (and their parents) perceive their inclusion in school and society, as well as their wellbeing. The tool was developed in a way which was informed by what children themselves see as important. It was also designed to show changes in experiences and perceptions overtime through repeated use of the tool over a one-year period. This report describes Phase 1 which covers the process of planning, designing and testing the tool.

Purpose Image-guided surgery (IGS) is an integral part of modern neuro-oncology surgery. Navigated ultrasound provides the surgeon with reconstructed views of ultrasound data, but no commercial system presently permits its integration with other essential non-imaging-based intraoperative monitoring modalities such as intraoperative neuromonitoring. Such a system would be particularly useful in skull base neurosurgery. Methods We established functional and technical requirements of an integrated multi-modality IGS system tailored for skull base surgery with the ability to incorporate: (1) preoperative MRI data and associated 3D volume reconstructions, (2) real-time intraoperative neurophysiological data and (3) live reconstructed 3D ultrasound. We created an open-source software platform to integrate with readily available commercial hardware. We tested the accuracy of the system’s ultrasound navigation and reconstruction using a polyvinyl alcohol phantom model and simulated the use of the complete navigation system in a clinical operating room using a patient-specific phantom model. Results Experimental validation of the system’s navigated ultrasound component demonstrated accuracy of $$ < 4.5 mm and a frame rate of 25 frames per second. Clinical simulation confirmed that system assembly was straightforward, could be achieved in a clinically acceptable time of $$ < 15 min and performed with a clinically acceptable level of accuracy. Conclusion We present an integrated open-source research platform for multi-modality IGS. The present prototype system was tailored for neurosurgery and met all minimum design requirements focused on skull base surgery. Future work aims to optimise the system further by addressing the remaining target requirements.

There is an urgent need for new treatments for visceral leishmaniasis (VL), a parasitic infection which impacts heavily large areas of East Africa, Asia, and South America. We previously reported on the discovery of GSK3494245/DDD01305143 (1) as a preclinical candidate for VL and, herein, we report on the medicinal chemistry program that led to its identification. A hit from a phenotypic screen was optimized to give a compound with in vivo efficacy, which was hampered by poor solubility and genotoxicity. The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chemistry design, in silico profiling, and subsequent synthesis was utilized, leading to the preclinical candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series' structure-activity relationships.

Elizabeth James,1 Holly Trautman,1 Stephen Thompson,2 Rinat Ribalov,3 Azhar Choudhry4 1Aventine Consulting LLC, Marblehead, MA, USA; 2Global Health Economics and Outcomes Research, Teva Branded Pharmaceutical Products R&D, Inc, Parsippany, NJ, USA; 3Global Health Economics and Outcomes Research, Teva Pharmaceutical Industries Ltd, Petah Tikva, Israel; 4Medical Affairs, Teva Branded Pharmaceutical Products R&D, Inc, Parsippany, NJ, USACorrespondence: Elizabeth James Tel +1 425 290 2148Email elizabeth@aventine-consulting.comBackground: Bendamustine hydrochloride (BND HCl) is indicated for first-line treatment of chronic lymphocytic leukemia (CLL) and rituximab-refractory indolent non-Hodgkin lymphoma (iNHL). There are two ready-to-dilute (RTD) formulations of BND HCl on the US market: a large-volume, long-duration infusion (BND-L) and a small-volume, short-duration infusion (BND-S). It is estimated that the shorter duration infusion could result in cost savings to infusion facilities.Objective: Estimate the one-year budget impact between BND-S and BND-L for use in the treatment of CLL and iNHL when all current BND-L utilization is replaced with BND-S, from the US infusion facility perspective.Methods: An illustrative budget impact model estimated the change in costs associated with a projected increase from 50% to 100% market share for BND-S. The model included CLL and iNHL patient populations. Budgetary costs reflected facility expenditures on drug acquisition and administration based on recommended dosing for BND-S and BND-L. The base-case model assumptions and inputs were derived from scientific literature and publicly available resources. The total budget impact was calculated annually, along with the differences in per patient cost; one-way sensitivity analyses were conducted.Results: Per-patient savings with BND-S use after the utilization shift were estimated at $2812.24 for CLL and $4769.01 for iNHL. Across both indications, the total annual incremental savings after the utilization shift were estimated at $452,209 for 250 CLL and iNHL patients in a 10,000-patient infusion facility, resulting in cost savings of $150.74 per BND HCI patient per month and $1808.84 per BND HCI patient per year. The model was sensitive to changes in proportion of patients receiving BND HCI infusions for CLL and iNHL, patient body surface area, and BND-S wholesale acquisition cost.Conclusion: This analysis estimated over $450,000 in annual savings for a 10,000-patient chemotherapy infusion facility following a utilization shift from 50% use of each RTD product to 100% use of BND-S in CLL and iNHL patients, driven by lower acquisition costs for BND-S and lower administration labor costs associated with rapid infusion.Keywords: chronic lymphocytic leukemia, indolent non-Hodgkin lymphoma, budget impact, bendamustine, infusion

The report describes how IDS organised and ran a series of action learning groups with jobseekers and employers involved with the FCDO-funded Inclusion Works programme. Action learning groups are a participatory way of learning over time about the participants’ experiences of the programme and their wider perceptions of the world of work and moves towards more inclusive practice generally. The groups were held in the four programme countries: Bangladesh, Kenya, Nigeria and Uganda. The report includes key findings and reflections from the groups, the local facilitators and the IDS team.

Background: Suspension training systems, which use body weight resistance under unstable conditions, may be effective for muscle strengthening in persons with scapular dyskinesis or subacromial impingement syndrome. Hypothesis: Greater arm, scapular, and trunk muscle recruitment will occur during horizontal abduction row exercises. Study Design: Descriptive laboratory study. Level of Evidence: Level 5. Methods: Surface electromyography data were collected from 28 participants (14 men, 14 women). A total of 13 right-sided muscles were studied at a sampling frequency of 1000 Hz. Maximal voluntary isometric contractions (MVICs) were established. Participants completed 3 repetitions per exercise in random order. We compared muscle recruitment during 3 rowing exercises: low row, high row, and horizontal abduction row. Data were compared with repeated-measures analyses of variance and post hoc Bonferroni corrections. Results: For high row and horizontal abduction row conditions, the upper, middle, and lower trapezius and posterior deltoid demonstrated >60% MVIC magnitudes of recruitment, and the upper erector spinae demonstrated 40% to 60% MVIC magnitudes of recruitment, respectively. In contrast, in the low row exercise, 40% to 60% MVIC magnitudes of recruitment were observed only in the middle trapezius, latissimus dorsi, and posterior deltoid. Conclusion: With the suspension system, high row and horizontal abduction row exercises promote muscle strengthening (>50% MVIC) in the upper, middle, and lower fibers of the trapezius, posterior deltoid, and upper erector spinae. Clinical Relevance: Rowing exercises performed with suspension straps may be recommended for muscle strengthening in patients with scapular dyskinesis and subacromial impingement syndrome as well as for healthy persons in need of enhanced scapular muscle performance.

Visceral leishmaniasis (VL) is a parasitic infection that results in approximately 26 000–65 000 deaths annually. The available treatments are hampered by issues such as toxicity, variable efficacy...

Purpose This paper introduces the SciKit-Surgery libraries, designed to enable rapid development of clinical applications for image-guided interventions. SciKit-Surgery implements a family of compact, orthogonal, libraries accompanied by robust testing, documentation, and quality control. SciKit-Surgery libraries can be rapidly assembled into testable clinical applications and subsequently translated to production software without the need for software reimplementation. The aim is to support translation from single surgeon trials to multicentre trials in under 2 years. Methods At the time of publication, there were 13 SciKit-Surgery libraries provide functionality for visualisation and augmented reality in surgery, together with hardware interfaces for video, tracking, and ultrasound sources. The libraries are stand-alone, open source, and provide Python interfaces. This design approach enables fast development of robust applications and subsequent translation. The paper compares the libraries with existing platforms and uses two example applications to show how SciKit-Surgery libraries can be used in practice. Results Using the number of lines of code and the occurrence of cross-dependencies as proxy measurements of code complexity, two example applications using SciKit-Surgery libraries are analysed. The SciKit-Surgery libraries demonstrate ability to support rapid development of testable clinical applications. By maintaining stricter orthogonality between libraries, the number, and complexity of dependencies can be reduced. The SciKit-Surgery libraries also demonstrate the potential to support wider dissemination of novel research. Conclusion The SciKit-Surgery libraries utilise the modularity of the Python language and the standard data types of the NumPy package to provide an easy-to-use, well-tested, and extensible set of tools for the development of applications for image-guided interventions. The example application built on SciKit-Surgery has a simpler dependency structure than the same application built using a monolithic platform, making ongoing clinical translation more feasible.

Telecollaboration involves the teleportation of a remote collaborator to another real-world environment where their partner is located. The fidelity of the environment plays an important role for allowing corresponding spatial references in remote collaboration. We present a novel asymmetric platform, Augmented Virtual Teleportation (AVT), which provides high-fidelity telepresence of a remote VR user ( VR-Traveler ) into a real-world collaboration space to interact with a local AR user ( AR-Host ). AVT uses a 360° video camera (360-camera) that captures and live-streams the omni-directional scenes over a network. The remote VR-Traveler watching the video in a VR headset experiences live presence and co-presence in the real-world collaboration space. The VR-Traveler's movements are captured and transmitted to a 3D avatar overlaid onto the 360-camera which can be seen in the AR-Host's display. The visual and audio cues for each collaborator are synchronized in the Mixed Reality Collaboration space (MRC-space), where they can interactively edit virtual objects and collaborate in the real environment using the real objects as a reference. High fidelity, real-time rendering of virtual objects and seamless blending into the real scene allows for unique mixed reality use-case scenarios. Our working prototype has been tested with a user study to evaluate spatial presence, co-presence, and user satisfaction during telecollaboration. Possible applications of AVT are identified and proposed to guide future usage.

Soluble forms of aggregated tau misfolded protein, generally termed oligomers, are considered to be the most toxic species of the different assembly states that are the pathological components of neurodegenerative disorders. Therefore, a critical biomedical need exists for imaging probes that can identify and quantify them. We have designed and synthesized a novel fluorescent probe, pTP-TFE for which binding and selectivity profiles towards aggregated tau and Aβ proteins were assessed. Our results have shown pTP-TFE to be selective for early forms of soluble tau aggregates, with high affinity of dissociation constants (Kd) = 66 nM, and tenfold selectivity over mature tau fibrils. Furthermore, we found that pTP-TFE is selective for tau over Aβ aggregates and had good cell permeability. This selectivity of pTP-TFE towards early forms of aggregated tau protein ex vivo was also supported with studies on human brain tissue containing tau and Aβ pathology. To the best of our knowledge, this is the first fluorescent molecule to be reported to have this form of selectivity profile, which suggests that pTP-TFE is a unique probe candidate for imaging-based detection of early stages of Alzheimer's disease and other tauopathies., pTP-TFE imaging probe can distinguish soluble tau aggregated proteins from other aggregated proteins enabling earlier detection of neurodegenerative diseases.