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Abstract Background An isolate originally labeled Bacillus megaterium CDC 684 was found to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and produced both the protective antigen and the poly-D-glutamic acid capsule. These phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify this isolate to Bacillus anthracis in 1990. Results We demonstrate that despite these B. anthracis features, the isolate is severely attenuated in a guinea pig model. This prompted whole genome sequencing and closure. The comparative analysis of CDC 684 to other sequenced B. anthracis isolates and further analysis reveals: a) CDC 684 is a close relative of a virulent strain, Vollum A0488; b) CDC 684 defines a new B. anthracis lineage (at least 51 SNPs) that includes 15 other isolates; c) the genome of CDC 684 contains a large chromosomal inversion that spans 3.3 Mbp; d) this inversion has caused a displacement of the usual spatial orientation of the origin of replication (ori) to the termination of replication (ter) from 180° in wild-type B. anthracis to 120° in CDC 684 and e) this isolate also has altered growth kinetics in liquid media. Conclusions We propose two alternative hypotheses explaining the attenuated phenotype of this isolate. Hypothesis 1 suggests that the skewed ori/ter relationship in CDC 684 has altered its DNA replication and/or transcriptome processes resulting in altered growth kinetics and virulence capacity. Hypothesis 2 suggests that one or more of the single nucleotide polymorphisms in CDC 684 has altered the expression of a regulatory element or other genes necessary for virulence.

Abstract Background Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. Results Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. Conclusion We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer.

Abstract Background Single nucleotide polymorphisms (SNPs) and genes that exhibit presence/absence variation have provided informative marker sets for bacterial and viral genotyping. Identification of marker sets optimised for these purposes has been based on maximal generalized discriminatory power as measured by Simpson's Index of Diversity, or on the ability to identify specific variants. Here we describe the Not-N algorithm, which is designed to identify small sets of genetic markers diagnostic for user-specified subsets of known genetic variants. The algorithm does not treat the user-specified subset and the remaining genetic variants equally. Rather Not-N analysis is designed to underpin assays that provide 0% false negatives, which is very important for e.g. diagnostic procedures for clinically significant subgroups within microbial species. Results The Not-N algorithm has been incorporated into the "Minimum SNPs" computer program and used to derive genetic markers diagnostic for multilocus sequence typing-defined clonal complexes, hepatitis C virus (HCV) subtypes, and phylogenetic clades defined by comparative genome hybridization (CGH) data for Campylobacter jejuni, Yersinia enterocolitica and Clostridium difficile. Conclusion Not-N analysis is effective for identifying small sets of genetic markers diagnostic for microbial sub-groups. The best results to date have been obtained with CGH data from several bacterial species, and HCV sequence data.

We report 2 canine cases of carbapenemase-producing Pseudomonas aeruginosa within a United States veterinary hospital associated with a human outbreak linked to over-the-counter artificial tears. We investigated veterinary hospital transmission. Veterinary antimicrobial resistance surveillance and infection prevention and control enhancements are needed to reduce transmission of carbapenemase-producing organisms.

Background: This multicenter and retrospective study investigated the additive value of tumor morphologic features derived from the functional tumor volume (FTV) tumor mask at pre-treatment (T0) and the early treatment time point (T1) in the prediction of pathologic outcomes for breast cancer patients undergoing neoadjuvant chemotherapy., Methods: A total of 910 patients enrolled in the multicenter I-SPY 2 trial were included. FTV and tumor morphologic features were calculated from the dynamic contrast-enhanced (DCE) MRI. A poor response was defined as a residual cancer burden (RCB) class III (RCB-III) at surgical excision. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive performance. The analysis was performed in the full cohort and in individual sub-cohorts stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status., Results: In the full cohort, the AUCs for the use of the FTV ratio and clinicopathologic data were 0.64 ± 0.03 (mean ± SD [standard deviation]). With morphologic features, the AUC increased significantly to 0.76 ± 0.04 ( p < 0.001). The ratio of the surface area to volume ratio between T0 and T1 was found to be the most contributing feature. All top contributing features were from T1. An improvement was also observed in the HR+/HER2- and triple-negative sub-cohorts. The AUC increased significantly from 0.56 ± 0.05 to 0.70 ± 0.06 ( p < 0.001) and from 0.65 ± 0.06 to 0.73 ± 0.06 ( p < 0.001), respectively, when adding morphologic features., Conclusion: Tumor morphologic features can improve the prediction of RCB-III compared to using FTV only at the early treatment time point.

Rabies is a fatal encephalitic disease affecting all mammals. This report describes identification of raccoon rabies virus variant isolated from a stray kitten in an urban Midwestern city that is nonendemic for this virus variant. The kitten originally presented with nonspecific neurologic abnormalities. Astute veterinary, wildlife, and public health professionals played a critical role in the identification of this fatal zoonotic disease and the extensive public health and wildlife management response that ensued. This case serves as an important reminder of the risk of rabies in unvaccinated animals or those without known vaccination status, including stray animals.

The aging eye undergoes the same progressive crosslinking which occurs throughout the body, resulting in increased rigidity of ocular connective tissues including the lens and the sclera which impact ocular functions. This offers the potential for a scleral treatment that is based on restoring normal biomechanical movements. Laser Scleral Microporation is a laser therapy that evaporates fractional areas of crosslinked tissues in the sclera, reducing ocular rigidity over critical anatomical zones of the accommodation apparatus, restoring the natural dynamic range of focus of the eye. Although controversial and challenged, an alternative theory for presbyopia is Schachar's theory that suggests a reduction in the space between the ciliary processes and the crystalline lens. Widening of this space with expansion bands has been shown to aid near vision in people with presbyopia, a technique that has been used in the past but seems to be obsolete now. The use of drugs has been used in the treatment of presbyopia, either to cause pupil miosis to increase depth of focus, or an alteration in refractive error (to induce myopia in one eye to create monovision). Drugs and laser ablation of the crystalline lens have been used with the aim of softening the hardened lens. Poor nutrition and excess exposure to ultraviolet light have been implicated in the onset of presbyopia. Dietary nutritional supplements, lifestyle changes have also been shown to improve accommodation and the question arises whether these could be harnessed in a treatment for presbyopia as well., Competing Interests: Declaration of competing interest Shehzad A. Naroo has received unrestricted grant funding from Lenstec, Teleon Surgical and Topcon Europe. Craig Woods is a paid consultant for Brien Holden Vision Institute and Zeiss Vision Care. Raquel Gil-Cazorla has received unrestricted grant funding from Lenstec. AnnMarie Hipsley, Edwin R. Price, Robert E. Ang, and Mitchell A. Jackson, are consultants for Ace Vision Group, Inc. James S. Wolffsohn has received grant funding from Alcon and Rayner, and is a paid consultant for Atia Vision, Bausch + Lomb and Alcon. Marianna Collazos, Frank Eperjesi and Michel Guillon have declared no financial interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the utility of digital mammography in detecting asymptomatic malignancy in autologous flap reconstructions after mastectomy., Methods: A retrospective database review identified all mammograms performed on asymptomatic patients with flap reconstructions over a 9-year period (1/1/2009 to 12/31/2017). A negative examination was defined as BI-RADS 1 or 2 and a positive examination was defined as BI-RADS 0, 4, or 5 assigned to the mastectomy side. Malignant outcomes were determined by pathology results. Interval cancers, or false negatives, were defined as locoregional malignant diagnosis within one year of a negative mammogram. Sensitivity, specificity, predictive values, abnormal interpretation rate, and cancer detection rate were calculated., Results: 626 mammograms of asymptomatic flap reconstructions were performed in 183 patients. The most common flap type was TRAM (83.5 %, 523/626) and DIEP (13.4 %, 84/626). Most exams (98.2 %, 615/626) were negative, assessed as BI-RADS 1 or 2, with no interval cancers at follow-up. Eleven exams (1.8 %, 11/626) were positive, assessed as BI-RADS 0, 4, or 5. After diagnostic work-up of all BI-RADS 0 exams, 9 cases had a final recommendation for biopsy of which 3 were malignant. Mammography yielded a cancer detection rate of 0.5 % (3/626), abnormal interpretation rate of 1.8 % (11/626), NPV of 100 % (615/615), overall PPV of 27.3 % (3/11), PPV2 (positive predictive value of a biopsy recommendation) of 33.3 % (3/9), sensitivity of 100 % (3/3), and specificity of 98.7 % (615/623)., Conclusion: Digital mammography of asymptomatic autologous flap reconstructions after mastectomy demonstrated high sensitivity and low abnormal interpretation rate. Cancer detection rate was comparable to current national benchmarks for mammographic screening in the general U.S. population without mastectomy., Competing Interests: Declaration of competing interest The authors report no relevant disclosures or conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen time points relative to baseline (∆FTV1 and ∆FTV2, respectively) were classified into high-standard or standard groups based on visual assessment of FTV under- and overestimation. Logistic regression models predicting pCR using single predictors (FTV0, ∆FTV1, and ∆FTV2) and multiple predictors (all three) were developed using bootstrap resampling with out-of-sample data evaluation with the area under the receiver operating characteristic curve (AUC) independently in each group. Results This study included 432 women (mean age, 49.0 years ± 10.6 [SD]). In the FTV0 model, the high-standard and standard groups showed similar AUCs (0.61 vs 0.62). The high-standard group had a higher estimated AUC compared with the standard group in the ∆FTV1 (0.74 vs 0.63), ∆FTV2 (0.79 vs 0.62), and multiple predictor models (0.85 vs 0.64), with a statistically significant difference for the latter two models ( P = .03 and P = .01, respectively). Conclusion The findings in this study suggest that longitudinal variation in FTV estimation needs to be considered when using early FTV change as an MRI-based criterion for breast cancer treatment personalization. Keywords: Breast, Cancer, Dynamic Contrast-enhanced, MRI, Tumor Response ClinicalTrials.gov registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Ram in this issue.

Background: In Canada, Indigenous Peoples continue to experience persistent health inequities, resulting in disproportionately poorer health outcomes compared with non-Indigenous Canadians. This study engaged Indigenous patients accessing health care in Vancouver, Canada, about their experiences of racism and improving cultural safety within health care., Methods: A research team consisting of Indigenous and non-Indigenous researchers committed to employing a Two-Eyed Seeing approach and conducting culturally safe research hosted 2 sharing circles in May 2019 with Indigenous people recruited from urban health care settings. Talking circles were led by Indigenous Elders, and thematic analysis was used to identify overarching themes., Results: A total of 26 participants attended 2 sharing circles, which included 25 self-identifying women and 1 self-identifying man. Thematic analysis resulted in the identification of 2 major themes: negative experiences in health care and perspectives on promising health care practices. For the first major theme, subthemes included the following: experiences of racism lead to poorer care experiences and health outcomes, Indigenous-specific racism results in mistrust in the health care system, and participants experience discrediting of traditional medicine and Indigenous perspectives on health. For the second major theme, subthemes included the following: Indigenous-specific services and supports improve trust in health care, Indigenous cultural safety education is necessary for all health care-involved staff, and providing welcoming, Indigenized spaces for Indigenous patients encourages health care engagement., Interpretation: Despite participants' racist health care experiences, receiving culturally safe care was credited with improving trust in the health care system and well-being. The continued expansion of Indigenous cultural safety education, the creation of welcoming spaces, recruitment of Indigenous staff, and Indigenous self-determination over health care services can improve Indigenous patients' health care experiences., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

A data set was constructed consisting of 3021 mass spectra randomly selected from all available families in the ForeST© (Forensic Spectra of Trees) database of mass spectra for wood analyzed by Direct Analysis in Real Time ionization coupled with time-of-flight mass spectrometry (DART-TOFMS). Clear and reproducible differences were observed between the lignin peaks for hardwood angiosperms and coniferous gymnosperms, with DART-TOFMS spectra of angiosperms showing significantly higher relative abundances for peaks associated with syringyl subunits. Application of the method to processed wood samples demonstrated that these differences can be used to provide support for enforcing trade laws by accurately identifying the source of finished wood products from hardwood angiosperms and coniferous gymnosperms.

Purpose: To examine the ocular changes in accommodation, wavefront aberrations, and dynamic range of focus (DROF) after laser scleral microporation (LSM) for treating presbyopia., Methods: Four presbyopic aged cynomolgus macaques (>13 years; n = 8 eyes) were included. All eyes received LSM with erbium: yttrium-aluminum-garnet laser. Spherical equivalent, true accommodation, pseudo-accommodation, wavefront aberrations, and extended range of focus (EROF), or collectively known as DROF, were evaluated using a ray tracing aberrometer. True accommodation referred to the difference in spherical equivalent between distance and near vision, whereas EROF (sum of true and pseudo-accommodation) was determined by measuring the difference in diopters (D) between near and distance through-focus curves, at 50% threshold of the visual Strehl ratio of optical transfer function., Results: From before to seven months after surgery, there was a significant increase in true accommodation from 0.6 ± 1.0 D before surgery to 5.9 ± 2.8 D at seven months after surgery (P < 0.001). EROF increased significantly from 3.4 ± 1.0 D before surgery to 11.1 ± 4.6 D at seven months after surgery (P < 0.001). Ocular aberrations did not vary significantly between preoperative and various postoperative timepoints in either disaccommodated or accommodated states (P > 0.05). No adverse event such as scleral perforation or hypotony was noted., Conclusions: This non-human primate study demonstrated that LSM serves as a novel therapy for improving accommodation and DROF function biomechanically, with a positive response observed throughout the seven-month postoperative period., Translational Relevance: This proof-of-concept study highlights the potential of LSM as a novel treatment for vision recovery in presbyopic eyes.

Thyroid hormones are key regulators of development and metabolism in vertebrates. During the nestling period, young of altricial species transition from an ectothermic phenotype to an endothermic phenotype. Red-winged blackbirds are an altricial species that exhibit an increase in plasma 3,3', 5-triiodo-L-thyronine (T 3 ) levels during the first 5 days post-hatch (dph), begin to develop endothermic metabolic responses by 7 dph, and fledge within 10 days of hatching. We propose that thyroid hormones play an important role in regulating development of endothermy during the nestling period in altricial birds. To better understand the effects of thyroid hormones on endothermic metabolic development in an altricial species, we treated nestling red-winged blackbirds on 2, 3, and 5 dph with either methimazole (MMI) to induce hypothyroidism or supplemental T 3 to induce hyperthyroidism. We then measured on 5, 7, and 9 dph morphology and whole animal O 2 consumption ( V ˙ o 2 ) and ventilation in the thermal neutral zone and during gradual cooling. Treatment of nestlings with MMI resulted in lower plasma T 3 levels on 5 dph that recovered by 7 dph, while supplementing with T 3 did not affect plasma T 3 levels on 5, 7 and 9 dph. Treatment with MMI resulted in smaller nestlings with smaller hearts and structural characters such as wing chord and femur length, but larger lungs and kidneys. Treatment with T 3 produced smaller nestlings with smaller body masses and shorter femur and tarsus lengths. The development of V ˙ o 2 and ventilation endothermic responses to gradual cooling in MMI treated nestlings were delayed when compared with control nestlings. In 9 dph nestlings, hypothyroidism resulted in alterations in the responses of ventilation frequency and tidal volume to cooling when compared with the control nestlings. Supplemental T 3 had no effect on the development of V ˙ o 2 and ventilation in the thermal neutral zone or in response to cooling. Our data suggest plasma thyroid hormone levels play an active role in the systemic development of endothermic capacity and the development of ventilatory control. In the nestling avian, multiple systems develop in concert to produce an endothermic phenotype, but reduced thyroid hormone delays maturation of endothermic capacity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sirsat, Sirsat, Price, Pineda and Dzialowski.)

Migratory birds undergo seasonal changes to muscle biochemistry. Nonetheless, it is unclear to what extent these changes are attributable to the exercise of flight itself versus endogenous changes. Using starlings (Sturnus vulgaris) flying in a wind tunnel, we tested the effects of exercise training, a single bout of flight and dietary lipid composition on pectoralis muscle oxidative enzymes and lipid transporters. Starlings were either unexercised or trained over 2 weeks to fly in a wind tunnel and sampled either immediately following a long flight at the end of this training or after 2 days recovery from this flight. Additionally, they were divided into dietary groups that differed in dietary fatty acid composition (high polyunsaturates versus high monounsaturates) and amount of dietary antioxidant. Trained starlings had elevated (19%) carnitine palmitoyl transferase and elevated (11%) hydroxyacyl-CoA dehydrogenase in pectoralis muscle compared with unexercised controls, but training alone had little effect on lipid transporters. Immediately following a long wind-tunnel flight, starling pectoralis had upregulated lipid transporter mRNA (heart-type fatty acid binding protein, H-FABP, 4.7-fold; fatty acid translocase, 1.9-fold; plasma membrane fatty acid binding protein, 1.6-fold), and upregulated H-FABP protein (68%). Dietary fatty acid composition and the amount of dietary antioxidants had no effect on muscle catabolic enzymes or lipid transporter expression. Our results demonstrate that birds undergo rapid upregulation of catabolic capacity that largely becomes available during flight itself, with minor effects due to training. These effects likely combine with endogenous seasonal changes to create the migratory phenotype observed in the wild., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast cancer receiving neoadjuvant immunotherapy. A total of 249 patients were randomized to standard neoadjuvant chemotherapy with pembrolizumab (pembro) or without pembrolizumab (control). DCE-MRI and DWI, performed prior to and 3 weeks after the start of treatment, were analyzed. Percent changes of tumor ADC metrics (mean, 5th to 95th percentiles of ADC histogram) and FTV were evaluated for the prediction of pathologic complete response (pCR) using a logistic regression model. The area under the ROC curve (AUC) estimated for the percent change in mean ADC was higher in the pembro cohort (0.73, 95% confidence interval [CI]: 0.52 to 0.93) than in the control cohort (0.63, 95% CI: 0.43 to 0.83). In the control cohort, the percent change of the 95th percentile ADC achieved the highest AUC, 0.69 (95% CI: 0.52 to 0.85). In the pembro cohort, the percent change of the 25th percentile ADC achieved the highest AUC, 0.75 (95% CI: 0.55 to 0.95). AUCs estimated for percent change of FTV were 0.61 (95% CI: 0.39 to 0.83) and 0.66 (95% CI: 0.47 to 0.85) for the pembro and control cohorts, respectively. Tumor ADC may perform better than FTV to predict pCR at an early treatment time-point during neoadjuvant immunotherapy.

Background: Despite a publicly funded system, health care in Canada has been shown to be deeply inequitable, particularly toward Indigenous people. Based on research identifying key dimensions of equity-oriented health care as being cultural safety, harm reduction and trauma- and violence-informed care, an intervention to promote equity at the organizational level was tested in primary health care, refined and adapted, and tested in Emergency Departments (EDs)., Methods: In partnership with clinical, community and Indigenous leaders in three diverse EDs in one Canadian province, we supported direct care staff to tailor and implement the intervention. Intervention activities varied in type and intensity at each site. Survey data were collected pre- and post-intervention from every consecutive patient over age 18 presenting to the EDs (n = 4771) with 3315 completing post-visit questions in 4 waves at two sites and 3 waves (due to pandemic constraints) at the third. Administrative data were collected for 12 months pre- and 12 months post-intervention., Results: Throughout the study period, the participating EDs were dealing with a worsening epidemic of overdoses and deaths related to a toxic drug supply, and the COVID 19 pandemic curtailed both intervention activities and data collection. Despite these constraints, staff at two of the EDs mounted equity-oriented intervention strategies; the other site was experiencing continued, significant staff shortages and leadership changeover. Longitudinal analysis using multiple regression showed non-significant but encouraging trends in patient perceptions of quality of care and patient experiences of discrimination in the ED. Subgroup analysis showed that specific groups of patients experienced care in significantly different ways at each site. An interrupted time series of administrative data showed no significant change in staff sick time, but showed a significant decrease in the percentage of patients who left without care being completed at the site with the most robust intervention activities., Conclusions: The trends in patient perceptions and the significant decrease in the percentage of patients who left without care being completed suggest potential for impact. Realization of this potential will depend on readiness, commitment and resources at the organizational and systems levels., Trial Registration: Clinical Trials.gov #NCT03369678 (registration date November 18, 2017)., (© 2022. The Author(s).)

This study evaluated the inter-reader agreement of tumor apparent diffusion coefficient (ADC) measurements performed on breast diffusion-weighted imaging (DWI) for assessing treatment response in a multi-center clinical trial of neoadjuvant chemotherapy (NAC) for breast cancer. DWIs from 103 breast cancer patients (mean age: 46 ± 11 years) acquired at baseline and after 3 weeks of treatment were evaluated independently by two readers. Three types of tumor regions of interests (ROIs) were delineated: multiple-slice restricted, single-slice restricted and single-slice tumor ROIs. Compared to tumor ROIs, restricted ROIs were limited to low ADC areas of enhancing tumor only. We found excellent agreement (intraclass correlation coefficient [ICC] ranged from 0.94 to 0.98) for mean ADC. Higher ICCs were observed in multiple-slice restricted ROIs (range: 0.97 to 0.98) than in other two ROI types (both in the range of 0.94 to 0.98). Among the three ROI types, the highest area under the receiver operating characteristic curves (AUCs) were observed for mean ADC of multiple-slice restricted ROIs (0.65, 95% confidence interval [CI]: 0.52-0.79 and 0.67, 95% CI: 0.53-0.81 for Reader 1 and Reader 2, respectively). In conclusion, mean ADC values of multiple-slice restricted ROI showed excellent agreement and similar predictive performance for pathologic complete response between the two readers.

Crude oil is known to induce developmental defects in teleost fish exposed during early life stages (ELSs). While most studies in recent years have focused on cardiac endpoints, evidence from whole-animal transcriptomic analyses and studies with individual polycyclic aromatic hydrocarbons (PAHs) indicate that the developing kidney (i.e., pronephros) is also at risk. Considering the role of the pronephros in osmoregulation, and the common observance of edema in oil-exposed ELS fish, surprisingly little is known regarding the effects of oil exposure on pronephros development and function. Using zebrafish (Danio rerio) ELSs, we assessed the transcriptional and morphological responses to two dilutions of high-energy water accommodated fractions (HEWAF) of oil from the Deepwater Horizon oil spill using a combination of qPCR and whole-mount in situ hybridization (WM-ISH) of candidate genes involved in pronephros development and function, and immunohistochemistry (WM-IHC). To assess potential functional impacts on the pronephros, three 24 h osmotic challenges (2 hypo-osmotic, 1 near iso-osmotic) were implemented at two developmental time points (48 and 96 h post fertilization; hpf) following exposure to HEWAF. Changes in transcript expression level and location specific to different regions of the pronephros were observed by qPCR and WM-ISH. Further, pronephros morphology was altered in crude oil exposed larvae, characterized by failed glomerulus and neck segment formation, and straightening of the pronephric tubules. The osmotic challenges at 96 hpf greatly exacerbated edema in both HEWAF-exposed groups regardless of osmolarity. By contrast, larvae at 48 hpf exhibited no edema prior to the osmotic challenge, but previous HEWAF exposure elicited a concentration-response increase in edema at hypo-osmotic conditions that appeared to have been largely alleviated under near iso-osmotic conditions. In summary, ELS HEWAF exposure impaired proper pronephros development in zebrafish, which coupled with cardiotoxic effects, most likely reduced or inhibited pronephros fluid clearance capacity and increased edema formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

BACKGROUND. There is a paucity of data and consensus guidelines on the utility of preoperative MRI for planned bilateral prophylactic mastectomy. OBJECTIVE. The purpose of this study was to evaluate the utility of breast MRI performed in high-risk patients for the indication of planned bilateral prophylactic mastectomy, with attention given to the diagnostic performance for breast cancer detection. A secondary aim was to assess the potential impact of breast MRI findings on the decision to perform sentinel lymph node biopsy at the time of prophylactic mastectomy. METHODS. A retrospective database review identified MRI examinations performed at an academic medical center from August 2003 to January 2020 for the indication of planned bilateral prophylactic mastectomy. Patient demographics, imaging findings, operative details, and pathology were recorded. BI-RADS category 1 and 2 assessments were considered negative examinations, and BI-RADS category 3, 4, and 5 assessments were considered positive examinations. Descriptive statistics and performance metrics were calculated. RESULTS. The final cohort included 53 patients (mean age, 45 years). Most (35/53; 66.0%) studies were baseline examinations. Of the 53 patients, 31 (58.5%) had negative MRI examinations and 22 (41.5%) had positive MRI examinations. MRI detected two malignancies (one invasive lobular carcinoma and one high-grade ductal carcinoma in situ), both of which were assessed as BI-RADS category 4. The patient with invasive lobular cancer underwent sentinel lymph node biopsy at the time of mastectomy, which showed metastasis. Breast MRI had sensitivity of 100.0% and specificity of 60.8% for overall breast cancer detection and sensitivity of 100.0% and specificity of 59.6% for invasive cancer detection. CONCLUSION. Preoperative MRI for planned bilateral prophylactic mastectomy detected all cancers, indicating a potential role for MRI in impacting surgical decision making. CLINICAL IMPACT. Given the high NPV for cancer, our results suggest that lymph node biopsy may be safely avoided in patients with a negative MRI examination. This is clinically relevant because sentinel nodes cannot be identified after mastectomy.

Crude oil has multiple toxic effects in fish, particularly during their early life stages. Recent transcriptomics studies have highlighted a potential effect on cholesterol homeostasis and biosynthesis, but have not investigated effects on steroid hormones, which are biosynthetically downstream metabolites of cholesterol. We exposed zebrafish (Danio rerio) embryos and larvae to 3 concentrations of a high energy water accommodated fraction (HEWAF) of crude oil and measured effects on cholesterol and steroid hormones at 48 and 96 h post fertilization (hpf). HEWAF exposure caused a small decrease in cholesterol at 96 hpf but not 48 hpf. HEWAF-exposed larvae had higher levels of androstenedione, testosterone, estradiol, cortisol, corticosterone, and progesterone at 96 hpf compared to controls, while effects at 48 hpf were more modest or not present. 2-Methoxyestradiol was lower following HEWAF exposure at both time points. Dihydrotestosterone was elevated in one HEWAF concentration at 48 hpf only. Our results suggest that hormone imbalance may be an important toxic effect of oil HEWAF exposure despite no major effect on their biosynthetic precursor cholesterol., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: There are currently various conflicting recommendations for breast cancer screening with mammography in women between ages 40-49. There are no specific guidelines for breast cancer screening in women of this age group prior to assisted reproductive technology (ART) for the treatment of infertility. The purpose of our study was to evaluate outcomes of screening mammography, specifically ordered for the purpose of pre-fertility treatment clearance in women aged 40-49 years old., Materials and Methods: This was an IRB approved retrospective study of women aged 40-49 presenting for screening mammography prior to ART between January 2010 and October 2018. Clinical history, imaging, and pathology results were gathered from the electronic medical record. Descriptive statistics were performed., Results: Our study cohort consisted of 118 women with a mean age of 42 years (range 40-49). Sixteen of 118 (14%) women were recalled from screening for additional diagnostic work-up. Five of the 16 (31%) were recommended for biopsy (BI-RADS 4 or 5). One of 5 biopsies yielded a malignant result (PPV 20%). Overall cancer detection rate was 0.85% or 8.5 women per 1000 women screened. The single cancer in this cohort was an ER+ PR+ HER2- invasive ductal carcinoma., Conclusion: Screening mammography in women 40-49 performed prior to initiation of ART may identify asymptomatic breast malignancy. In accordance with ACR and SBI guidelines to screen women of this age group, women of this age group should undergo screening mammography prior to ART., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Objective: The objective of our study was to determine whether, in the digital era, imaging features of a primary breast tumor can be used to influence the decision to biopsy ipsilateral breast calcifications that occur following surgery in women treated with breast conservation surgery (BCS)., Materials and Methods: We retrospectively identified women treated with BCS who subsequently developed suspicious calcifications in the treated breast (BI-RADS 4 or 5) from January 2012 - December 2018. Only cases with histopathological diagnosis by stereotactic or surgical biopsy were included. Pathology reports were reviewed, and biopsy results were considered malignant if invasive carcinoma or ductal carcinoma in situ (DCIS) was found. All other results were considered benign. Fisher's exact test was done comparing frequencies of malignancy between those patients whose original tumor had calcifications versus those whose original tumors were not calcified., Results: Of 90 women with suspicious calcifications on a post-BCS mammogram, 65 (72.2%) were biopsy proven benign and 25 (27.8%) were malignant. The original tumor presented without calcifications in 39 patients (43%), and 51 (57%) had calcifications with or without associated mass, focal asymmetry, or architectural distortion. New calcifications were less likely to be malignant if the original tumor presented without calcifications (5/39; 12.8%) as compared to original tumors with calcifications (20/51; 38.5%) [p-value < 0.05]., Conclusion: New calcifications after BCS are significantly less likely to be malignant if the original tumor presented without calcifications. However, with a PPV of 12.8%, even calcifications in a patient with a non-calcified primary tumor require biopsy., (Copyright © 2021. Published by Elsevier Inc.)

Localization of metastatic axillary lymph nodes in breast cancer patients is an increasingly common procedure performed by radiologists. In 2014, the National Comprehensive Cancer Network guidelines stated that "clinically positive axillary lymph node (s) should be sampled by FNA or core biopsy and clipped with image-detectable marker; clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy". Since then, multiple studies have further supported targeted axillary surgery after neoadjuvant chemotherapy (NAC), with excision of the clipped metastatic axillary node in addition to the sentinel node (s). Requests for image guided localization of clipped axillary nodes will continue to increase and likely become the standard of care. However, when lymph nodes have decreased in size after NAC, or when small deep lymph nodes are sampled, the clipped node can be difficult to identify under ultrasound at the time of localization. When the target node is questionable, we have found it valuable to place an intermediary clip, and use an axillary mammographic view to confirm this intermediary clip co-localizes with the intended target. With this confirmation, safe, accurate localization can then be performed. We describe 3 cases of intermediary clip placement facilitating successful localization of previously clipped axillary lymph nodes., (Copyright © 2020. Published by Elsevier Inc.)

OBJECTIVE. The purpose of this article was to determine the frequency and outcomes of new suspicious findings on breast MRI after initiation of neoadjuvant therapy. MATERIALS AND METHODS. A retrospective database review identified all breast MRI examinations performed to assess response to neoadjuvant therapy between 2010 and 2018. Cases with new suspicious lesions assessed as BI-RADS 4 or 5 and found after the initiation of neoadjuvant treatment were included. Cases with no pretreatment MRI, cases in which the suspicious lesion was present on the baseline MRI but remained suspicious, and cases with insufficient follow-up were excluded. Radiologic, pathologic, and surgical reports were reviewed. Malignant outcomes were determined by pathologic examination. Benignity was established by pathologic examination, follow-up imaging, or both. A total of 419 breast MRI examinations in 297 women were performed to assess response to neoadjuvant therapy. After exclusions, 23 MRI examinations (5.5%) with new suspicious findings, all assessed as BI-RADS 4, comprised the final cohort. RESULTS. Of the 23 lesions, 13 new suspicious findings (56.5%) were contralateral to the known malignancy, nine (39.1%) were ipsilateral, and one (4.3%) involved the bilateral breasts. Lesion types included mass (16, 69.6%), nonmass enhancement (5, 21.7%) and focus (2, 8.7%). None of the new suspicious findings were malignant. CONCLUSION. New suspicious findings occurred in 5.5% of breast MRI examinations performed to monitor response to neoadjuvant therapy, and none of these new lesions were malignant. Our findings suggest that new lesions that arise in the setting of neoadjuvant therapy are highly unlikely to represent a new site of malignancy, particularly if the index malignancy shows treatment response. Larger studies are needed to confirm whether biopsy may be safely averted in this scenario.

Purpose: To assess the use and outcomes of ultrasound for the evaluation of breast signs and symptoms in pediatric females., Methods: A retrospective database review identified all patients ≤18-years-old who underwent breast ultrasound at an academic institution over a 20-year period. Each symptomatic site was designated a case and analyses were performed on each case. Imaging findings were obtained from the radiology reports. Clinical and pathology data were obtained from the medical records. Descriptive statistics were performed., Results: The final cohort comprised 124 cases in 101 patients. Mean age was 15 years (range 1-18). The most common indication for ultrasound was a palpable lump (71%). Thirty-seven cases (30%) demonstrated no sonographic correlate to the symptom; 36 (29%) had a benign correlate. The most common benign correlates were abscess/phlegmon and cyst. All cases of abscess/phlegmon had infectious symptoms. Fifty-one cases (41%) demonstrated a sonographic mass that was not characteristically benign. Of these indeterminate masses, 27 were recommended for biopsy, 13 for short-interval follow-up, and 6 had no recommendation. Of 27 biopsied masses, 63% were fibroadenomas. No symptoms were due to malignancy. Therefore, the NPV of ultrasound was 100% and the PPV 0%., Conclusion: In this cohort of pediatric and adolescent patients, malignancy was never the cause of breast symptoms. Imaging yielded false positives with a biopsy recommendation in 22% of cases. Ultrasound provided value in evaluating infectious symptoms. Given the extreme rarity of breast cancer in this population, surveillance may be a safe alternative for most indeterminate lesions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In the aquatic environment, ubiquitous natural factors such as ultraviolet light (UV) and dissolved organic carbon (DOC) are likely to influence crude oil toxicity. The present study examined the interactive effects of DOC, UV, and DOC-UV co-exposure on the acute toxicity of Deepwater Horizon crude oil in larval red drum (Sciaenops ocellatus). Although DOC alone did not influence crude oil toxicity, it mildly reduced UV photo-enhanced toxicity. Environ Toxicol Chem 2020;39:2509-2515. © 2020 SETAC., (© 2020 SETAC.)

The failure of the swim bladder to inflate during fish development is a common and sensitive response to exposure to petrochemicals. Here, we review potential mechanisms by which petrochemicals or their toxic components (polycyclic aromatic hydrocarbons; PAHs) may affect swim bladder inflation, particularly during early life stages. Surface films formed by oil can cause a physical barrier to primary inflation by air gulping, and are likely important during oil spills. The act of swimming to the surface for primary inflation can be arduous for some species, and may prevent inflation if this behavior is limited by toxic effects on vision or musculature. Some studies have noted altered gene expression in the swim bladder in response to PAHs, and Cytochrome P450 1A (CYP1A) can be induced in swim bladder or rete mirabile tissue, suggesting that PAHs can have direct effects on swim bladder development. Swim bladder inflation failure can also occur secondarily to the failure of other systems; cardiovascular impairment is the best elucidated of these mechanisms, but other mechanisms might include non-inflation as a sequela of disruption to thyroid signaling or cholesterol metabolism. Failed swim bladder inflation has the potential to lead to chronic sublethal effects that are as yet unstudied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

Objective: To evaluate the MRI artifact rendered by the typical injection of a ferromagnetic tracer now being intermittently used for intraoperative sentinel node (SN) identification at our institution, and to explore its impact on postoperative imaging and management., Methods: This study was Institutional Review Board-approved and granted a waiver of consent. A database search tool was used to identify MRI exams performed on patients who had previously undergone breast-conserving surgery with use of a superparamagnetic iron oxide (SPIO) SN tracer between January 1, 2015, and May 1, 2020. MRI reports, images, and relevant demographic, oncologic, and surgical history were collected. The presence or absence of SPIO residue on breast MRI, as well as its impact on image quality, were extracted from the prospective reports., Results: A total of 21 MRI exams were identified in 16 patients who had undergone breast-conservation therapy for cancer with use of SPIO SN tracer. Mean time from particle injection to baseline postoperative MRI exam was 10.8 months. All reports (21/21) noted evidence of SPIO residue. Of these, 5/21 were assessed as non-diagnostic; the remainder were assessed as limited., Conclusion: Radiologists should be aware of the use of superparamagnetic tracers for SN identification and the impact on the quality of future MRI examinations. Alternative injection approaches are being developed and sequence parameters adjusted to minimize artifact., (© Society of Breast Imaging 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Respiratory quotient (RQ) is commonly used to infer which substrates are oxidized, with glucose yielding RQ = 1 and fat normally thought to yield an average of RQ = 0.71. Because fat depot compositions differ among species, we examined how the various common fatty acids affect RQ. RQs ranged from less than 0.7 (e.g., stearic acid) to greater than 0.76 (e.g., docosahexaenoic acid). Furthermore, we conducted a survey of the fatty acid composition of fuel lipids of several vertebrate taxa to determine how the RQ for lipid oxidation during fasting should vary among species. Our survey indicates that most fasting vertebrates from terrestrial ecosystems oxidizing fat should have RQs equaling approximately 0.71, as normally expected. However, some fasting animals in aquatic or marine systems-particularly fish-should have RQs as high as 0.73 when oxidizing only fat. Selective mobilization of fatty acids increased the lipid RQ, but probably by a negligible amount. We conclude that researchers should take habitat and taxon into account when choosing a value for lipid RQ, and preferably should use fatty acid composition for their study species to determine an appropriate RQ for lipids. In the absence of species-specific fatty acid composition data, we suggest assuming a lipid RQ of 0.725 for cold-water fish., (© 2020 Wiley Periodicals LLC.)

Purpose: To compare the characteristics, outcomes, and performance metrics in women undergoing initial breast MRI screening versus subsequent screening., Methods: A retrospective database search identified screening MRIs performed at an academic practice from 2013 to 2015. MRIs were divided into two groups: (1) initial screens and (2) subsequent screens (interpreted with at least one prior MRI for comparison). Benignity was confirmed with pathology or >1-year follow-up. Malignancy was confirmed by pathology. Performance metrics were calculated. Comparisons were made using Binomial and Fisher's exact tests., Results: We observed a higher rate of abnormal interpretations (52% vs. 19%; p < 0.001) and rate of biopsy (49% vs. 15%; p < 0.001) in the initial versus subsequent screen group. The positive predictive value of biopsy was slightly lower at initial versus subsequent screen (17% vs. 19%, p = 0.99). However, the cancer detection rate was higher at initial than at subsequent screen (85 vs. 29/1000, p = 0.08). Sensitivity was higher at initial (100%) versus subsequent (88%) screen. However, the specificity at initial screen was low (55%) compared to subsequent screen (83%)., Conclusions: The higher rate of abnormal interpretations in the initial versus subsequent screen group in part reflects a prevalence screening. Although we observed more abnormal interpretations in the initial screen, this was likely justified by the significantly higher cancer detection. This evidence may be used to counsel patients and referring providers on the expected higher likelihood of recall from an initial screening MRI balanced with higher detection of malignancies. Findings also highlight the importance of having comparison MRIs to decrease false positives., (Copyright © 2020 Elsevier Inc. All rights reserved.)

OBJECTIVE. The purpose of this study was to assess the performance of diagnostic mammography alone for evaluation of palpable symptoms in women with almost entirely fatty breast composition. MATERIALS AND METHODS. All diagnostic mammograms performed for palpable symptoms in women who had been assigned a breast density of "almost entirely fatty" over an 8-year period (2009-2017) at an academic breast center were retrospectively identified. Each symptomatic breast was considered a separate case and analyses were performed at the case level. Clinical, imaging, and pathologic results were reviewed. Descriptive statistics and 2 × 2 contingency table analyses were performed. RESULTS. The study cohort included 323 cases evaluated with mammography. Of these, 294 (91%) had undergone targeted ultrasound. At mammography, 240 (74%) had no correlate to the palpable lump; 38 (12%), a benign correlate; and 45 (14%), a suspicious correlate. Three cases had incidental suspicious mammographic findings, for a total of 48 positive mammography cases. Twenty-seven (8%) cases were malignant. Mammography alone detected all but one cancer, which was detected by ultrasound. In retrospect, the woman from whom this single false-negative mammogram was obtained did not have almost entirely fatty breast density. Mammography alone yielded a negative predictive value of 99.6%, percentage of diagnostic examinations recommended for biopsy that resulted in a tissue diagnosis of malignancy within 1 year of 54%, sensitivity of 96%, and specificity of 93%. Adjunct ultrasound contributed to 11 false-positives but also identified benign correlates in eight cases with no mammographic finding. CONCLUSION. In patients with almost entirely fatty breast tissue presenting with palpable symptoms, mammography alone had a high sensitivity and specificity. Our results support that mammography alone may be sufficient for evaluation of palpable symptoms in these women as long as density criteria are strictly applied.

Objective: To assess the utilization of patient navigators at breast imaging facilities across the United States., Methods: An online survey was distributed to physician members of the Society of Breast Imaging. Questions encompassed use of patient navigators in breast imaging including: presence and qualifications, roles in patient care, perceived benefits, and barriers. Data were analyzed to identify the overall prevalence of patient navigators, their responsibilities and qualifications, and the impact on breast imaging centers., Results: Three-hundred and eighty-five board-certified radiologists practicing in the United States completed the survey. The most common practice types were private practice (52%; 201/385) and academic (29%; 110/385). The majority (67%; 256/385) employed navigators, and the most common qualification was a registered nurse (78%; 200/256). Navigators were used for a variety of patient communication and care coordination roles, most commonly to provide educational resources (86%; 219/256), assist patients with scheduling appointments (80%; 205/256), explain the biopsy process (76%;195/256), and communicate biopsy results (64%). Nearly all (99%; 254/256) respondents ranked patient navigators as valuable to extremely valuable in improving patient care and indicated they would recommend implementation of a patient navigation program to other breast imaging practices. The most common barrier to employing a navigator was the financial cost., Conclusion: Patient navigators have been widely adopted in breast imaging practices across the United States, with two-thirds of respondents reporting use of a navigator. Although navigator roles varied by practice, nearly all radiologists utilizing patient navigators found that they positively impact patient care and would recommend them to other breast imaging practices., (© Society of Breast Imaging 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: There are currently no evidence-based guidelines regarding breast cancer screening in women under 40 prior to initiating assisted reproductive technology (ART). The prevalence of abnormal findings on screening mammography in this population is unknown. The purpose of this study was to describe screening mammography outcomes in women less than 40 years old, referred for the indication of pre-ART., Materials, Methods, Procedures: This is a retrospective review of women less than 40 years old presenting for screening mammography prior to ART between January 2010 and March 2017. Clinical history, breast cancer risk factors, imaging and pathology results were gathered from the electronic medical record., Results: The study included 80 women. Mean patient age was 37 years (range 34-39 years). Sixty-seven (84%) had negative or benign screening (BI-RADS 1 or 2) and 13 (16%) were recalled for diagnostic imaging (BI-RADS 0). Four of 13 (31%) recalled women were given BI-RADS 1 or 2 at diagnostic work-up, 4 (31%) were given a BI-RADS 3, and 5 (38%) were recommended for biopsy (BI-RADS 4). At patient request, 2 of 4 (50%) BI-RADS 3 cases underwent biopsy, for 7 total biopsies. Six (86%) biopsies yielded benign results and 1 (14%) yielded DCIS. Overall cancer yield was 1.3%., Conclusion: In women under 40 who plan to undergo ART, screening mammography may identify breast malignancies. This may be of particular importance given many breast cancers are hormone sensitive, and thus fertility treatments may affect tumor growth. Future, larger studies are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Social inequities are widening globally, contributing to growing health and health care inequities. Health inequities are unjust differences in health and well-being between and within groups of people caused by socially structured, and thus avoidable, marginalizing conditions such as poverty and systemic racism. In Canada, such conditions disproportionately affect Indigenous persons, racialized newcomers, those with mental health and substance use issues, and those experiencing interpersonal violence. Despite calls to enhance equity in health care to contribute to improving population health, few studies examine how to achieve equity at the point of care, and the impacts of doing so. Many people facing marginalizing conditions experience inadequate and inequitable treatment in emergency departments (EDs), which makes people less likely to access care, paradoxically resulting in reliance on EDs through delays to care and repeat visits, interfering with effective care delivery and increasing human and financial costs. EDs are key settings with potential for mitigating the impacts of structural conditions and barriers to care linked to health inequities., Methods: EQUIP is an organizational intervention to promote equity. Building on promising research in primary health care, we are adapting EQUIP to emergency departments, and testing its impact at three geographically and demographically diverse EDs in one Canadian province. A mixed methods multisite design will examine changes in key outcomes including: a) a longitudinal analysis of change over time based on structured assessments of patients and staff, b) an interrupted time series design of administrative data (i.e., staff sick leave, patients who leave without care being completed), c) a process evaluation to assess how the intervention was implemented and the contextual features of the environment and process that are influential for successful implementation, and d) a cost-benefit analysis., Discussion: This project will generate both process- and outcome-based evidence to improve the provision of equity-oriented health care in emergency departments, particularly targeting groups known to be at greatest risk for experiencing the negative impacts of health and health care inequities. The main deliverable is a health equity-enhancing framework, including implementable, measurable interventions, tested, refined and relevant to diverse EDs., Trial Registration: Clinical Trials.gov # NCT03369678 (registration date November 18, 2017).

OBJECTIVE. The objective of this study was to evaluate the feasibility of using a magnetic seed system for preoperative localization of axillary lymph nodes in patients with breast cancer. MATERIALS AND METHODS. We performed a retrospective analysis that included patients with breast cancer who underwent preoperative magnetic seed localization of axillary lymph nodes at our institution between January 1, 2017, and January 1, 2019. Magseed (Endomag) is a nonradioactive inducible magnetic seed that is induced to become a magnet when under the influence of its detector in the operating room. Clinical history, prior axillary sampling and clip placement, and procedure details and surgical outcomes were determined from a search of our PACS and electronic medical records. RESULTS. Thirty-five patients (34 women and one man) composed our study cohort. The mean patient age was 56 years (range, 32-78 years). One patient underwent two separate consecutive localizations for two separate operations, and another patient had bilateral lesions, for a total of 37 axillary lymph node localizations. One case of seed misplacement occurred during the ultrasound-guided localization procedure, resulting in immediate placement of a second seed, for a total of 38 Magseeds placed. All seeds were placed under ultrasound guidance. The mean number of days from seed placement to surgery was 5 days (range, 0-31 days). Thirty-seven of 38 Magseeds (97%) were documented to be successfully retrieved in the operating room. CONCLUSION. Magseed localization appears to be a safe, nonradioactive way to accurately localize axillary lymph nodes preoperatively.

Flying mammals present unique intestinal adaptations, such as lower intestinal surface area than nonflying mammals, and they compensate for this with higher paracellular absorption of glucose. There is no consensus about the mechanistic bases for this physiological phenomenon. The surface area of the small intestine is a key determinant of the absorptive capacity by both the transcellular and the paracellular pathways; thus, information about intestinal surface area and micro-anatomical structure can help explain differences among species in absorptive capacity. In order to elucidate a possible mechanism for the high paracellular nutrient absorption in bats, we performed a comparative analysis of intestinal villi architecture and enterocyte size and number in microchiropterans and rodents. We collected data from intestines of six bat species and five rodent species using hematoxylin and eosin staining and histological measurements. For the analysis we added measurements from published studies employing similar methodology, making in total a comparison of nine species each of rodents and bats. Bats presented shorter intestines than rodents. After correction for body size differences, bats had ~41% less nominal surface area (NSA) than rodents. Villous enhancement of surface area (SEF) was ~64% greater in bats than in rodents, mainly because of longer villi and a greater density of villi in bat intestines. Both taxa exhibited similar enterocyte diameter. Bats exceeded rodents by ~103% in enterocyte density per cm 2 NSA, but they do not significantly differ in total number of enterocytes per whole animal. In addition, there is a correlation between SEF and clearance per cm 2 NSA of L-arabinose, a nonactively transported paracellular probe. We infer that an increased enterocyte density per cm 2 NSA corresponds to increased density of tight junctions per cm 2 NSA, which provides a partial mechanistic explanation for understanding the high paracellular absorption observed in bats compared to nonflying mammals., (© 2019 Wiley Periodicals, Inc.)

The internesting interval separates successive clutches of sea turtle eggs, and its duration varies both among and within species. Here, we review the potential physiological limits to this interval, and develop the hypothesis that desalination capacity limits the internesting interval owing to the requirement for water deposition in eggs. Sea turtles deposit 1-4 kg of water per clutch in egg albumen; for most species, this represents about 2% of adult body mass. We calculate how quickly turtles can recover this water by estimating maximal salt excretion rates, metabolic water production and urinary losses. From this water balance perspective, the 'water-limitation' hypothesis is plausible for green turtles but not for leatherbacks. Some plasma biochemistry studies indicate dehydration in sea turtles during the nesting season, although this is not a universal finding and these data have rarely been collected during the internesting interval itself. There is mixed support for a trade-off between clutch size and the length of the interval. We conclude that the 'water-limitation' hypothesis is plausible for most sea turtle species, but requires direct experimentation.

Sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) is a transmembrane pump critical to muscle calcium cycling during contraction, and SERCA has also been proposed as the basis for a non-shivering thermogenesis mechanism in birds. Despite its potential importance to both shivering and non-shivering thermogenesis, the activity of this transporter has rarely been studied in altricial birds, and never during the developmental transition from ectothermy to endothermy. Here, we describe SERCA activity in the pectoralis muscle and heart ventricle of red-winged blackbird ( Agelaius phoeniceus ) nestlings, fledglings and adults. Additionally, using a diet manipulation, we tested the hypothesis that muscle SERCA activity is affected by dietary fatty acid composition, as has been shown in some previous studies. In blackbird hearts, SERCA activity increased throughout development and into adulthood, conspicuously jumping higher just prior to fledging. In pectoralis muscle, SERCA activity increased throughout the nestling period, but then declined after fledging, an effect we attribute to remodeling of the muscle from a primarily heat-generating organ to a primarily force-generating organ. SERCA activity of the pectoralis muscle was correlated with the proportion of linoleic acid in muscle phospholipids when including all ages in the control group. However, in diet-manipulated birds, there was no consistent relationship between SERCA activity and muscle membrane fatty acid composition at any tested age (5-9 days old). It is unclear whether SERCA might be affected by developmental changes in fatty acid composition at younger ages., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Objective: Treatment of ductal carcinoma in situ (DCIS) is controversial given the variable recurrence and progression to invasive carcinoma. Identifying women who would benefit from adjuvant radiation therapy on the basis of their recurrence risk may allow more individualized management strategies. The Oncotype DX Breast DCIS Score-which we refer to here as the "DCIS score"-is a validated surrogate marker of local recurrence. This study evaluated the association between BI-RADS mammographic calcification descriptors and the DCIS score., Materials and Methods: Fifty-eight women diagnosed with DCIS presenting with calcifications who had Oncotype DX Breast DCIS assay results were identified. Pretreatment BI-RADS mammographic calcification features were collected including morphology, distribution, and maximum span. The association between calcification descriptors and DCIS score was assessed with logistic regression modeling. Mean DCIS scores were calculated for calcification features significantly associated with DCIS score. All analyses were adjusted for patient age, DCIS grade, and progesterone receptor status., Results: Of the suspicious calcifications that proved to represent DCIS, 19.0% were amorphous; 25.9%, coarse heterogeneous; 39.7%, fine pleomorphic; and 15.5%, fine linear or fine linear branching in morphology. The mean DCIS scores by calcification morphology were 22.3, 35.5, 36.7, and 44.1, respectively. Amorphous calcification morphology had a significantly lower adjusted mean DCIS score compared with fine pleomorphic morphology (p = 0.01) and fine linear or fine linear branching morphology (p = 0.02). The adjusted odds ratio (OR) of intermediate or high risk of recurrence (defined as a DCIS score ≥ 39) was significantly higher for women with fine pleomorphic calcifications (OR = 53.1, p = 0.01) and for those with fine linear or fine linear branching calcifications (OR = 24.0, p = 0.04) than for women with amorphous calcifications., Conclusion: Women with amorphous calcification morphology had the lowest DCIS scores compared with women with fine pleomorphic and fine linear or fine linear branching morphologies. Both fine pleomorphic and fine linear or fine linear branching morphologies were associated with higher odds of intermediate or high risk of recurrence. These findings suggest mammographic features are potential biomarkers of DCIS recurrence and could help individualize treatment decisions.

Objective: To determine whether including Indigenous Elders as part of routine primary care improves depressive symptoms and suicidal ideation in Indigenous patients., Design: Prospective cohort study with quantitative measures at baseline and 1, 3, and 6 months postintervention, along with emergency department (ED) utilization rates before and after the intervention., Setting: Western Canadian inner-city primary care clinic., Participants: A total of 45 people who were older than age 18, who self-identified as Indigenous, and who had no previous visits with the clinic-based Indigenous Elders program., Intervention: Participants met with an Indigenous Elder as part of individual or group cultural sessions over the 6-month study period., Main Outcome Measures: Changes in depressive symptoms, measured with the PHQ-9 (Patient Health Questionnaire), following Indigenous patients' encounters with Indigenous Elders. Secondary outcomes included changes in suicide risk (measured with the SBQ-R [Suicidal Behaviors Questionnaire-Revised]) and ED use., Results: Characteristics among those who consented to participate were as follows: 71% were female; mean age was 49 years; 31% had attended residential or Indian day school; and 64% had direct experience in the foster care system. At baseline 28 participants had moderate to severe depressive symptoms (PHQ-9 score of ≥ 10). There was a 5-point decrease that was sustained over a 6-month period ( P = .001). Fourteen participants had an above-average suicide risk score at baseline (SBQ-R score of ≥ 7), and there was a 2-point decrease in suicide risk that was sustained over a 6-month period ( P = .005). For all participants there was a 56% reduction in mental health-related ED visits (80 vs 35) when comparing the 12 months before and after enrolment., Conclusion: Encounters with Indigenous Elders, as part of routine primary care, were associated with a clinically and statistically significant reduction in depressive symptoms and suicide risk among Indigenous patients. Emergency department use decreased, which might reduce crisis-oriented mental health care costs. Further expansion and evaluation of the role of Indigenous Elders as part of routine primary care is warranted., (Copyright© the College of Family Physicians of Canada.)

Rationale: Trade in rhinoceros horn is regulated or banned internationally in recognition of its impact on wild populations worldwide. Enforcement of the laws and regulations depends on successfully identifying when violations occur, which is complicated by the presence of alternative/imitation rhinoceros horn keratin (e.g., bovid horn keratin). In this study, we assess the potential for Direct Analysis in Real Time (DART) ionization paired with Time-Of-Flight Mass Spectrometry (DART-TOFMS) to classify different keratin types from four taxonomic groups: rhinoceros, bovid, domestic horse, and pangolin., Methods: The spectra of 156 keratin samples from all five rhinoceros species (horn keratin), eight genera of bovids (horn keratin), domestic horses (hoof keratin), and all extant species of pangolins (scale keratin) were collected. Fisher ratio analysis identified the most important ions that characterized each class and these ions were used for the training model, which consisted of 143 spectra. Kernel Discriminant Analysis (KDA) was used to classify the different groups., Results: The spectra collected for each taxonomic group are distinctive. The chemotypes demonstrate that the spectra of rhinoceros, bovids, and domestic horse are similar to each other, whereas the chemotypes of pangolins show a different chemical profile. The model built by KDA resolved each taxonomic group: 95% of samples were correctly assigned using leave-one-out cross validation. The 13 blind samples not used in model development were all correctly classified to taxonomic source., Conclusions: DART-TOFMS appears to be a reliable approach for taxonomic identification of keratin. This analysis can be carried out with a small sliver of keratin, with minimal sample preparation, inexpensively and quickly, making it a potential valuable tool for identification of rhinoceros horn and other keratin types., (Published 2018. This article is a US Government work and is in the public domain in the USA.)

Radiomics is an emerging technology for imaging biomarker discovery and disease-specific personalized treatment management. This paper aims to determine the benefit of using multi-modality radiomics data from PET and MR images in the characterization breast cancer phenotype and prognosis. Eighty-four features were extracted from PET and MR images of 113 breast cancer patients. Unsupervised clustering based on PET and MRI radiomic features created three subgroups. These derived subgroups were statistically significantly associated with tumor grade ( p  = 2.0 × 10 -6 ), tumor overall stage ( p  = 0.037), breast cancer subtypes ( p  = 0.0085), and disease recurrence status ( p  = 0.0053). The PET-derived first-order statistics and gray level co-occurrence matrix (GLCM) textural features were discriminative of breast cancer tumor grade, which was confirmed by the results of L2-regularization logistic regression (with repeated nested cross-validation) with an estimated area under the receiver operating characteristic curve (AUC) of 0.76 (95% confidence interval (CI) = [0.62, 0.83]). The results of ElasticNet logistic regression indicated that PET and MR radiomics distinguished recurrence-free survival, with a mean AUC of 0.75 (95% CI = [0.62, 0.88]) and 0.68 (95% CI = [0.58, 0.81]) for 1 and 2 years, respectively. The MRI-derived GLCM inverse difference moment normalized (IDMN) and the PET-derived GLCM cluster prominence were among the key features in the predictive models for recurrence-free survival. In conclusion, radiomic features from PET and MR images could be helpful in deciphering breast cancer phenotypes and may have potential as imaging biomarkers for prediction of breast cancer recurrence-free survival., Competing Interests: The authors declare no competing interests.

Docosahexaenoic acid (DHA) is an important and abundant fatty acid moiety in vertebrate brains. We measured brain phospholipid composition during development in red-winged blackbirds ( Agelaius phoeniceus ), an altricial species that breeds in aquatic habitats. We also manipulated diet by feeding nestlings fish oil or sunflower oil. Finally, we assessed selective uptake of yolk by comparing the yolk fatty acid composition of freshly laid eggs and day-old hatchlings. Relative to other altricial species, blackbirds achieved high DHA in brain phospholipids (20% of phospholipid fatty acids in day-old hatchlings). This was not a result of selective uptake from the yolk, but rather a consequence of a high proportion of DHA in the yolk (2.5% of total lipids) at laying. Our dietary study confirmed that nestling brains are sensitive to fatty acid supply. Red-winged blackbirds may be able to advance cognitive development relative to other altricial species owing to their aquatic maternal diet., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Endothermy is a conspicuous and important adaptation in birds. Even though juvenile and adult birds are endothermic and maintain a constant, high body temperature by means of internal heat production, they begin life expressing an ectothermic phenotype. Depending on where a species falls along a continuum of maturity at hatching, from precocial to altricial, they begin to express endothermic traits either close to the time of hatching or as nestlings over a period of 1-3 weeks. Developing endothermy requires attaining a high basal metabolic rate and associated aerobic scope to produce sufficient internal heat, insulation to retain the internally produced heat, and a thermostat that "turns on" heat production in response to cooling ambient temperatures. To support the high metabolic costs of endothermy, the animal must have the capacity to deliver sufficient oxygen and nutrients to the heat-generating tissues. In this review, we examine the development of physiological and morphological traits that are required for endothermy and discuss their potential to limit the development of endothermy. These include ventilatory and cardiovascular function, contribution of visceral organ masses, membrane lipid composition, substrate supply pathways, and skeletal muscle physiology. The developmental trajectories of each of these systems in precocial and altricial species can have significant effects on the development of an endothermic phenotype.