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In-lab, marker-based gait analyses may not represent real-world gait. Real-world gait analyses may be feasible using inertial measurement units (IMUs) in combination with open-source data processing pipelines (OpenSense). Before using OpenSense to study real-world gait, we must determine whether these methods estimate joint kinematics similarly to traditional marker-based motion capture (MoCap) and differentiate groups with clinically different gait mechanics. Healthy young and older adults and older adults with knee osteoarthritis completed this study. We captured MoCap and IMU data during overground walking at 2 speeds. MoCap and IMU kinematics were computed with OpenSim workflows. We tested whether sagittal kinematics differed between MoCap and IMU, whether tools detected between-group differences similarly, and whether kinematics differed between tools by speed. MoCap showed more anterior pelvic tilt (0%–100% stride) and joint flexion than IMU (hip: 0%–38% and 61%–100% stride; knee: 0%–38%, 58%–89%, and 95%–99% stride; and ankle: 6%–99% stride). There were no significant tool-by-group interactions. We found significant tool-by-speed interactions for all angles. While MoCap- and IMU-derived kinematics differed, the lack of tool-by-group interactions suggests consistent tracking across clinical cohorts. Results of the current study suggest that IMU-derived kinematics with OpenSense may enable reliable evaluation of gait in real-world settings.

To examine workload, thermal discomfort, and heat-related symptoms among healthcare workers (HCWs) in an Australian emergency department during the COVID-19 pandemic.A cross-sectional study design was employed among HCWs in an emergency department at a metropolitan hospital in Brisbane, Australia. Respondents provided demographic information including their self-reported age, sex, height, weight, role (e.g., doctor, nurse), and whether they wore PPE during their shift, rated as either Full PPE, Partial PPE, or usual uniform or scrubs. The workload of HCWs was assessed with the National Aeronautics and Space Administration's task load index (NASA-TLX). Thermal discomfort was evaluated using scales from the International Organisation for Standardisation. Responders rated their subjective heat illness using the Environmental Symptoms Questionnaire (ESQ-SHI).Fifty-nine HCWs completed the survey (27 male, 31 female). Overall workload from the NASA-TLX was 64.6 (IQR: 56.5-73.3) for doctors, 72.5 (IQR: 63.3-83.3) for nurses, and 66.7 (IQR: 58.3-74.17) for other staff, representing moderate to high ratings. Eighty-one percent reported thermal sensation to be slightly warm, warm, or hot, and 88% reported being uncomfortable, ranging from slightly to extremely. Ninety-seven percent reported at least one heat-strain symptom. More than 50% reported light-headedness or headache and approximately 30% reported feeling dizzy, faint, or weak.Emergency department HCWs experience thermal discomfort when wearing PPE. Combined with their workloads, HCWs experienced symptoms related to heat strain. Therefore, careful consideration should be given to managing heat strain among HCWs when wearing PPE in an Emergency Department. This article is protected by copyright. All rights reserved.

Background/Aims Systemic lupus erythematosus, systemic vasculitis, inflammatory myositis, scleroderma and Sjogren’s syndrome are rare autoimmune rheumatic diseases (RAIRDs). A survey of people with RAIRDs found 61% were struggling, 45% had reduced/stopped work and 45% reported an impact on family life. A survey of NHS rheumatology departments found 80% do not offer access to self-management support to people with RAIRDs. Aims: To understand the patients’ experiences of their RAIRD and views on interventions to support self-management, including content and structure. Methods Online focus groups via Zoom using a topic guide developed with a multi-disciplinary team including patient partners with lived experience. Focus groups were advertised via patient charities’ social media platforms (Vasculitis UK, Scleroderma and Raynaud’s UK, Lupus UK, Myositis UK and the British Sjogren’s Syndrome Association). Sessions were audio-recorded, transcribed, organised using NVIVO, and analysed thematically. Results Twenty-six patients, 21 (80.76 %) female, median age 62 (range 34-82), participated in six focus groups. Diagnoses included systemic lupus erythematosus (4), inflammatory myositis (7), ANCA-associated vasculitis (5), mixed connective tissue disease (2), scleroderma (1), undifferentiated vasculitis (2), and primary or secondary Sjogren’s (16). Five patients (19%) were newly diagnosed ( Two related main themes capture the data:“I’m constantly doing medical admin along with surviving and fighting a disease.” A lack of joined-up healthcare (“I’ve got some great people but they’re not working as a team”), difficulty accessing specialists (“Everyone just passes you like the sort of parcel that no one wants to open”) and disease complexity (“she said you’re too complicated”) makes managing RAIRDs hard, resource-intensive work (“I’ve had to push so hard for all of it and I think that only happens with very rare conditions”).“Because you have very rare conditions it’s uniquely isolating.” The psychological impact of having complex autoimmune conditions can be exacerbated when they are poorly understood by family and friends (“I’ve encountered mental health problems having to manage family expectations of me”) and health professionals (“they’ve never seen a patient like me in their life”). Patients described strategies that could be beneficial at an individual level (“acceptance, mindfulness, meditation and to not beat myself up about things”) and the importance of addressing mental health (“you’ve got to build your self-esteem, so you don’t feel rubbish all the time”). Conclusion Patients with RAIRDs identified shared experiences to inform the development of a cross-condition self-management intervention. These include negotiating healthcare systems and managing the psychological impact of RAIRDs. Further work is needed with under-represented groups to identify whether their support needs are distinct. Disclosure E. Dures: None. C. Almeida: None. A. Hunt: None. P.C. Lanyon: None. N. Walsh: None. J.C. Robson: None.

This interview considers Matthew Higgs’s role in programming work by self-taught artists and those with developmental disabilities within the context of White Columns, a non-profit artist-run space located in Chelsea, New York City. The conversation describes the active support of work before any critical or institutional consensus emerges around it and explores how painting by self-taught artists and those with developmental disabilities can provide a productive counterpoint to self-reflexive work or art more critical of the narrative of painting as a medium. The term ‘outsider’ is also scrutinized as a useful generalization for painting that operates outside of conventional forms of education and existing foundational narratives in culture. Also discussed is the impact of exemplary historical curators and dealers in the United States and Germany who serve to act as model ‘maverick iconoclasts’.

The editorial surveys the current terrain of contemporary self-taught and outsider art. Using Deleuze and Guattari’s Towards a Minor Literature to suggest a specific category of minor painting, the text discusses how museological discourse on outsider art that developed over the twentieth century has been transformed over the past decade by large museum exhibitions and smaller community organizations’ activities. These include key examples such as the National Gallery of Art, Washington’s exhibition Outliers and American Vanguard Art curated by Lynne Cooke, and White Columns’s exemplary programme that supports visionary and self-taught artists in New York City. The text outlines how these examples alongside curatorial activism and reappraisal have attempted to recalibrate art history and provides an analysis of the inclusion of outsider and self-taught art in biennales such as Venice, quinquennials such as Documenta and small publicly funded spaces with a desire for equality and inclusion.

Objectives Patient activation covers the skills, abilities and behaviour that impact how able and willing someone is to take an active role in self-managing their health. This study explored clinical and psychosocial factors associated with patient activation in rheumatology patients. Methods This was a cross-sectional study using postal survey methods. Participants with inflammatory rheumatic conditions were from six rheumatology centres in England. Patient activation was captured using the Patient Activation Measure (PAM). Twenty-nine explanatory factors were tested for potential association with patient activation in univariable and multivariable analyses. In preliminary multivariable analyses, factors found to have an association with patient activation at a P Results The sample comprised 251 participants (74% female) with a mean age of 59.31 years (s.d. 12.69), disease duration of 14.48 years (s.d. 12.52) and a PAM score of 58.3 (s.d. 11.46). Of the 29 candidate factors, 25 were entered into a preliminary multivariable analysis. In the final multivariable analysis, four factors (self-efficacy, the illness belief that treatment will control participants’ condition and two dimensions of health literacy) were significantly associated with patient activation. This final model accounted for 40.4% of the variance in PAM scores [F(4, 246) = 41.66, P Conclusions Patient activation is important in managing rheumatic conditions. Our data confirm that self-efficacy and health literacy are particular targets for patient activation interventions.

Designer gates Signaling in cells can occur through protein-protein interactions. Chen et al. describe the design of logic gates that can regulate protein association. The gates were built from small, designed proteins that all have a similar structure but where one module can be designed to interact specifically with another module. Using monomers and covalently connected monomers as inputs and encoding specificity through designed hydrogen-bond networks allowed the construction of two-input or three-input gates based on competitive binding. The modular control elements were used to regulate the association of elements of transcription machinery and split enzymes in vitro and in yeast cells. Science , this issue p. 78

A new approach to modelling asset portfolio capital investment and operational plans using a rationalisation process of multiple asset life cycle cost model’s is presented. It overcomes the traditional limitations of stocastic models which do not explicitly consider deliverability issues such as scrarce resources, access in combination with an organisations objectives and finamcial imapcts. The approach builds on earlier work including the Strategic Asset Lifecycle Value Optimisation (SALVO) research and development project and rational decision making. It uses individual life cycle cost models for each asset class and programme-level constraints and multi-criteria to create an optimal plan with transparent cost/benefit/risk justification. Alternative scenarios can then be developed from this idealised plan using significance cooling and hill climbing algorithms. These explore the real-world constraints and competing objectives that might prevent such a plan from being delivered. In this way, a realistic and deliverable plan is produced, with fully quantified business impact of any constraints or programme changes that are required. Using the idealised plan as a benchmark, the rationalised variants and scenarios may be compared and a budget and resource-committed programme then selected. The approach is found to be equally applicable for capital investment, operations and maintenance activities, including the combined operational expenditures (OpEx) and capital (CapEx) plans at enterprise portfolio level. Further, its application is applicable for any industry and regulated or non-regulated asset managing organisations.

Electromagnetic metering offers significant promise in the measurement of low-conductivity medium like in multiphase flow. Such measurements rely on the measurement of conductivity contrasts formed by two medium of substances, one substance being conductive and the other being non-conductive. In these conditions, it is assumed that the permittivity-induced displacement current is small compared to eddy current induced by conductivity, therefore the displacement current is usually ignored. The present study demonstrates, through solution of the electromagnetic forward problem and pilot tests, that the temporal, spatial and frequency related permittivity and conductivity changes are all captured by the induced electrical voltage measurement. Permittivity reflects in the amplitude and the conductivity reflects both in the amplitude and the phase angle of the voltage. The weight of each parameter to the voltage measurement is studied here. The findings of the study disclose that an electromagnetic metering system may offer advantages in continuously monitoring and measuring hydrocarbon contents and solid concentrations via both the amplitude and phase shift changes.

Introduction\ud An important aspect of self-management is patient activation (the skills, abilities and confidence someone uses to actively manage their health). The dominant method of capturing patient activation is the Patient Activation Measure (PAM) which has been integrated into many aspects of clinical practice in musculoskeletal care. However, limited research has investigated how rheumatology patients understand and perform patient activation, and how closely their perceptions align with the PAM.\ud \ud Methods\ud Seventeen patients from two rheumatology departments in South West England participated in semi-structured interviews at two timepoints. They discussed how they actively managed their health and their views on the PAM. Data on activation were analysed using framework analysis and data on the PAM were analysed using content analysis.\ud \ud Results\ud Participants self-managed with determination, finding ways to make small, sustainable behaviour changes and effectively navigate the healthcare system. They reported the value of knowing what self-management techniques suited them individually and reported benefitting from positive perceptions of their own health and good social support. Participants noted that the PAM did not always capture the fluctuating nature of their inflammatory arthritis and the collaborative nature of healthcare.\ud \ud Conclusions\ud Patients' perceptions and experiences of patient activation covered a wide range of skills, behaviours and beliefs. However, these are not always captured by the PAM. Therefore, its use as a clinical tool is best accompanied by dialogue with patients to understand their self-management.

A key principle of working in collaboration with patient research partners (patients contributing to research projects as team members, rather than as participants) is that they should be equal partners with researchers and health professionals. This presents a challenge in doctoral research, where students are expected to own their research decisions. Consequently, efforts are required to ensure that patient partners’ involvements are not tokenistic. This case study brings together the reflections of a recently completed doctoral student and a patient partner, who was part of the doctoral supervisory team. It discusses the role that the patient partner took during the doctorate and the activities in which he was involved. Both the researcher and the patient partner reflect on their expectations and experiences of collaboration. These reflections include factors that facilitated good working practices, the process of building rapport, and the benefits each got out of their collaboration. The interactions exploring ‘the dance of academia’ (the processes that were formally part of the PhD process or the aspects of academic work that were not directly related to completing the research) required recognition. Open, ongoing communication and practical considerations to support the patient partner were key to establishing a strong working relationship, and to determining what a meaningful contribution looked like at each stage of the process. Working with a patient partner as a doctoral student adds value to the doctoral process, and it is a vital opportunity to develop good practice as a researcher.

Common in-lab, marker-based gait analyses may not represent daily, real-world gait. Real-world gait analyses may be feasible using inertial measurement units (IMUs), especially with recent advancements in open-source methods (e.g., OpenSense). Before using OpenSense to study real-world gait, we must determine whether these methods: (1) estimate joint kinematics similarly to traditional marker-based motion capture (MoCap) and (2) differentiate groups with clinically different gait mechanics. Healthy young and older adults and older adults with knee osteoarthritis completed this study. We captured MoCap and IMU data during overground walking at participants’ self-selected and faster speeds. MoCap and IMU kinematics were computed with appropriate OpenSim workflows. We tested whether sagittal kinematics differed between MoCap- and IMU-derived data, whether tools detected between-group differences similarly, and whether kinematics differed between tools by speed. MoCap data showed more flexion than IMU data (hip: 0-47 and 65-100% stride, knee: 0-38 and 58-91% stride, ankle: 18-100% stride). Group kinematics differed at the hip (young extension > knee osteoarthritis at 30-47% stride) and ankle (young plantar flexion > older healthy at 62-65% stride). Group-by-tool interactions occurred at the hip (61-63% stride). Significant tool-by-speed interactions were found, with hip and knee flexion increasing more for MoCap than IMU data with speed (hip: 12-15% stride, knee: 60-63% stride). While MoCap- and IMU-derived kinematics differed, our results suggested that the tools similarly detected clinically meaningful differences in gait. Results of the current study suggest that IMU-derived kinematics with OpenSense may enable the valid and reliable evaluation of gait in real-world, unobserved settings.

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this gap by developing an automated workflow combining cell-free DNA template generation, protein synthesis, and high-throughput binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to 119 published SARS-CoV-2 neutralizing antibodies and demonstrate rapid identification of the most potent antibody candidates.

Purpose: Patients with small cell lung cancer (SCLC) who have brain metastases require whole-brain radiation therapy (WBRT). When there is no emergent indication for WBRT, patients may receive systemic therapy first and WBRT afterward. In scenarios when systemic therapy is initiated first, it has not been previously investigated whether delaying WBRT is harmful. Methods and Materials: The National Cancer Database was queried (2004-2016) for patients with SCLC with brain metastases who received 30 Gy in 10 fractions of WBRT. Patients were divided into groups based on whether they received early WBRT (3-14 days after initiation of chemotherapy) or late WBRT (15-90 days after initiation of chemotherapy). Demographic and clinicopathologic categorical variables were compared between those who had early WBRT (3-14 days) and those who had late WBRT (15-90 days). Factors predictive for late WBRT were determined. Overall survival (OS), which was defined as days from diagnosis to death, was evaluated and variables prognostic for OS were determined. Results: A total of 1082 patients met selection criteria; 587 (54%) had early WBRT and 495 (46%) received late WBRT. Groups were similarly distributed aside from days from initiating chemotherapy to initiating WBRT (P < .001). The early WBRT group had a median of 7 days (interquartile range [IQR], 5-10 days) from initiating chemotherapy to initiating WBRT and the late WBRT group had a median of 34 days (IQR, 21-57 days). On binary logistic regression analysis, a longer time interval between diagnosis and the start of systemic therapy was predictive for later WBRT. Median OS was 8.7 months for early WBRT and 7.5 months for late WBRT (hazard ratio [HR], 1.165; P = .008). Early WBRT (P = .02), female sex (P = .045), and private insurance (P = .04) were favorable prognostic factors for OS on multivariable analysis, whereas older age (P = .006) was an unfavorable prognostic factor. Conclusions: Patients with SCLC and brain metastases who received early WBRT were found to have a modest improvement in OS compared with patients who received late WBRT. These findings suggest that early WBRT should be offered to patients who have brain metastases, even in the absence of an indication for emergent WBRT.

Dynamic control over protein function is a central challenge in synthetic biology. To address this challenge, we describe the development of an integrated computational and experimental workflow to incorporate a metal-responsive chemical switch into proteins. Pairs of bipyridinylalanine (BpyAla) residues are genetically encoded into two structurally distinct enzymes, a serine protease and firefly luciferase, so that metal coordination biases the conformations of these enzymes, leading to reversible control of activity. Computational analysis and molecular dynamics simulations are used to rationally guide BpyAla placement, significantly reducing experimental workload, and cell-free protein synthesis coupled with high-throughput experimentation enable rapid prototyping of variants. Ultimately, this strategy yields enzymes with a robust 20-fold dynamic range in response to divalent metal salts over 24 on/off switches, demonstrating the potential of this approach. We envision that this strategy of genetically encoding chemical switches into enzymes will complement other protein engineering and synthetic biology efforts, enabling new opportunities for applications where precise regulation of protein function is critical.

Escape variants of SARS-CoV-2 are threatening to prolong the COVID-19 pandemic. To address this challenge, we developed multivalent protein-based minibinders as potential prophylactic and therapeutic agents. Homotrimers of single minibinders and fusions of three distinct minibinders were designed to geometrically match the SARS-CoV-2 spike (S) trimer architecture and were optimized by cell-free expression and found to exhibit virtually no measurable dissociation upon binding. Cryo-electron microscopy (cryoEM) showed that these trivalent minibinders engage all three receptor binding domains on a single S trimer. The top candidates neutralize SARS-CoV-2 variants of concern with IC50 values in the low pM range, resist viral escape, and provide protection in highly vulnerable human ACE2-expressing transgenic mice, both prophylactically and therapeutically. Our integrated workflow promises to accelerate the design of mutationally resilient therapeutics for pandemic preparedness., One-Sentence Summary: We designed, developed, and characterized potent, trivalent miniprotein binders that provide prophylactic and therapeutic protection against emerging SARS-CoV-2 variants of concern.

The agglutinated foraminiferal species Sculptobaculitesgoodlandensis has been studied to determine the composition of the cement and grains that make up the test wall. Elemental mapping of the internal structure reveals a layered wall with quartz grains in calcitic cement on the edges of the wall and an inner, calcitic layer of mixed detrital calcareous grains and fine-grained calcite, presumed to be secreted calcitic cement.

Linear Discriminant Analysis (LDA) yields the optimal Bayes classifier for binary classification for normally distributed classes with equal covariance. To improve the performance of LDA, heteroscedastic LDA (HLDA) that removes the equal covariance assumption has been developed. In this paper, we show using first and second-order optimality conditions that the existing approaches either have no principled computational procedure for optimal parameter selection, or underperform in terms of the accuracy of classification and the area under the receiver operating characteristics curve (AUC) under class imbalance. Using the same optimality conditions, we then derive a dynamic Bayes optimal linear classifier for heteroscedastic LDA that is optimised via an efficient iterative procedure, which is robust against class imbalance. Experimental work is conducted on two artificial and eight real-world datasets. Our results show that the proposed algorithm compares favourably with the existing heteroscedastic LDA procedures as well as the linear support vector machine (SVM) in terms of the error rate, but is superior to all the algorithms in terms of the AUC under class imbalance. The fast training time of the proposed algorithm also encourages its use for large-data applications that show high incidence of class imbalance, such as in human activity recognition.

Accurate metering of slug flows is important in many industries that handle multiphase products. For the oil and gas industry the harsh environmental conditions mean that non-invasive and non-intrusive instruments are preferred. Cross-correlation meters, particularly those based on electrical tomography, offer a potential solution to this problem but sufficient accuracy has proved difficult to achieve, with the primary issue being that the measurement is dominated by the motion of interfaces rather than the bulk fluid. In the work reported here, results are presented for flows of oil and nitrogen gas in a horizontal pipe of diameter 10.2 cm. Superficial velocities of liquid and gas range from 1 m/s to 3 m/s and 0.4–3 m/s respectively. By analysing the structures of liquid slugs via tomography, it is found that three significantly different slug front structures occur. The high-speed and spatial resolution of Electrical Capacitance Tomography (ECT) enables independent measurement of individual slug fronts and tail as well as average slug velocity. Based on detailed measurements of slug structures and velocity profiles, we go on to show that using differential-based cross-correlation and the average velocity of slug front and tail, an overall accuracy of better than + / − 5 % is achieved for estimation of the mixture superficial velocity. This is an equivalent level of accuracy to that obtained using intrusive methods such as optical fibre probes, which are less suitable for oil and gas applications.