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Nb3Sn conductors are important candidates for high-field magnets for particle accelerators, and they continue to be widely used for many laboratory and NMR magnets. However, the critical current density, Jc, of present Nb3Sn conductors declines swiftly above 12-15T. State-of-the-art Ta- and Ti-doped strands exhibit upper critical field, Hc2, values of 24-26.5T (4.2K) and do not reach the FCC target Jc, which serves as the present stretch target for Nb3Sn development. As recently demonstrated, to meet this goal requires enhanced vortex pinning but an independent and supplementary approach is to significantly enhance Hc2. In this study, we have arc-melted multiple Nb alloys with added Hf, Zr, Ta and Ti and drawn them successfully into monofilament wires to investigate the possibilities of Hc2 enhancement through alloying. Hc2(T) was measured for all samples in fields up to 16T and some up to 31T. We have found that all alloys show good agreement with the standard Werthamer, Helfand, and Hohenberg (WHH) fitting procedure without the need to adjust the paramagnetic limitation parameter (alpha) and spin-orbit scattering parameter (lambda_so). The evaluation of dHc2/dT near Tc, which is proportional to the electronic specific heat coefficient (gamma) and the normal state resistivity (rho_n), allows a better understanding of the induced disorder introduced by alloying in the A15 phase. So far, we have observed that Hf alloying of pure Nb can enhance Hc2(0) by 3-4T to 28T, while adding just 1 at. %Hf or Zr into a Nb4Ta base alloy can raise Hc2(0) to 31T. Very importantly we find that Hf and Zr raise the alloy recrystallization temperature above the usual A15 reaction temperature range of 650{\deg}C-750{\deg}C, thus ensuring denser A15 phase nucleation in the Nb alloy grain boundaries, possibly leading to a more homogeneous A15 phase Sn content and refined A15 grain size. The potential for..., Comment: 16 pages, 11 figures

Colorectal cancer (CRC) poses a major public health challenge, with it being the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide as of 2024. Microsatellite instability-high (MSI-H) CRC and deficient mismatch repair (dMMR) CRC comprise $15\%$ of all CRC and have shown remarkable response to immunotherapy, especially with PD-1 inhibitors. Mathematical models are a promising avenue for treatment optimisation, and we use delay integro-differential equations to model the interactions and dynamics of various cell types, immune checkpoints, damage-associated molecular patterns (DAMPs), and cytokines. We note that many of these species are being modelled deterministically for the first time in cancer, paving the way for a deeper understanding of the complex underlying immune dynamics. We consider two compartments: the tumour site and the tumour-draining lymph node (TDLN), taking into account phenomena such as DC migration, T cell proliferation, acquired resistance to pembrolizumab, and CD8+ T cell exhaustion and reinvigoration. The parameter values and initial conditions for the model are estimated from experimental data, incorporating various pharmacokinetic, bioanalytical, and radiographic studies, as well as deconvolution of bulk RNA-sequencing data from the TCGA COADREAD database. We finally optimise CRC treatment with neoadjuvant pembrolizumab $\unicode{x2014}$ one of the most used PD-1 inhibitors. We maximise treatment efficacy and efficiency in locally advanced MSI-H/dMMR CRC patients whilst accounting for toxicity, and improve upon currently FDA-approved therapeutic regimens for metastatic MSI-H/dMMR CRC. We demonstrate that a single medium-to-high dose of pembrolizumab is sufficient for effective tumour eradication, whilst being efficient, safe and practical., Comment: 102 pages in total with 64 pages for the main body and 38 pages for the supporting information, 3 figures in the main body, 9 tables in the main body, 11 tables in the supporting information. Minor edits have been made

The application of autonomous robotics to close-contact healthcare tasks has a clear role for the future due to its potential to reduce infection risks to staff and improve clinical efficiency. Nasopharyngeal (NP) swab sample collection for diagnosing upper-respiratory illnesses is one type of close contact task that is interesting for robotics due to the dexterity requirements and the unobservability of the nasal cavity. We propose a control system that performs the test using a collaborative manipulator arm with an instrumented end-effector to take visual and force measurements, under the scenario that the patient is unrestrained and the tools are general enough to be applied to other close contact tasks. The system employs a visual servo controller to align the swab with the nostrils. A compliant joint velocity controller inserts the swab along a trajectory optimized through a simulation environment, that also reacts to measured forces applied to the swab. Additional subsystems include a fuzzy logic system for detecting when the swab reaches the nasopharynx and a method for detaching the swab and aborting the procedure if safety criteria is violated. The system is evaluated using a second robotic arm that holds a nasal cavity phantom and simulates the natural head motions that could occur during the procedure. Through extensive experiments, we identify controller configurations capable of effectively performing the NP swab test even with significant head motion, which demonstrates the safety and reliability of the system., Comment: 18 pages, 26 figures. Supplementary files may be found at https://uwaterloo.ca/scholar/pqjlee/supplementary-files-complete-autonomous-robotic-nasopharyngeal-swab-system-evaluation

The nasopharyngeal (NP) swab test is a method for collecting cultures to diagnose for different types of respiratory illnesses, including COVID-19. Delegating this task to robots would be beneficial in terms of reducing infection risks and bolstering the healthcare system, but a critical component of the NP swab test is having the swab aligned properly with the nasal cavity so that it does not cause excessive discomfort or injury by traveling down the wrong passage. Existing research towards robotic NP swabbing typically assumes the patient's head is held within a fixture. This simplifies the alignment problem, but is also dissimilar to clinical scenarios where patients are typically free-standing. Consequently, our work creates a vision-guided pipeline to allow an instrumented robot arm to properly position and orient NP swabs with respect to the nostrils of free-standing patients. The first component of the pipeline is a precomputed joint lookup table to allow the arm to meet the patient's arbitrary position in the designated workspace, while avoiding joint limits. Our pipeline leverages semantic face models from computer vision to estimate the Euclidean pose of the face with respect to a monocular RGB-D camera placed on the end-effector. These estimates are passed into an unscented Kalman filter on manifolds state estimator and a pose based visual servo control loop to move the swab to the designated pose in front of the nostril. Our pipeline was validated with human trials, featuring a cohort of 25 participants. The system is effective, reaching the nostril for 84% of participants, and our statistical analysis did not find significant demographic biases within the cohort., Comment: 12 pages, 13 figures

The nasopharyngeal (NP) swab sample test, commonly used to detect COVID-19 and other respiratory illnesses, involves moving a swab through the nasal cavity to collect samples from the nasopharynx. While typically this is done by human healthcare workers, there is a significant societal interest to enable robots to do this test to reduce exposure to patients and to free up human resources. The task is challenging from the robotics perspective because of the dexterity and safety requirements. While other works have implemented specific hardware solutions, our research differentiates itself by using a ubiquitous rigid robotic arm. This work presents a case study where we investigate the strengths and challenges using compliant control system to accomplish NP swab tests with such a robotic configuration. To accomplish this, we designed a force sensing end-effector that integrates with the proposed torque controlled compliant control loop. We then conducted experiments where the robot inserted NP swabs into a 3D printed nasal cavity phantom. Ultimately, we found that the compliant control system outperformed a basic position controller and shows promise for human use. However, further efforts are needed to ensure the initial alignment with the nostril and to address head motion., Comment: 13 pages, 9 figures. See https://uwaterloo.ca/scholar/pqjlee/collaborative-robot-arm-inserting-nasopharyngeal-swabs-admittance-control for supplementary data

The evolution of synchrotrons towards higher brilliance beams has increased the possible sample-to-detector propagation distances for which the source confusion circle does not lead to geometrical blurring. This makes it possible to push near-field propagation driven phase contrast enhancement to the limit, revealing low contrast features which would otherwise remain hidden under an excessive noise. Until today this possibility was hindered, in many objects of scientific interest, by the simultaneous presence of strong phase gradient regions and low contrast features. The strong gradients, when enhanced with the now possible long propagation distances, induce such strong phase effects that the linearisation assumptions of current state-of-the-art single-distance phase retrieval filters are broken, and the resulting image quality is jeopardized. Here, we introduce a new iterative phase-retrieval algorithm and compare it with the Paganin phase-retrieval algorithm, in both the monochromatic and polychromatic cases, obtaining superior image quality. In the polychromatic case the comparison was done with an extrapolated Paganin algorithm obtained by reintroducing, into our phase retrieval algorithm, the linearization approximations underlying the Paganin forward model. Our work provides an innovative algorithm which efficiently performs the phase retrieval task over the entire near-field range, producing images of exceptional quality for mixed attenuation objects.

Automated blood vessel segmentation is vital for biomedical imaging, as vessel changes indicate many pathologies. Still, precise segmentation is difficult due to the complexity of vascular structures, anatomical variations across patients, the scarcity of annotated public datasets, and the quality of images. We present a thorough literature review, highlighting the state of machine learning techniques across diverse organs. Our goal is to provide a foundation on the topic and identify a robust baseline model for application to vascular segmentation in a new imaging modality, Hierarchical Phase Contrast Tomography (HiP CT). Introduced in 2020 at the European Synchrotron Radiation Facility, HiP CT enables 3D imaging of complete organs at an unprecedented resolution of ca. 20mm per voxel, with the capability for localized zooms in selected regions down to 1mm per voxel without sectioning. We have created a training dataset with double annotator validated vascular data from three kidneys imaged with HiP CT in the context of the Human Organ Atlas Project. Finally, utilising the nnU Net model, we conduct experiments to assess the models performance on both familiar and unseen samples, employing vessel specific metrics. Our results show that while segmentations yielded reasonably high scores such as clDice values ranging from 0.82 to 0.88, certain errors persisted. Large vessels that collapsed due to the lack of hydrostatic pressure (HiP CT is an ex vivo technique) were segmented poorly. Moreover, decreased connectivity in finer vessels and higher segmentation errors at vessel boundaries were observed. Such errors obstruct the understanding of the structures by interrupting vascular tree connectivity. Through our review and outputs, we aim to set a benchmark for subsequent model evaluations using various modalities, especially with the HiP CT imaging database.

Artificial intelligence (AI) researchers have been developing and refining large language models (LLMs) that exhibit remarkable capabilities across a variety of domains and tasks, challenging our understanding of learning and cognition. The latest model developed by OpenAI, GPT-4, was trained using an unprecedented scale of compute and data. In this paper, we report on our investigation of an early version of GPT-4, when it was still in active development by OpenAI. We contend that (this early version of) GPT-4 is part of a new cohort of LLMs (along with ChatGPT and Google's PaLM for example) that exhibit more general intelligence than previous AI models. We discuss the rising capabilities and implications of these models. We demonstrate that, beyond its mastery of language, GPT-4 can solve novel and difficult tasks that span mathematics, coding, vision, medicine, law, psychology and more, without needing any special prompting. Moreover, in all of these tasks, GPT-4's performance is strikingly close to human-level performance, and often vastly surpasses prior models such as ChatGPT. Given the breadth and depth of GPT-4's capabilities, we believe that it could reasonably be viewed as an early (yet still incomplete) version of an artificial general intelligence (AGI) system. In our exploration of GPT-4, we put special emphasis on discovering its limitations, and we discuss the challenges ahead for advancing towards deeper and more comprehensive versions of AGI, including the possible need for pursuing a new paradigm that moves beyond next-word prediction. We conclude with reflections on societal influences of the recent technological leap and future research directions.