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The shoulder joint is a complex array of muscles, tendons, and capsuloligamentous structures that has the greatest freedom of motion of any joint in the body. Acute (

Appropriate imaging modalities for screening, staging, and surveillance of patients with suspected and documented metastatic disease to bone include 99mTc bone scanning, MRI, CT, radiography, and 2-[18F]fluoro-2-deoxyglucose-PET. Clinical scenarios reviewed include asymptomatic stage 1 breast carcinoma, symptomatic stage 2 breast carcinoma, abnormal bone scan results with breast carcinoma, pathologic fracture with known metastatic breast carcinoma, asymptomatic well-differentiated and poorly differentiated prostate carcinoma, vertebral fracture with history of malignancy, non-small-cell lung carcinoma staging, symptomatic multiple myeloma, osteosarcoma staging and surveillance, and suspected bone metastasis in a pregnant patient. No single imaging modality is consistently best for the assessment of metastatic bone disease across all tumor types and clinical situations. In some cases, no imaging is indicated. The recommendations contained herein are the result of evidence-based consensus by the ACR Appropriateness Criteria® Expert Panel on Musculoskeletal Radiology. © 2010 American College of Radiology.

Imaging of the diabetic foot is among the most challenging areas of radiology. The authors present a consensus of the suggested tests in several clinical scenarios, such as early neuropathy, soft-tissue swelling, skin ulcer, and suspected osteomyelitis. In most of these situations, magnetic resonance imaging (MRI) with or without contrast is the examination of choice. Most other imaging tests have complementary roles. For soft-tissue swelling or an ulcer, radiography and MRI with or without contrast are suggested. Bone scintigraphy with white blood cell scanning is used when MRI is contraindicated. In patients with diabetes without ulcers, radiography and MRI with or without contrast are suggested; bone scanning may be used when MRI is contraindicated. [ABSTRACT FROM AUTHOR]

When interpreting musculoskeletal radiographs, a radiologist must be able to identify a lytic lesion and provide a definitive diagnosis or a reasonable differential diagnosis for the lesion. This article addresses these issues and details a rational and systematic approach to such lesions. [ABSTRACT FROM AUTHOR]

PURPOSE: To identify the health concerns for which adolescent residents in New South Wales, Australia, do not receive health care, and the associated factors, including their sociodemographic distribution. METHODS: Purposive sampling was used to recruit school students who were stratified by gender and age (12-14, 14-16 and 16-17 years), from schools stratified by socioeconomic status and urban/rural location. Out-of-school young people were recruited through youth health services. Qualitative methods were used to collect and analyze data. RESULTS: Eighty-one focus groups were conducted. Most young people defined health solely in terms of their physical well-being, but still identified a broad range of situations, conditions, or behaviors which they believed might affect their health. One-third of females and two-thirds of males said they would not seek help for their health concerns, and when they did, were most likely to seek help from family, friends, or others they trusted. When professional help was sought, young people again preferred someone they knew and trusted. The three groups of barriers to accessing health care were: concerns about confidentiality, knowledge of services and discomfort in disclosing health concerns, and accessibility and characteristics of services. Factors related to use of health care services were associated with age, gender, and location, but rarely with socioeconomic status. CONCLUSIONS: The majority of these young people in New South Wales (particularly males) do not seek health care despite identifying a broad range of issues that affect their health. [ABSTRACT FROM AUTHOR]

The contemporary health problems of young people occur within the context of the physical, social, cultural, economic, and political realities within which they live. There are commonalities and differences in this context among developed and developing countries, thus differing effects on the individual's personal as well as national development. Internationally, the origins and evolution of health care for adolescents can be viewed as an unfolding saga taking place particularly over the past 30 years. It is a story of advocacy and subsequent achievement in all corners of the world. This paper reviews the important developments in the international arena, recognizes major pioneers and milestones, and explores some of the current and future issues facing the field. The authors draw heavily on their experiences with the major nongovernmental adolescent health organizations. The special roles of the World Health Organization, Pan American Health Organization, and United Nations Children's Fund (UNICEF) are highlighted, and special consideration is given to the challenge of inclusion through youth participation. [ABSTRACT FROM AUTHOR]

Background: We investigated the potential impacts of child poverty (CP) reduction scenarios on population health and health inequalities in England between 2024 and 2033., Methods: We combined aggregate local authority-level data with published and newly created estimates on the association between CP and the rate per 100 000 of infant mortality, children (aged <16) looked after, child (aged <16) hospitalisations for nutritional anaemia and child (aged <16) all-cause emergency hospital admissions. We modelled relative, absolute (per 100 000) and total (per total population) annual changes for these outcomes under three CP reduction scenarios between 2024 and 2033- low-ambition (15% reduction), medium-ambition (25% reduction) and high-ambition (35% reduction)-compared with a baseline CP scenario (15% increase). Annual changes were aggregated between 2024 and 2033 at national, regional and deprivation (IMD tertiles) levels to investigate inequalities., Results: All CP reduction scenarios would result in substantial improvements to child health. Meeting the high-ambition reduction would decrease total cases of infant mortality (293; 95% CI 118 to 461), children looked after (4696; 95% CI 1987 to 7593), nutritional anaemia (458, 95% CI 336 to 574) and emergency admissions (32 650; 95% CI 4022 to 61 126) between 2024 and 2033. Northern regions (eg, North East) exhibited the greatest relative and absolute benefit. The most deprived tertile would experience the largest relative, absolute and total benefit; under high-ambition reduction, total infant mortality cases were predicted to fall by 126 (95% CI 51 to 199) in the most deprived tertile compared with 71 (95% CI 29 to 112) in the least between 2024 and 2033., Conclusions: Achieving reductions in CP could substantially improve child health and reduce health inequalities in England., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Abstract: There is a rich literature describing the loss of dorsal root ganglion (DRG) neurons following peripheral axotomy, but the vulnerability of discrete subpopulations has not yet been characterised. Furthermore, the extent or even presence of neuron loss following injury has recently been challenged. In this study, we have used a range of transgenic recombinase driver mouse lines to genetically label molecularly defined subpopulations of DRG neurons and track their survival following traumatic nerve injury. We find that spared nerve injury leads to a marked loss of cells containing DRG volume and a concomitant loss of small-diameter DRG neurons. Neuron loss occurs unequally across subpopulations and is particularly prevalent in nonpeptidergic nociceptors, marked by expression of Mrgprd. We show that this subpopulation is almost entirely lost following spared nerve injury and severely depleted (by roughly 50%) following sciatic nerve crush. Finally, we used an in vitro model of DRG neuron survival to demonstrate that nonpeptidergic nociceptor loss is likely dependent on the absence of neurotrophic support. Together, these results profile the extent to which DRG neuron subpopulations can survive axotomy, with implications for our understanding of nerve injury-induced plasticity and pain., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

About 20% of patients with diabetes suffer from chronic pain with neuropathic characteristics. We investigated the multivariate associations between 92 neurology-related proteins measured in serum from 190 patients with painful and painless diabetic neuropathy. Participants were recruited from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the exploration cohort, two groups were defined by hierarchical cluster analyses of protein data. The proportion of painless vs painful neuropathy did not differ between the two groups, but one group had a significantly higher grade of neuropathy as measured by the Toronto Clinical Scoring System (TCSS). This finding was replicated in the replication cohort. Analyzing both groups together, we found that a group of 11 inter-correlated proteins (TNFRSF12A, SCARB2, N2DL-2, SKR3, EFNA4, LAYN, CLM-1, CD38, UNC5C, GFR-alpha-1, and JAM-B) were positively associated with TCSS values. Notably, EFNA4 and UNC5C are known to be part of axon guidance pathways. To conclude, although cluster analysis of 92 neurology-related proteins did not distinguish painful from painless diabetic neuropathy, we identified 11 proteins which positively correlated to neuropathy severity and warrant further investigation as potential biomarkers., (© 2024. The Author(s).)

Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: It is still unclear how and why some patients develop painful and others painless polyneuropathy. The aim of this study was to identify multiple factors associated with painful polyneuropathies (NeuP). A total of 1181 patients of the multicenter DOLORISK database with painful (probable or definite NeuP) or painless (unlikely NeuP) probable or confirmed neuropathy were investigated clinically, with questionnaires and quantitative sensory testing. Multivariate logistic regression including all variables (demographics, medical history, psychological symptoms, personality items, pain-related worrying, life-style factors, as well as results from clinical examination and quantitative sensory testing) and machine learning was used for the identification of predictors and final risk prediction of painful neuropathy. Multivariate logistic regression demonstrated that severity and idiopathic etiology of neuropathy, presence of chronic pain in family, Patient-Reported Outcomes Measurement Information System Fatigue and Depression T-Score, as well as Pain Catastrophizing Scale total score are the most important features associated with the presence of pain in neuropathy. Machine learning (random forest) identified the same variables. Multivariate logistic regression archived an accuracy above 78%, random forest of 76%; thus, almost 4 out of 5 subjects can be classified correctly. This multicenter analysis shows that pain-related worrying, emotional well-being, and clinical phenotype are factors associated with painful (vs painless) neuropathy. Results may help in the future to identify patients at risk of developing painful neuropathy and identify consequences of pain in longitudinal studies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Objective: To determine the feasibility of standardized, prospective assignment of initial method of detection (MOD) of breast cancer by radiologists in diverse practice settings., Methods: This multicenter, retrospective study analyzed the rate of assignment of MOD in four geographically varied health systems. A universal protocol for basic MOD assignment was agreed upon by the authors before start of the pilot study. Radiologists at each site were instructed how to assign MOD. Charts were then reviewed to determine the frequency and accuracy of MOD assignment for all cases subsequently diagnosed with breast cancer. When available, data regarding frequency of tumor registry abstraction were also reviewed for frequency and accuracy., Results: A total of 2,328 patients with a new diagnosis of breast cancer were evaluated across the sites over the study period. Of these patients, initial MOD was prospectively assigned by the radiologist in 94% of cases. Of the cases in which MOD was assigned, retrospective review confirmed accurate assignment in 96% of cases., Conclusions: Prospective, standardized assignment of initial MOD of breast cancer is feasible across different practice sites and can be accurately captured in tumor registries. Standard collection of MOD would provide critical data about the impact of screening mammography in the United States., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Fibrocystic changes are commonly seen in clinically symptomatic patients and during imaging workup of screening-detected findings. The term "fibrocystic changes" encompasses a broad spectrum of specific benign pathologic entities. Recognition of classically benign findings of fibrocystic changes, including cysts and layering calcifications, can prevent unnecessary follow-ups and biopsies. Imaging findings such as solid masses, nonlayering calcifications, and architectural distortion may require core needle biopsy for diagnosis. In these cases, understanding the varied appearances of fibrocystic change aids determination of radiologic-pathologic concordance. Management of fibrocystic change is typically conservative., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Early detection of breast cancer from regular screening substantially reduces breast cancer mortality and morbidity. Multiple different imaging modalities may be used to screen for breast cancer. Screening recommendations differ based on an individual's risk of developing breast cancer. Numerous factors contribute to breast cancer risk, which is frequently divided into three major categories: average, intermediate, and high risk. For patients assigned female at birth with native breast tissue, mammography and digital breast tomosynthesis are the recommended method for breast cancer screening in all risk categories. In addition to the recommendation of mammography and digital breast tomosynthesis in high-risk patients, screening with breast MRI is recommended. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids., (© 2024. The Author(s).)

Purpose: The impact of opportunistic screening mammography in the United States is difficult to quantify, partially due to lack of inclusion regarding method of detection (MOD) in national registries. This study sought to determine the feasibility of MOD collection in a multicenter community registry and to compare outcomes and characteristics of breast cancer based on MOD., Methods: We conducted a retrospective study of breast cancer patients from a multicenter tumor registry in Missouri from January 2004 - December 2018. Registry data were extracted by certified tumor registrars and included MOD, clinicopathologic information, and treatment. MOD was assigned as screen-detected or clinically detected. Data were analyzed at the patient level. Chi-squared tests were used for categorical variable comparison and Mann-Whitney-U test was used for numerical variable comparison., Results: 5351 women (median age, 63 years; interquartile range, 53-73 years) were included. Screen-detected cancers were smaller than clinically detected cancers (median size 12 mm vs. 25 mm; P < .001) and more likely node-negative (81% vs. 54%; P < .001), lower grade (P < .001), and lower stage (P < .001). Screen-detected cancers were more likely treated with lumpectomy vs. mastectomy (73% vs. 41%; P < .001) and less likely to require chemotherapy (24% vs. 52%; P < .001). Overall survival for patients with invasive breast cancer was higher for screen-detected cancers (89% vs. 74%, P < .0001)., Conclusion: MOD can be routinely collected and linked to breast cancer outcomes through tumor registries, with demonstration of significant differences in outcome and characteristics of breast cancers based on MOD. Routine inclusion of MOD in US tumor registries would help quantify the impact of opportunistic screening mammography in the US., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a "high-level" endocannabinoid group and a "low-level" group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group ( P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Purpose: Accurate pectoral muscle removal is critical in mammographic breast density estimation and many other computer-aided algorithms. We propose a novel approach to remove pectoral muscles form mediolateral oblique (MLO) view mammograms and compare accuracy and computational efficiency with existing method (Libra)., Methods: A pectoral muscle identification pipeline was developed. The image is first binarized to enhance contrast and then the Canny algorithm was applied for edge detection. Robust interpolation is used to smooth out the pectoral muscle region. Accuracy and computational speed of pectoral muscle identification was assessed using 951 women (1,902 MLO mammograms) from the Joanne Knight Breast Health Cohort at Washington University School of Medicine., Results: Our proposed algorithm exhibits lower mean error of 12.22% in comparison to Libra's estimated error of 20.44%. This 40% gain in accuracy was statistically significant (p < 0.001). The computational time for the proposed algorithm is 5.4 times faster when compared to Libra (5.1 s for proposed vs. 27.7 s for Libra per mammogram)., Conclusion: We present a novel approach for pectoral muscle removal in mammogram images that demonstrates significant improvement in accuracy and efficiency compared to existing method. Our findings have important implications for the development of computer-aided systems and other automated tools in this field., (© 2023. The Author(s).)

Background: Peripheral nerve biopsy is a valuable final diagnostic tool; however, histopathological results can be non-diagnostic., Aims: We aim to identify quality improvement measures by evaluating the pre-biopsy assessment and diagnostic yield of specific histopathological diagnosis., Methods: This was a retrospective study based on 10 years of experience with peripheral nerve biopsies at a single centre. Clinical data were obtained regarding pre-biopsy history, examination, serum and cerebrospinal fluid (CSF) investigations, neurophysiology and peripheral nerve imaging. Based upon a histopathological outcome, patients were grouped into vasculitis, granulomatous and infiltrative (diagnostic) group, or a comparison group of non-specific axonal neuropathy and normal (non-specific/normal) group., Results: From a cohort of 64 patients, 21 (32.8%) were included in the diagnostic group and 30 (46.9%) in the non-specific/normal group. Clinical parameters associated with the diagnostic group were shorter history (mean 10.2 months vs 38.1), stepwise progression (81% vs 20%), neuropathic pain (85.7% vs 56.7%), vasculitic rash (23.8% vs 0%), mononeuritis multiplex (57.1% vs 10%), asymmetry (90.5% vs 60%), raised white cell count (47.6% vs 16.7%), myeloperoxidase antibody (19.1% vs 0%) and abnormal peripheral nerve imaging (33.3% vs 10%)., Conclusion: Selection of patients undergoing nerve biopsy requires careful consideration of clinical parameters, including peripheral nerve imaging. Several quality improvement measures are proposed to improve yield of clinically actionable information from nerve biopsy., (© 2023 Royal Australasian College of Physicians.)

Abstract: Insight into nociceptive circuits will ultimately build our understanding of pain processing and aid the development of analgesic strategies. Neural circuit analysis has been advanced greatly by the development of optogenetic and chemogenetic tools, which have allowed function to be ascribed to discrete neuronal populations. Neurons of the dorsal root ganglion, which include nociceptors, have proved challenging targets for chemogenetic manipulation given specific confounds with commonly used DREADD technology. We have developed a cre/lox dependant version of the engineered glutamate-gated chloride channel (GluCl) to restrict and direct its expression to molecularly defined neuronal populations. We have generated GluCl.Cre ON that selectively renders neurons expressing cre-recombinase susceptible to agonist-induced silencing. We have functionally validated our tool in multiple systems in vitro, and subsequently generated viral vectors and tested its applicability in vivo. Using Nav1.8 Cre mice to restrict AAV-GluCl.Cre ON to nociceptors, we demonstrate effective silencing of electrical activity in vivo and concomitant hyposensitivity to noxious thermal and noxious mechanical pain, whereas light touch and motor function remained intact. We also demonstrated that our strategy can effectively silence inflammatory-like pain in a chemical pain model. Collectively, we have generated a novel tool that can be used to selectively silence defined neuronal circuits in vitro and in vivo. We believe that this addition to the chemogenetic tool box will facilitate further understanding of pain circuits and guide future therapeutic development., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome., Methods: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants., Results: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving., Conclusions: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing., (© 2023. Crown.)