Silicon Ether Ionizable Lipids Enable Potent mRNA Lipid Nanoparticles with Rapid Tissue Clearance.

The advent of mRNA for nucleic acid (NA) therapeutics has unlocked many diverse areas of research and clinical investigation. However, the shorter intracellular half-life of mRNA compared with other NAs may necessitate more frequent dosing regimens. Because lipid nanoparticles (LNPs) are the principal delivery system used for mRNA, this could lead to tolerability challenges associated with an accumulated lipid burden. This can be addressed by introducing enzymatically cleaved carboxylic esters into the hydrophobic domains of lipid components, notably, the ionizable lipid. However, enzymatic activity can vary significantly with age, disease state, and species, potentially limiting the application in humans. Here we report an alternative approach to ionizable lipid degradability that relies on nonenzymatic hydrolysis, leading to a controlled and highly efficient lipid clearance profile. We identify highly potent examples and demonstrate their exceptional tolerability in multiple preclinical species, including multidosing in nonhuman primates (NHP).

A conceptual framework on the role of magnetic cues in songbird migration ecology.

Migrating animals perform astonishing seasonal movements by orienting and navigating over thousands of kilometres with great precision. Many migratory species use cues from the sun, stars, landmarks, olfaction and the Earth's magnetic field for this task. Among vertebrates, songbirds are the most studied taxon in magnetic-cue-related research. Despite multiple studies, we still lack a clear understanding of when, where and how magnetic cues affect the decision-making process of birds and hence, their realised migratory behaviour in the wild. This understanding is especially important to interpret the results of laboratory experiments in an ecologically appropriate way. In this review, we summarise the current findings about the role of magnetic cues for migratory decisions in songbirds. First, we review the methodological principles for orientation and navigation research, specifically by comparing experiments on caged birds with experiments on free-flying birds. While cage experiments can show the sensory abilities of birds, studies with free-flying birds can characterise the ecological roles of magnetic cues. Second, we review the migratory stages, from stopover to endurance flight, in which songbirds use magnetic cues for their migratory decisions and incorporate this into a novel conceptual framework. While we lack studies examining whether and when magnetic cues affect orientation or navigation decisions during flight, the role of magnetic cues during stopover is relatively well studied, but mostly in the laboratory. Notably, many such studies have produced contradictory results so that understanding the biological importance of magnetic cues for decisions in free-flying songbirds is not straightforward. One potential explanation is that reproducibility of magnetic-cue experiments is low, probably because variability in the behavioural responses of birds among experiments is high. We are convinced that parts of this variability can be explained by species-specific and context-dependent reactions of birds to the study conditions and by the bird's high flexibility in whether they include magnetic cues in a decision or not. Ultimately, this review should help researchers in the challenging field of magnetoreception to design experiments meticulously and interpret results of such studies carefully by considering the migration ecology of their focal species.

Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial.

BACKGROUND: Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED-based smoking cessation intervention can help people to quit smoking. METHODS: In this multicentre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at 6 months. RESULTS: An intention-to-treat analysis included 972 of 1443 people screened for inclusion (484 in the intervention group, 488 in the control group). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The 6-month biochemically-verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk 1.76; 95% CI 1.03 to 3.01; p=0.038). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk 1.80; 95% CI 1.36 to 2.38; p<0.001). No serious adverse events related to taking part in the trial were reported. CONCLUSIONS: An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events. TRIAL REGISTRATION NUMBER: NCT04854616.

The effect of observing trained conspecifics on the performance and motivation of goldfish, Carassius auratus, in a spatial task.

Spatial and social cognition are two aspects of fish behaviour that have been subject to an increasing amount of research in recent years, but few have investigated potential behaviour overlaps. Testing the ability for an individual to socially learn a spatial task would bridge this gap in understanding. We provided naïve goldfish, Carassius auratus, the opportunity to observe a trained conspecific navigate a T-shaped maze, and then recorded how many trials it took for them to learn the maze, time taken per trial, motivation, and acceptance of the food reward. We also recorded how many trials it took a control group to learn the maze without the opportunity to observe a demonstrator. The observer group took significantly longer to learn the maze than the control group. Although the observer group were significantly less motivated (trials without a choice made), they were significantly more likely to accept the food reward. The social learning of reward acceptance was taking place, but the process of the demonstration disrupted the training of the spatial task, with possible explanations as the passenger effect and trade-off mechanism being discussed. Future studies are needed to determine whether goldfish can acquire spatial information socially; however, this study contributes to the feasibility of studying social learning of environmentally information in goldfish.

Taxonomy development for term standardization in activity resulting from medication review processes: a Delphi study.

BACKGROUND: Medication review (MR) is the systematic assessment of a patient's medications for safety and effectiveness by a healthcare professional. The language used to describe MR activity, such as stopped medicine and increased dose, should be consistent across studies to assist researchers compare how different services operate and identify their mechanism of impact. AIM: To develop an international taxonomy of standardized terms and activity definitions related to medication reviews. METHOD: This was a three-stage Delphi-based consensus study with international medication review experts. A systematic review provided MR activity terms for the survey. Experts rated their consensus on each activity term and its definition on a Likert scale and provided written feedback. The consensus was 75% panel agreement. At each stage, consensus elements were retained, and feedback was used to revise definitions. RESULTS: Seven experts were recruited for the study (response rate 15.2%) from four countries: the United Kingdom (n = 4), New Zealand (n = 1), Australia (n = 1), and Malaysia (n = 1). The following terms achieved consensus: the term Medication as a descriptor for MR terms; discontinue medication, start medication, dose increase, dose decrease, dosage form change, and medication safety and efficacy monitor to describe MR activity; Educate to describe the delivery of healthcare professionals and patients/carers education. CONCLUSION: Standardized medication review activity terms and definitions have been selected for universal adoption in all future MR research to facilitate a meaningful comparison of process evaluations within different settings.

Migratory bats are sensitive to magnetic inclination changes during the compass calibration period.

The Earth's magnetic field is used as a navigational cue by many animals. For mammals, however, there are few data to show that navigation ability relies on sensing the natural magnetic field. In night-time migrating bats, experiments demonstrating a role for the solar azimuth at sunset in the calibration of the orientation system suggest that the magnetic field is a candidate for their compass. Here, we investigated how an altered magnetic field at sunset changes the nocturnal orientation of the bat Pipistrellus pygmaeus. We exposed bats to either the natural magnetic field, a horizontally shifted field (120°), or the same shifted field combined with a reversal of the natural value of inclination (70° to -70°). We later released the bats and found that the take-off orientation differed among all treatments. Bats that were exposed to the 120° shift were unimodally oriented northwards in contrast to controls which exhibited a bimodal north-south distribution. Surprisingly, the orientation of bats exposed to both a 120° shift and reverse inclination was indistinguishable from a uniform distribution. These results suggest that these migratory bats calibrate the magnetic field at sunset, and for the first time, they show that bats are sensitive to the angle of magnetic inclination.

BabyBreathe trial: protocol for a randomised controlled trial of a complex intervention to prevent postpartum return to smoking.

INTRODUCTION: Many people quit smoking during pregnancy, but postpartum smoking relapse is common. Maintaining smoking abstinence achieved during pregnancy is key to improving maternal and child health. There are no evidence-based interventions for preventing postpartum smoking relapse. This trial aims to determine whether an intervention to prevent postpartum relapse is effective and cost-effective. METHODS AND ANALYSIS: A randomised controlled trial of a complex intervention to prevent postpartum smoking relapse (BabyBreathe), with internal pilot, economic and process evaluations. Participants are adults who are pregnant and who report having quit smoking in the 12 months before, or during pregnancy. Participants are eligible if they read and understand English, and provide informed consent. Following consent and biochemical validation of smoking abstinence, participants are randomised to intervention or usual care/control (no specific relapse prevention support). The BabyBreathe intervention consists of manualised advice from a trained member of the health visiting service, health information leaflets for participants and partners, access to the BabyBreathe website and app. At the time of birth, participants are posted the BabyBreathe box and support is provided by text message for up to 12 months postpartum. Target sample size is 880, recruiting across midwifery services at four hubs in England and Scotland and through remote advertising in England, Scotland, Wales and Northern Ireland. Outcomes are collected at 6 and 12 months. The primary outcome is self-reported sustained smoking abstinence at 12 months, carbon monoxide verified. Secondary outcomes include self-reported abstinence, time to relapse, partner smoking status and quality of life. ETHICS AND DISSEMINATION: The trial was approved by the North West Preston Research Ethics committee (21/NW/0017). Dissemination will include publication in peer-reviewed journals, presentation at academic and public conferences including patient and public involvement and to policymakers and practitioners. TRIAL REGISTRATION NUMBER: ISRCTN70307341.

Why might medical student empathy change throughout medical school? a systematic review and thematic synthesis of qualitative studies.

BACKGROUND: Several studies suggest that medical student empathy declines throughout medical school. However, no studies have synthesised the evidence regarding why empathy declines. OBJECTIVE: To conduct a systematic review and thematic synthesis of qualitative studies investigating why student empathy may change throughout medical school. METHODS: We included any qualitative study that investigated why empathy might change during medical school. We searched the Medline, Scopus, CINAHL, ERIC, and APA PsycInfo databases for relevant studies. All databases were searched from their inception to 18 July 2022. We also searched the reference lists of the included studies and contacted experts to identify additional studies. We used the Joanna Briggs Institute tool to evaluate the risk of bias in the included studies. Overall confidence in our results was assessed using the Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach. We used thematic methods to synthesise our findings. RESULTS: Our searches yielded 2523 records, and 16 studies involving a total of 771 students were eligible for analysis. Most studies (n = 11) were from Europe or North America. The descriptive themes and sub-themes were identified for each study. Increased complexity in patients and their diseases, together with the 'hidden curriculum' (including a stressful workload, prioritisation of biomedical knowledge, and (sometimes) poor role models), led to student adaptations, such as cynicism and desensitisation. Students' prior lives and professional experiences appeared to exacerbate the decline in empathy. However, there were bias concerns for most of the included studies. DISCUSSION: Many of the included studies included were small, and some did not include demographic participant data. Given the likely benefits of providing empathic care for patients and practitioners, medical education interventions should focus on developing an 'empathic hidden curriculum' that mitigates the decline in medical student empathy. TRIAL REGISTRATION: A protocol for this systematic review was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on 28 July 2022 (registration number CRD42022347856).

Evaluation of effectiveness and safety of pharmacist independent prescribers in care homes: cluster randomised controlled trial.

OBJECTIVE: To estimate the effectiveness, cost effectiveness (to be reported elsewhere), and safety of pharmacy independent prescribers in care homes. DESIGN: Cluster randomised controlled trial, with clusters based on triads of a pharmacist independent prescriber, a general practice, and one to three associated care homes. SETTING: Care homes across England, Scotland, and Northern Ireland, their associated general practices, and pharmacy independent prescribers, formed into triads. PARTICIPANTS: 49 triads and 882 residents were randomised. Participants were care home residents, aged ≥65 years, taking at least one prescribed drug, recruited to 20 residents/triad. INTERVENTION: Each pharmacy independent prescriber provided pharmaceutical care to approximately 20 residents across one to three care homes, with weekly visits over six months. Pharmacy independent prescribers developed a pharmaceutical care plan for each resident, did medicines reviews/reconciliation, trained staff, and supported with medicines related procedures, deprescribing, and authorisation of prescriptions. Participants in the control group received usual care. MAIN OUTCOMES MEASURES: The primary outcome was fall rate/person at six months analysed by intention to treat, adjusted for prognostic variables. Secondary outcomes included quality of life (EQ-5D by proxy), Barthel score, Drug Burden Index, hospital admissions, and mortality. Assuming a 21% reduction in falls, 880 residents were needed, allowing for 20% attrition. RESULTS: The average age of participants at study entry was 85 years; 70% were female. 697 falls (1.55 per resident) were recorded in the intervention group and 538 falls (1.26 per resident) in the control group at six months. The fall rate risk ratio for the intervention group compared with the control group was not significant (0.91, 95% confidence interval 0.66 to 1.26) after adjustment for all model covariates. Secondary outcomes were not significantly different between groups, with exception of the Drug Burden Index, which significantly favoured the intervention. A third (185/566; 32.7%) of pharmacy independent prescriber interventions involved medicines associated with falls. No adverse events or safety concerns were identified. CONCLUSIONS: Change in the primary outcome of falls was not significant. Limiting follow-up to six months combined with a small proportion of interventions predicted to affect falls may explain this. A significant reduction in the Drug Burden Index was realised and would be predicted to yield future clinical benefits for patients. This large trial of an intensive weekly pharmacist intervention with care home residents was also found to be safe and well received. TRIAL REGISTRATION: ISRCTN 17847169.

Sense of doubt: inaccurate and alternate locations of virtual magnetic displacements may give a distorted view of animal magnetoreception ability.

Virtual magnetic displacements are used to examine the magnetoreceptive ability of animals by changing the local magnetic field to emulate one that exists elsewhere. This technique can be used to test whether animals use a magnetic map. The viability of a magnetic map is dependant upon which magnetic parameters an animal's coordinate system is composed of, and how sensitive they are to those parameters. Previous research has not considered the degree to which sensitivity can change an animal's impression of where a virtual magnetic displacement is located. We re-assessed all published studies that use virtual magnetic displacements assuming the highest likely level of sensitivity to magnetic parameters in animals. The vast majority are susceptible to the existence of alternate possible virtual locations. In some cases, this can cause results to become ambiguous. We present a tool for visualising all possible virtual magnetic displacement alternative locations (ViMDAL) and propose changes to how further research on animal magnetoreception is conducted and reported.

Cessation of smoking trial in the emergency department (CoSTED): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Attendees of emergency departments (EDs) have a higher than expected prevalence of smoking. ED attendance may be a good opportunity to prompt positive behaviour change, even for smokers not currently motivated to quit. This study aims to determine whether an opportunist smoking cessation intervention delivered in the ED can help daily smokers attending the ED quit smoking and is cost-effective. METHODS AND ANALYSIS: A two-arm pragmatic, multicentred, parallel-group, individually randomised, controlled superiority trial with an internal pilot, economic evaluation and mixed methods process evaluation. The trial will compare ED-based brief smoking cessation advice, including provision of an e-cigarette and referral to local stop smoking services (intervention) with the provision of contact details for local stop smoking services (control). Target sample size is 972, recruiting across 6 National Health Service EDs in England and Scotland. Outcomes will be collected at 1, 3 and 6 months. The primary outcome at 6 months is carbon monoxide verified continuous smoking abstinence. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Oxford B Research Committee (21/SC/0288). Dissemination will include the publication of outcomes, and the process and economic evaluations in peer-reviewed journals. The findings will also be appropriately disseminated to relevant practice, policy and patient representative groups. TRIAL REGISTRATION NUMBER: NCT04854616; protocol V.4.2.

Pharmacist-independent prescriber deprescribing in UK care homes: Contextual factors associated with increased activity.

AIMS: The Care Home Independent Pharmacist Prescriber Study (CHIPPS) process evaluation hypothesized that contextual factors influenced the likelihood of deprescribing by pharmacist-independent prescribers. The aim of this paper is to test this hypothesis. METHODS: From CHIPPS study data, medications deprescribed totalled 284 for 370 residents in UK care homes. Regression analysis was used to describe the relationship between the number of medicines stopped and contextual factors (number of residents cared for, pharmacist employment within associated medical practice, previous care home experience, hours active within trial, years' experience as a pharmacist and as a prescriber). RESULTS: Number of residents and pharmacist-independent prescriber employment within a medical practice were positive predictors of deprescribing. CONCLUSION: Previous experiences were not related to deprescribing likelihood. Increasing the number of residents increases the opportunity for deprescribing and therefore this relationship is intuitive. The location within a medical practice is an interesting finding that requires further exploration to understand its exact nature.

Combination treatment of mannose and GalNAc conjugated small interfering RNA protects against lethal Marburg virus infection.

Marburg virus (MARV) infection results in severe viral hemorrhagic fever with mortalities up to 90%, and there is a pressing need for effective therapies. Here, we established a small interfering RNA (siRNA) conjugate platform that enabled successful subcutaneous delivery of siRNAs targeting the MARV nucleoprotein. We identified a hexavalent mannose ligand with high affinity to macrophages and dendritic cells, which are key cellular targets of MARV infection. This ligand enabled successful siRNA conjugate delivery to macrophages both in vitro and in vivo. The delivered hexa-mannose-siRNA conjugates rendered substantial target gene silencing in macrophages when supported by a mannose functionalized endosome release polymer. This hexa-mannose-siRNA conjugate was further evaluated alongside our hepatocyte-targeting GalNAc-siRNA conjugate, to expand targeting of infected liver cells. In MARV-Angola-infected guinea pigs, these platforms offered limited survival benefit when used as individual agents. However, in combination, they achieved up to 100% protection when dosed 24 h post infection. This novel approach, using two different ligands to simultaneously deliver siRNA to multiple cell types relevant to infection, provides a convenient subcutaneous route of administration for treating infection by these dangerous pathogens. The mannose conjugate platform has potential application to other diseases involving macrophages and dendritic cells.

Cluster randomised control trial protocol for estimating the effectiveness and cost-effectiveness of a complex intervention to increase care home staff influenza vaccination rates compared to usual practice (FLUCARE).

The care home staff influenza vaccination rate in England is significantly lower than the 75% World Health Organisation recommendation. This represents a substantial potential for resident harm. Barriers to staff vaccination stem from individual and organisational levels. Existing interventions address some but not all barriers and are not underpinned by behavioural science theory. This study aims to estimate the effectiveness and cost-effectiveness of a theory-informed intervention to improve care home staff vaccination rates compared to routine practice.Set in care homes with both nursing and residential focus, and a range of ownership status, only homes providing long stay care to older people with a staff vaccination rate below 40% are eligible to participate. Participation expressions of interest will be sought using a variety of approaches prior to seeking consent.The primary outcome measure is the proportion of staff vaccinated at 6 months, with secondary outcome measures being proportion vaccinated at 3 months, numbers of staff sick days, general practitioner and nurse visits to care home, care home resident hospitalisations and mortality.Based on the assumptions that the mean cluster (care home) size is 54 staff, a coefficient of variation of 0.48, control vaccination rate is 55%, intervention 75%, intra-cluster correlation coefficient of 0.2 and with 90% power, and 20% attrition, we require 39 care homes per arm.Blocked randomisation will be at the level of care home, stratified by the proportion of non-white care home staff, and implemented by Norwich Clinical Trials Unit.The intervention comprises co-designed information videos and posters, provision of in-house staff vaccination clinics, and incentive scheme and monthly data collection on trial outcomes. Beyond usual practice, the control arm will additionally contribute monthly data.Data will be collected at the start, monthly and at 6 months, and analysis will be blind to allocation. Statistical analysis will use the intention-to-treat principle with the difference in vaccination rates between groups compared using a random effect logistic regression model at the staff-level.This will be the first study to use a theory-informed intervention designed to comprehensively address identified barriers to care home staff influenza vaccination.Trial registration: ISRCTN ISRCTN22729870 . Registered on 24 August 22. Secondary identifiers: R209939, IRAS 316820, CPMS 53812.

Why might medical student empathy change throughout medical school? Protocol for a systematic review and thematic synthesis of qualitative studies.

INTRODUCTION: Several studies suggest that medical student empathy declines throughout medical school. However, no studies have systematically investigated why. The objective of our proposed review is to conduct a systematic review and thematic synthesis of qualitative studies investigating the reasons empathy may change throughout medical school. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We have searched MEDLINE, Scopus, CINAHL, ERIC and APA PsycINFO for relevant studies. We will also search reference lists of included studies and contact experts to identify additional studies. We will include any qualitative study investigating the reasons why empathy changes throughout medical school. We will use the Joanna Briggs Institute tool to evaluate the risk of bias in the included studies. We will use thematic analysis to synthesise our results. For all included studies, we will summarise the main characteristics including the number of participants, medical school year, country and gender. In our discussion, we will summarise the limitations of the evidence (including the risk of bias and inconsistency), and provide a general interpretation of the results and important implications. ETHICS AND DISSEMINATION: This study will not require ethical approval since no original data will be collected. The results of this review will be published through peer-reviewed publications and conference presentations. Additionally, this review will inform changes to the enhanced empathy curriculum at the Leicester Medical School.

Enhancing deprescribing: A qualitative understanding of the complexities of pharmacist-led deprescribing in care homes.

The English National Overprescribing Review identified that older people often take eight or more medicines a day. The report recommended pharmacists in primary care should take responsibility for addressing polypharmacy. Overprescribing is a safety concern in care homes as approximately half of older care home residents are prescribed at least one medicine that is unnecessary or now harmful. This predisposes them to adverse outcomes including hospitalisation and mortality. Deprescribing is the planned activity of stopping or reducing a medicine that may no longer be appropriate. Deprescribing, when performed by a pharmacist, is a multidisciplinary activity requiring close communication with general practitioners (GPs) and care home staff. A recently completed trial that integrated pharmacists with prescribing rights into older peoples' care homes found significant variation in proactive deprescribing activity. The aim of the current study was to specifically explore beliefs and practices of deprescribing in care homes. A qualitative approach was adopted to examine individual, social and contextual factors that acted as enablers and barriers to pharmacist deprescribing in care homes. Semi-structured interviews were conducted with participants of the previous study (16 pharmacists, 6 GPs and 7 care home staff from Northern Ireland, Scotland and England). Using thematic analysis, we identified two themes: (a) Structures and systems affecting deprescribing, that is the context in which deprescribing happened, including team involvement and routine practices in GP surgeries and care homes; (b) Balancing risks when deprescribing, that is the perception of individual risk and social barriers were mitigated by understanding the medical background of residents. This supported the clinical understanding that risks from overprescribing were greater than risks from deprescribing. While deprescribing can involve all health professionals in the primary care team, these results suggest the pharmacist is well placed to lead the process; by having both clinical competence and professional willingness to drive this activity forward.

Development of a Smoke-Free Home Intervention for Families of Babies Admitted to Neonatal Intensive Care.

Neonatal intensive care units (NICUs) have a disproportionately higher number of parents who smoke tobacco compared to the general population. A baby's NICU admission offers a unique time to prompt behaviour change, and to emphasise the dangerous health risks of environmental tobacco smoke exposure to vulnerable infants. We sought to explore the views of mothers, fathers, wider family members, and healthcare professionals to develop an intervention to promote smoke-free homes, delivered on NICU. This article reports findings of a qualitative interview and focus group study with parents whose infants were in NICU (n = 42) and NICU healthcare professionals (n = 23). Thematic analysis was conducted to deductively explore aspects of intervention development including initiation, timing, components and delivery. Analysis of inductively occurring themes was also undertaken. Findings demonstrated that both parents and healthcare professionals supported the need for intervention. They felt it should be positioned around the promotion of smoke-free homes, but to achieve that end goal might incorporate direct cessation support during the NICU stay, support to stay smoke free (relapse prevention), and support and guidance for discussing smoking with family and household visitors. Qualitative analysis mapped well to an intervention based around the '3As' approach (ask, advise, act). This informed a logic model and intervention pathway.

Plain Radiographic Instruments for Structural Damage in Peripheral Joints in Psoriatic Arthritis: A Report From the GRAPPA-OMERACT Working Group.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is focused on the development of a core set of instruments used to assess the domains described in the 2016 PsA Core Domain Set. At the 2021 annual meeting, the group presented an update on the domain of structural damage. In this report, we discuss the steps taken to assess the domain match and feasibility of plain radiographic instruments in the assessment of structural damage in PsA.