Pathogenesis and Transmission Assessment of 3 Swine-Origin Influenza A(H3N2) Viruses With Zoonotic Risk to Humans Isolated in the United States, 2017-2020.

The sporadic occurrence of human infections with swine-origin influenza A(H3N2) viruses and the continual emergence of novel A(H3N2) viruses in swine herds underscore the necessity for ongoing assessment of the pandemic risk posed by these viruses. Here, we selected 3 recent novel swine-origin A(H3N2) viruses isolated between 2017 to 2020, bearing hemagglutinins from the 1990.1, 2010.1, or 2010.2 clades, and evaluated their ability to cause disease and transmit in a ferret model. We conclude that despite considerable genetic variances, all 3 contemporary swine-origin A(H3N2) viruses displayed a capacity for robust replication in the ferret respiratory tract and were also capable of limited airborne transmission. These findings highlight the continued public health risk of swine-origin A(H3N2) strains, especially in human populations with low cross-reactive immunity.

Comprehensive assessment of TDP-43 neuropathology data in the National Alzheimer's Coordinating Center database.

TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer's Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%). Regional TDP-43 pathologic assessment was available for 77% of participants, with hippocampus the most common region. Availability for the TDP-43-related measures increased over time, and was higher in centers with high proportions of participants with clinical FTLD. Part II: In 2142 participants with all TDP-43-related assessments available, 27% of participants had LATE-NC, whereas ALS-TDP or FTLD-TDP (ALS/FTLD-TDP) was present in 9% of participants, and 2% of participants had TDP-43 related to other pathologies ("Other TDP-43"). HS-A was present in 14% of participants, of whom 55% had LATE-NC, 20% ASL/FTLD-TDP, 3% Other TDP-43, and 23% no TDP-43. LATE-NC, ALS/FTLD-TDP, and Other TDP-43, were each associated with higher odds of dementia, HS-A, and hippocampal atrophy, compared to those without TDP-43 pathology. LATE-NC was associated with higher odds for Alzheimer's disease (AD) clinical diagnosis, AD neuropathologic change (ADNC), Lewy bodies, arteriolosclerosis, and cortical atrophy. ALS/FTLD-TDP was associated with higher odds of clinical diagnoses of primary progressive aphasia and behavioral-variant frontotemporal dementia, and cortical/frontotemporal lobar atrophy. When using NACC data for TDP-43-related analyses, researchers should carefully consider the incomplete availability of the different regional TDP-43 assessments, the high frequency of participants with ALS/FTLD-TDP, and the presence of other forms of TDP-43 pathology.

Postherpetic granulomatous dermatitis occurring in the setting of immune checkpoint inhibitor therapy: A case report.

We report a case of a 72-year-old man presenting with a 2-month history of a persistent, painful rash of the chest, axilla, and back. He had a history of recently resolved varicella zoster virus reactivation in the same distribution of the current rash and metastatic malignant melanoma treated with nivolumab and ipilimumab. The histopathology was consistent with granulomatous dermatitis (GD), and a diagnosis of postherpetic isotopic response manifesting as GD was made. Given the paucity of reported cases of postherpetic GD in the setting of treatment with immune checkpoint inhibitors (ICIs), we discuss the clinicopathologic features of this case and potential mechanisms by which ICIs may contribute to the development of granulomatous disease.

Characterization of hippocampal sclerosis of aging and its association with other neuropathologic changes and cognitive deficits in the oldest-old.

Hippocampal sclerosis of aging (HS-A) is a common age-related neuropathological lesion characterized by neuronal loss and astrogliosis in subiculum and CA1 subfield of hippocampus. HS-A is associated with cognitive decline that mimics Alzheimer's disease. Pathological diagnosis of HS-A is traditionally binary based on presence/absence of the lesion. We compared this traditional measure against our novel quantitative measure for studying the relationship between HS-A and other neuropathologies and cognitive impairment. We included 409 participants from The 90+ study with neuropathological examination and longitudinal neuropsychological assessments. In those with HS-A, we examined digitized H&E and LFB stained hippocampal slides. The length of HS-A in each subfield of hippocampus and subiculum, each further divided into three subregions, was measured using Aperio eSlide Manager. For each subregion, the proportion affected by HS-A was calculated. Using regression models, both traditional/binary and quantitative measures were used to study the relationship between HS-A and other neuropathological changes and cognitive outcomes. HS-A was present in 48 (12%) of participants and was always focal, primarily affecting CA1 (73%), followed by subiculum (9%); overlapping pathology (subiculum and CA1) affected 18% of individuals. HS-A was more common in the left (82%) than the right (25%) hemisphere and was bilateral in 7% of participants. HS-A traditional/binary assessment was associated with limbic-predominant age-related TDP-43 encephalopathy (LATE-NC; OR = 3.45, p < 0.001) and aging-related tau astrogliopathy (ARTAG; OR = 2.72, p = 0.008). In contrast, our quantitative approach showed associations between the proportion of HS-A (CA1/subiculum/combined) and LATE-NC (p = 0.001) and arteriolosclerosis (p = 0.005). While traditional binary assessment of HS-A was associated with impaired memory (OR = 2.60, p = 0.007), calculations (OR = 2.16, p = 0.027), and orientation (OR = 3.56, p < 0.001), our quantitative approach revealed additional associations with impairments in language (OR = 1.33, p = 0.018) and visuospatial domains (OR = 1.37, p = 0.006). Our novel quantitative method revealed associations between HS-A and vascular pathologies and impairment in cognitive domains that were not detected using traditional/binary measures.

Erratum: Measurement of the 2νßß Decay Half-Life of

This corrects the article DOI: 10.1103/PhysRevLett.126.171801.

Enterprise risk management for automation in correctional facilities with pandemic and other stressors.

Real-time tracking of tool and equipment inventories is a critical function of many organizations and sectors. For prisons and correctional facilities, tracking and monitoring of assets such as cookware, hardware, keys, janitorial equipment, vocational/technical specialty tools, etc., is essential for safety, security, trust, efficiency, education, etc. The performance of automated systems for this purpose can be diminished by a variety of emergent and future sociotechnical factors alone and in combination. This article introduces a methodology for contractor evaluation and selection in acquisition of innovative asset management systems, with an emphasis on evolving system requirements under uncertainty. The methodology features a scenario-based preferences analysis of emergent and future conditions that are disruptive to the performance of the asset-control system. The conditions are across technologies, operating environments, regulations, workforce behaviors, offender behaviors, prices and markets, organizations, cyber threats, etc. The methodology addresses the influence and interaction of the conditions to disrupt system priorities. Examples include: (i) infectious disease disrupting priorities among requirements and (ii)  radio-frequency identification (RFID) and wireless-technology innovations disrupting priorities among stakeholders. The combinations of conditions that most and least matter for the system acquisition are characterized. The methodology constitutes a risk register for monitoring sources of risk to project performance, schedule, and cost throughout the system lifecycle. The results will be of interest to both practitioners and scholars engaged in systems acquisition as the pandemic interacts with other factors to affect risk, uncertainty, and resilience of organizational missions and operations.

Role of primary cilia and Hedgehog signaling in craniofacial features of Ellis-van Creveld syndrome.

Ellis-van Creveld syndrome (EvC) is an autosomal recessive genetic disorder involving pathogenic variants of EVC and EVC2 genes and classified as a ciliopathy. The syndrome is caused by mutations in the EVC gene on chromosome 4p16, and EVC2 gene, located close to the EVC gene, in a head-to-head configuration. Regardless of the affliction of EVC or EVC2, the clinical features of Ellis-van Creveld syndrome are similar. Both these genes are expressed in tissues such as, but not limited to, the heart, liver, skeletal muscle, and placenta, while the predominant expression in the craniofacial tissues is that of EVC2. Biallelic mutations of EVC and EVC2 affect Hedgehog signaling and thereby ciliary function, crucial factors in vertebrate development, culminating in the phenotypical features characteristic of EvC. The clinical features of Ellis-van Creveld syndrome are consistent with significant abnormalities in morphogenesis and differentiation of the affected tissues. The robust role of primary cilia in histodifferentiation and morphodifferentiation of oral, perioral, and craniofacial tissues is becoming more evident in the most recent literature. In this review, we give a summary of the mechanistic role of primary cilia in craniofacial development, taking Ellis-van Creveld syndrome as a representative example.

Determination of the

We report the first measurement of the parity-violating elastic electron scattering asymmetry on ^{27}Al. The ^{27}Al elastic asymmetry is A_{PV}=2.16±0.11(stat)±0.16(syst) ppm, and was measured at ⟨Q^{2}⟩=0.02357±0.00010 GeV^{2}, ⟨θ_{lab}⟩=7.61°±0.02°, and ⟨E_{lab}⟩=1.157 GeV with the Q_{weak} apparatus at Jefferson Lab. Predictions using a simple Born approximation as well as more sophisticated distorted-wave calculations are in good agreement with this result. From this asymmetry the ^{27}Al neutron radius R_{n}=2.89±0.12 fm was determined using a many-models correlation technique. The corresponding neutron skin thickness R_{n}-R_{p}=-0.04±0.12 fm is small, as expected for a light nucleus with a neutron excess of only 1. This result thus serves as a successful benchmark for electroweak determinations of neutron radii on heavier nuclei. A tree-level approach was used to extract the ^{27}Al weak radius R_{w}=3.00±0.15 fm, and the weak skin thickness R_{wk}-R_{ch}=-0.04±0.15 fm. The weak form factor at this Q^{2} is F_{wk}=0.39±0.04.

Trigeminal Traumatic Neuroma: a Comprehensive Review of the Literature Based On a Rare Case.

PURPOSE OF REVIEW: Traumatic neuromas in general, and trigeminal traumatic neuromas in particular, are relatively rare entities originating from a damage to a corresponding nerve or its branches. This manuscript is a comprehensive review of the literature on trigeminal traumatic neuromas based on an interesting and challenging case of bilateral intraoral lesions. RECENT FINDINGS: The diagnosis for this patient was bilateral trigeminal traumatic neuromas. It is possible that these patients have a genetic predisposition to the development of these lesions. It is a neuropathic pain condition and may mimic dental and other trigeminal pain entities. Topical treatment with lidocaine gel, utilizing a custom-made neurosensory stent, rendered the patient significant and sustained pain relief. Trigeminal traumatic neuromas present a diagnostic challenge even to a seasoned clinician, due to the complex clinical features that may mimic other entities. Topical medications such as local anesthetics may be a good viable alternative to systemic medications to manage the pain associated with the condition. Early identification of the lesion and the associated pain helps in the succinct management of symptomatic trigeminal traumatic neuromas.

Giant Cell Arteritis: A Case-Based Narrative Review of the Literature.

PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a chronic, inflammatory condition, primarily affecting the medium and larger arteries. The purpose of this narrative review is to describe GCA in the context of headache and facial pain, based on a case and the available current literature. Understanding the etiology, pathophysiology, the associated conditions, and the differential diagnoses is important in managing GCA. RECENT FINDINGS: In a patient presenting with unilateral facial/head pain with disturbances of vision, GCA should be considered in the differential diagnosis. There is an association of GCA with several comorbid conditions, and infections including coronavirus-19 (COVID-19) infection. Management of GCA primarily depends upon the identification of the affected artery and prompt treatment. Permanent visual loss and other serious complications are associated with GCA. GCA is characterized by robust inflammation of large- and medium-sized arteries and marked elevation of systemic mediators of inflammation. An interdisciplinary approach of management involving the pertinent specialties is strongly recommended.

Veno-arteriovenous (V-AV) ECMO configuration: A single-center experience.

BACKGROUND: With increasing extracorporeal membrane oxygenation (ECMO) utilization over the last decade, clinicians have developed "hybrid" configurations to meet complex perfusion requirements. In the setting of differential hypoxemia, a veno-arteriovenous (V-AV) configuration provides oxygenated cardiac preload and hemodynamic support to satisfy physiologic demands. We aim to further characterize the patient population, indications, and outcomes associated with this hybrid configuration. METHODS: We retrospectively reviewed all adult patients placed on V-AV ECMO at our institution from June 2016 to December 2019. Through a review of the electronic medical records, data describing demographic features, comorbidities, and ECMO-specific information were analyzed systematically. RESULTS: 14 patients were placed on V-AV ECMO during the study period. Our cohort was 79% male with a median age of 54 and BMI of 30.3. These patients had a median SOFA-0 score of 15 and SAVE score of -12. Patients were treated with ECMO support for a median of 144.1 (IQR 98.5 - 183.1) hours, consisting of 0.2 (IQR 0 - 17.7) hours of VA and 92.4 (IQR 53.7 - 115.1) hours of V-AV followed by 67.4 (IQR 20.3 - 96.6) hours of VV support. Of these 14 patients, 11 survived to decannulation (79%) and 9 survived to hospital discharge (64%). CONCLUSION: ECMO patients with recovering left ventricular function and persistent gas exchange abnormalities are at risk for developing differential hypoxemia. We describe an approach to utilizing V-AV configuration when the likelihood of differential hypoxemia is extremely high, with a survival rate that compares favorably to Extracorporeal Life Support Organization statistics and published case series.

Detection and Characterization of Swine Origin Influenza A(H1N1) Pandemic 2009 Viruses in Humans following Zoonotic Transmission.

Human-to-swine transmission of seasonal influenza viruses has led to sustained human-like influenza viruses circulating in the U.S. swine population. While some reverse zoonotic-origin viruses adapt and become enzootic in swine, nascent reverse zoonoses may result in virus detections that are difficult to classify as "swine-origin" or "human-origin" due to the genetic similarity of circulating viruses. This is the case for human-origin influenza A(H1N1) pandemic 2009 (pdm09) viruses detected in pigs following numerous reverse zoonosis events since the 2009 pandemic. We report the identification of two human infections with A(H1N1)pdm09 viruses originating from swine hosts and classify them as "swine-origin" variant influenza viruses based on phylogenetic analysis and sequence comparison methods. Phylogenetic analyses of viral genomes from two cases revealed these viruses were reassortants containing A(H1N1)pdm09 hemagglutinin (HA) and neuraminidase (NA) genes with genetic combinations derived from the triple reassortant internal gene cassette. Follow-up investigations determined that one individual had direct exposure to swine in the week preceding illness onset, while another did not report swine exposure. The swine-origin A(H1N1) variant cases were resolved by full genome sequence comparison of the variant viruses to swine influenza genomes. However, if reassortment does not result in the acquisition of swine-associated genes and swine virus genomic sequences are not available from the exposure source, future cases may not be discernible. We have developed a pipeline that performs maximum likelihood analyses, a k-mer-based set difference algorithm, and random forest algorithms to identify swine-associated sequences in the hemagglutinin gene to differentiate between human-origin and swine-origin A(H1N1)pdm09 viruses.IMPORTANCE Influenza virus infects a wide range of hosts, resulting in illnesses that vary from asymptomatic cases to severe pneumonia and death. Viral transfer can occur between human and nonhuman hosts, resulting in human and nonhuman origin viruses circulating in novel hosts. In this work, we have identified the first case of a swine-origin influenza A(H1N1)pdm09 virus resulting in a human infection. This shows that these viruses not only circulate in swine hosts, but are continuing to evolve and distinguish themselves from previously circulating human-origin influenza viruses. The development of techniques for distinguishing human-origin and swine-origin viruses are necessary for the continued surveillance of influenza viruses. We show that unique genetic signatures can differentiate circulating swine-associated strains from circulating human-associated strains of influenza A(H1N1)pdm09, and these signatures can be used to enhance surveillance of swine-origin influenza.

Genetically and Antigenically Divergent Influenza A(H9N2) Viruses Exhibit Differential Replication and Transmission Phenotypes in Mammalian Models.

Low-pathogenicity avian influenza A(H9N2) viruses, enzootic in poultry populations in Asia, are associated with fewer confirmed human infections but higher rates of seropositivity compared to A(H5) or A(H7) subtype viruses. Cocirculation of A(H5) and A(H7) viruses leads to the generation of reassortant viruses bearing A(H9N2) internal genes with markers of mammalian adaptation, warranting continued surveillance in both avian and human populations. Here, we describe active surveillance efforts in live poultry markets in Vietnam in 2018 and compare representative viruses to G1 and Y280 lineage viruses that have infected humans. Receptor binding properties, pH thresholds for HA activation, in vitro replication in human respiratory tract cells, and in vivo mammalian pathogenicity and transmissibility were investigated. While A(H9N2) viruses from both poultry and humans exhibited features associated with mammalian adaptation, one human isolate from 2018, A/Anhui-Lujiang/39/2018, exhibited increased capacity for replication and transmission, demonstrating the pandemic potential of A(H9N2) viruses.IMPORTANCE A(H9N2) influenza viruses are widespread in poultry in many parts of the world and for over 20 years have sporadically jumped species barriers to cause human infection. As these viruses continue to diversify genetically and antigenically, it is critical to closely monitor viruses responsible for human infections, to ascertain if A(H9N2) viruses are acquiring properties that make them better suited to infect and spread among humans. In this study, we describe an active poultry surveillance system established in Vietnam to identify the scope of influenza viruses present in live bird markets and the threat they pose to human health. Assessment of a recent A(H9N2) virus isolated from an individual in China in 2018 is also reported, and it was found to exhibit properties of adaptation to humans and, importantly, it shows similarities to strains isolated from the live bird markets of Vietnam.

Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).

BACKGROUND: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. OBJECTIVES: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. METHODS: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40-80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0-100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. RESULTS: 64 adults (54 females, 10 males) aged 48-79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. CONCLUSIONS: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Measurement of the 2νßß Decay Half-Life of

We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20} yr. This measurement is the most precise determination of the ^{130}Te 2νßß decay half-life to date.

Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic - United States, 2020-2021.

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.

Process and Outcome Evaluation of a Mindfulness-Based Cognitive Therapy Intervention for Cisgender and Transgender African American Women Living with HIV/AIDS.

There is a need for evidence-based contextualized mental health interventions for persons living with HIV/AIDS. In the current study, the primary researcher conducted open trials with African American women living with HIV/AIDS (AAWLWHA) to examine the acceptability and feasibility of Project UPLIFT, a mindfulness-based cognitive therapy intervention that has demonstrated effectiveness in persons living with epilepsy. Women were recruited for a tele-delivered phone intervention group separated by gender identity, as well as participated in pre- and post-test assessments. Additionally, data on acceptability was collected. Both cis- and transgender women were highly satisfied with the intervention and demonstrated improvement in depressive and stress symptoms. The intervention seemed to be particularly feasible for cisgender women, though more qualitative mental health research may be warranted with transgender women. The current research has implications for the utility of mindfulness-based interventions such as UPLIFT, with AAWLWHA.

Breast Cancer Staging: Updates in the AJCC Cancer Staging Manual, 8th Edition, and Current Challenges for Radiologists, From the AJR Special Series on Cancer Staging.

The standardization of the AJCC TNM staging system for breast cancer allows physicians to evaluate patients with breast cancer using standard language and criteria, assess treatment response, and compare patient outcomes. Previous editions of the AJCC Cancer Staging Manual relied on the anatomic TNM method of staging that incorporates imaging and uses population-level survival data to predict patient outcomes. Recent advances in therapy based on biomarker status and multigene panels have improved treatment strategies. In the newest edition of the AJCC Cancer Staging Manual (8th edition, adopted on January 1, 2018), breast cancer staging integrates anatomic staging with tumor grade, biomarker data regarding hormone receptor status, oncogene expression, and gene expression profiling to assign a prognostic stage. This article reviews the 8th edition of the AJCC breast cancer staging system with a focus on anatomic staging and the challenges that anatomic staging poses for radiologists. We highlight key imaging findings that impact patient treatment and discuss the role of imaging in evaluating response to neoadjuvant therapy. Finally, we discuss biomarkers and multigene panels and how these impact prognostic stage. The review will help radiologists identify critical findings that affect breast cancer staging and understand ongoing limitations of imaging in staging.