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Background: MetaMap is a valuable tool for processing biomedical texts to identify concepts. Although MetaMap is highly configurative, configuration decisions are not straightforward.Objective: To develop a systematic, data-driven methodology for configuring MetaMap for optimal performance.Methods: MetaMap, the word2vec model, and the phrase model were used to build a pipeline. For unsupervised training, the phrase and word2vec models used abstracts related to clinical decision support as input. During testing, MetaMap was configured with the default option, one behavior option, and two behavior options. For each configuration, cosine and soft cosine similarity scores between identified entities and gold-standard terms were computed for 40 annotated abstracts (422 sentences). The similarity scores were used to calculate and compare the overall percentages of exact matches, similar matches, and missing gold-standard terms among the abstracts for each configuration. The results were manually spot-checked. The precision, recall, and F-measure (β =1) were calculated.Results: The percentages of exact matches and missing gold-standard terms were 0.6–0.79 and 0.09–0.3 for one behavior option, and 0.56–0.8 and 0.09–0.3 for two behavior options, respectively. The percentages of exact matches and missing terms for soft cosine similarity scores exceeded those for cosine similarity scores. The average precision, recall, and F-measure were 0.59, 0.82, and 0.68 for exact matches, and 1.00, 0.53, and 0.69 for missing terms, respectively.Conclusion: We demonstrated a systematic approach that provides objective and accurate evidence guiding MetaMap configurations for optimizing performance. Combining objective evidence and the current practice of using principles, experience, and intuitions outperforms a single strategy in MetaMap configurations. Our methodology, reference codes, measurements, results, and workflow are valuable references for optimizing and configuring MetaMap.

Interoperable clinical decision support system (CDSS) rules are a pathway to achieving interoperability which is a well-recognized challenge in health information technology. Building an ontology facilitates the creation of interoperable CDSS rules, which can be achieved by identifying the keyphrases (KP) from the existing literature. However, KP identification for labeling the data requires human expertise, consensus, and contextual understanding. This paper aims to present a semi-supervised framework for the CDSS using minimal labeled data based on hierarchical attention over the documents fused with domain adaptation approaches. Then, evaluate the effectiveness of KP identification with this framework. In the view of semi-supervised learning, our methodology toward building this framework outperforms the prior neural architectures by learning with document-level context, no explicit hand-crafted features, knowledge transfer from pre-trained models (on unlabeled corpus), and post-fine-tuning with smaller gold standard-labeled data. To the best of our knowledge, this is the first functional framework for the CDSS sub-domain to identify the KP, which is trained on limited labeled data. It contributes to the general natural language processing (NLP) architectures in areas such as clinical NLP, where manual data labeling is challenging.

Clinical decision support systems (CDSSs) are important for the quality and safety of healthcare delivery. Although CDSS rules guide CDSS behavior, they are not routinely shared and reused.Ontology has the potential to promote the reuse of CDSS rules. Therefore, we systematically screened literature to elaborate on the current status of ontology applied in CDSS rules, such as rule management (which uses captured CDSS rule usage data and user feedback data to tailor CDSS services to be more accurate) and maintenance (which updates CDSS rules). Through this systematic literature review, we aim to identify the frontiers of ontologies used in CDSS rules.The literature search was focused on the intersection of ontology, clinical decision support, and rules in PubMed, the Association for Computing Machinery (ACM) Digital Library, and the NursingAllied Health Database. Grounded theory and PRISMA 2020 guidelines were followed. One author initiated the screening and literature review, while the other two validated the processes and results independently. Inclusion and exclusion criteria were developed and refined iteratively.CDSSs were primarily used to manage chronic conditions, alerts for medication prescriptions, reminders for immunizations and preventive services, diagnoses, and treatment recommendations among the 81 included publications. The CDSS rules were presented in Semantic Web Rule Language, Jess, or Jena formats. Despite the fact that ontologies have been used to provide medical knowledge, CDSS rules, and terminologies, they have not been used in CDSS rule management or to facilitate the reuse of CDSS rules.Ontologies have been used to organize and represent medical knowledge, controlled vocabularies, and the content of CDSS rules. So far, there has been little reuse of CDSS rules. More work is needed to improve the CDSS rule reusability and interoperability. This paper identified and described the ontologies that, despite their limitations, enable Semantic Web technology and their applications in CDSS rules.

Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent studies suggest that BAs regulate T helper 17 cell function, but the underlying mechanism of this action and their therapeutic value in disease models remains unclear. Using an IL-23 minicircle DNA-based murine model of psoriasiform dermatitis, we showed that oral administration of secondary BAs, including lithocholic acid (LCA), deoxycholic acid, and 3-oxoLCA, significantly improved psoriasiform dermatitis without inducing apparent hepatotoxicity. Of the BAs tested, LCA possessed the greatest potency in treating psoriasiform dermatitis. Intravenous administration of LCA at a much lower dosage (compared with oral treatment) showed a comparable antipsoriatic effect and markedly suppressed the IL-17A response. Exvivo experiments revealed that LCA reduced IL-17A production in IL-23-stimulated murine T cells in the absence of BA receptors TGR5 or FXR. Strikingly, BAs inhibited CCL20 expression in keratinocytes, which led to reduced migration of CCR6-expressing Jurkat cells cultured in the conditioned medium of stimulated keratinocytes. Thus, BAs improve psoriasiform dermatitis with minimal toxicity via direct inhibition of IL-17A production and blockade of CCL20-mediated trafficking, supporting the potential use of BAs in psoriasis.

ObjectiveWe examined the perspectives of the general public on 29 health indicators to provide evidence for further prioritizing the indicators, which were obtained from the literature review. Health status is different from disease status, which can refer to different stages of cancer.DesignThis study uses a cross-sectional design.SettingAn online survey was administered through Ohio University, ResearchMatch, and Clemson University.ParticipantsParticipants included the general public who are 18 years or older. A total of 1153 valid responses were included in the analysis.Primary outcomes measuresParticipants rated the importance of the 29 health indicators. The data were aggregated, cleaned, and analyzed in three ways: (1) to determine the agreement among the three samples on the importance of each indicator (IV = the three samples, DV = individual survey responses); (2) to examine the mean differences between the retained indicators with agreement across the three samples (IV = the identified indicators, DV = individual survey responses); and (3) to rank the groups of indicators after grouping the indicators with no mean differences (IV = the groups of indicators, DV = individual survey responses).ResultsThe descriptive statistics indicate that the top-five rated indicators are drug or substance abuse, smoking or tobacco use, alcohol abuse, major depression, diet and nutrition. The importance of 13 of the 29 health indicators was agreed upon among the three samples. The 13 indicators were categorized into seven groups. Groups 1-3 were rated as significantly higher than Groups 4-7.ConclusionsThis study provides a baseline for prioritizing further the 29 health indicators, which can be used by electronic health records or personal health record system developers. Currently, self-rated health status is used predominantly. Our study provides a foundation to track and measure preventive services more accurately and to develop an individual health status index.Strengths and limitations of this studyThe work establishes the foundation to measure individual health status more comprehensively and objectivelyThe work reflects perspectives from three communities with a relatively large sample sizeThe work provides the foundation to prioritize the 29 health indicators furtherWith real-world longitudinal data, the public perspective data on individual health status measurement would be verified and validated further

Background The Lapidus procedure has become a popular procedure in correcting hallux valgus deformities and has undergone several modifications in an effort to improve the efficacy of the procedure. The senior author modifies this procedure with the addition of an intermetatarsal and intercuneiform fusion. Our hypothesis is that this will improve the procedure outcomes and decrease deformity recurrence. Methods We reviewed patient charts who underwent the procedure between 2014 and 2017 performed by the senior author. This yielded 47 reviewable cases, with 34 meeting study criteria. The cases were analyzed for standard hallux valgus measurements (intermetatarsal angle [IMA], hallux valgus angle [HVA]) and fusion on X-ray. Results The results of the study showed partial intermetatarsal and intercuneiform fusion failure in seven (20%) cases, and one case where the great toe fell into varus. These cases were excluded. In the remaining cases, there was a statistically significant improvement in the HVA and IMA between the preoperative X-ray and first postoperative X-ray. Additionally, there was no significant difference between HVA and IMA between first and final postoperative radiographs. There was a significant increase in IMA for the fusion failure cases (p=0.001). Conclusion Clinically, our findings demonstrate that successful union is possible with low recurrence and complication rates when using this modification of the Lapidus procedure in patients with hallux valgus deformity.

We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation. In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17A‒producing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis. Treatment with broad-spectrum antibiotics suppressed IL-23‒mediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intake‒induced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.

OBJECTIVE To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target. METHODS First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade. Healthy tendon stromal cells were stimulated in vitro with IL-1β to assess the production of CCL20 by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of conditioned media from stimulated tenocytes in inducing T cell migration was interrogated using a Transwell system. RESULTS We observed an up-regulation of both CCR6 and CCL20 in the enthesis of IL-23 MC-treated mice, which was confirmed in human biopsy specimens. Specific targeting of the CCR6/CCL20 axis with a CCL20 locked dimer (CCL20LD) blocked entheseal inflammation, leading to profound reductions in clinical and proinflammatory markers in the joints and skin of IL-23 MC-treated mice. The stromal compartment in the tendon was the main source of CCL20 in this model and, accordingly, in vitro activated human tendon cells were able to produce this chemokine and to induce CCR6+ T cell migration, the latter of which could be blocked by CCL20LD. CONCLUSION Our study highlights the pathogenic role of the CCR6/CCL20 axis in enthesitis and introduces the prospect of a novel therapeutic approach for treating patients with PsO and PsA.

Category: Other; Ankle; Ankle Arthritis; Bunion Introduction/Purpose: Foot and ankle surgeries are often be accompanied by a peripheral nerve block as a method of reducing post-operative pain. The major nerve targeted is the popliteal nerve. The nerve can be supplemented with a target of the adductor canal or saphenous nerve. Higher than expected complication rates with peripheral nerve blocks has led to increased concern among both surgeons as well as patients. To our knowledge, no study has been able to identify risk factors that may predispose a patient to one of these complications. Our goal was to attempt to identify those risk factors. Methods: We reviewed patient charts who underwent a foot and ankle procedure between 2014 and 2018 as performed by the senior author. The review yielded 992 procedures performed across four surgical locations. Of these, 137 procedures were removed because no regional block was used. The remaining cases were analyzed for nerve complications, defined as sensory (paresthesia, numbness, tingling, or burning pain) or motor (weakness or paralysis) deficits along the distribution of a peripheral nerve. The patients were divided into blocked patients with and without complications. The groups were evaluated for demographic differences. The categories consisted of age, sex, diabetic status, smoking, previous procedures, previously diagnosed neuropathies, surgical location, body mass index (BMI), race, and insurance provider. Statistical analysis was performed using SAS software. To determine significance of these different factors, Chi-square values were obtained for each data set. Additionally, a regression analysis was performed to identify odds ratio for individual factors. Results: The overall complication rate was 10.1% with a total of 855 blocks given. The significant factors associated with a complication were age (p=0.0061), BMI (p=0.0031), location (p=0.0016), and smoking status (p=0.0026). Factors that were not significantly associated with complications were sex, diabetes status, previous procedures requiring a block, previously diagnosed neuropathies, race, and insurance provider. A regression analysis was performed to determine odds ratio for individual factors. Those with significant higher odds ratio were age between 40-65 years, normal or underweight BMI, surgery occurring at an Outpatient Surgery Center, and current smoker. Conclusion: Current literature has reviewed operative variables such as tourniquet time and epinephrine use, while others have looked at diabetes and age as predictors of nerve block complications. Our study focuses more on epidemiological factors that can predict an increased risk. Our study helped to reinforce the findings previous literature has found in regards to age and diabetes status. This study has also introduced some new factors that can help the surgeon decide if a nerve block is necessary for each surgical patient. [Table: see text]

Introduction Isolated gastrocnemius equinus contracture has been associated with several foot and ankle pathologies within the literature. The Silfverskiold test is commonly used to identify isolated gastrocnemius contracture, however, the proper technique for performing the test has been scrutinized. The purpose of this study was to determine if there is a clinical significance in the ankle dorsiflexion that is obtained when the examination is performed incorrectly with a single hand versus the correct two-hand technique. Methods Thirty consecutive new patients with conditions associated with gastrocnemius equinus were included in the study. The Silfverskiold test was performed with a two-hand technique and a single-hand technique. The amount of dorsiflexion obtained with the knee in full extension was measured and recorded using an extendable goniometer for each technique, with the arms aligned with the fifth metatarsal and fibular head. Results The average amount of dorsiflexion that was obtained with the two-hand technique with the knee in full extension was 76.3°±4.2°. When the one-hand technique was utilized the average amount of dorsiflexion obtained with the knee in full extension was 88.4°±4.2°. This was found to be statistically significant (p

CCR6 is important for the trafficking of IL-17A–producing γδ T cells and required for the development of psoriasiform dermatitis in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23–mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type and CCR6-deficient (CCR6-knockout) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, wild-type mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. CCR6-knockout mice were resistant to IL-23–induced skin inflammation but exhibited no changes in joint inflammation compared with wild-type mice. Depletion of neutrophils protected wild-type mice from skin and joint disease without suppressing T helper type 17 cytokine expression. In contrast, mice lacking γδ T cells showed a partial reduction in neutrophilic recruitment and a significant decrease in IL-17A expression in skin and paw tissue. Thus, in an IL-23–mediated model that allows concurrent assessment of both skin and joint disease, we showed that CCR6 is critical for inflammation in the skin but not in the joint. Furthermore, our data suggest that neutrophils and γδ T cells are key effector cells in IL-23–mediated skin and joint inflammation in mice.

Category: Bunion Introduction/Purpose: The Lapidus procedure is becoming more popular in the surgical correction of hallux valgus deformities. Bunion correction surgeries in general demonstrate good patient outcomes, however the recurrence rates are variable and are a concern for patient morbidity. The senior author of this study performs a modified Lapidus procedure where the first intermetatarsal, and first intercuneiform joints are fused along with the standard fusion of the first tarsometatarsal joint. We believe that this fusion will address the recurrence rate associated with the Lapidus procedure. Our theory is that recurrence occurs at the normally unfused intermetatarsal and intercuneiform joints, and when these joints are fused recurrence will be unable to occur. Methods: We reviewed the charts of patients who underwent the modified Lapidus procedure between 2014 and 2017 performed by the senior author. This review yielded 47 cases, of which 34 met the study criteria as a primary bunion repair with a preoperative X-ray, a postoperative X-ray at first surgical follow up, and a final postoperative X-ray =90 days postoperatively. Of the 13 charts that did not qualify, 11 had inadequate follow up data/radiographs, and 2 cases were revisions. The 34 remaining cases were then analyzed for IMA, HVA, and evidence of fusion on X-ray. Two patient subsets were created for additional analysis of the first and last postoperative X-rays with no patient overlap. 19 cases created subgroup A as they contained patients whose last postoperative X-rays were weight bearing. 6 cases were analyzed as subgroup B having final postoperative X-rays that were non-weight bearing. All first postoperative X-rays were non-weight bearing. Results: The average time of radiographic follow up was 10.5±8.9 months (range 3.1-41.5). There was evidence of fusion failure at the IMT joint in 7 cases (21%), and these patients were removed from group data analysis. Another case was excluded due to the great toe falling into varus. In the remaining 26 cases, the difference in IMA and HVA was significant between the last preoperative and first postoperative X-ray (pConclusion: Our study results suggest that the modified Lapidus procedure has good results in the short term, maintaining the operative reduction at a mean follow up time of 10 months. Our hypothesis that the intermetatarsal and intercuneiform joint fusion prevents bunion recurrence is supported by the fused cases showing no significant differences after at least 90 days postoperatively, while the unfused cases showed significant changes to their IMA angles after at least 90 days postoperatively. Although the study population is small, our data suggests that this procedure can maintain the correction achieved in surgery.

Category: Ankle, Sports Introduction/Purpose: Chronic lateral ankle instability (LAI) is a common cause of ankle pain. Surgical interventions have been shown to be highly effective in alleviating patient’s symptoms once conservative care has failed. Stress radiographs have not demonstrated a clear efficacy in diagnosing ankle instability. Currently, MRI is considered to be superior to stress radiographs in the available literature. Unfortunately, the literature comparing these methods is limited. The purpose of this study is to compare the results of an MRI and manual inversion stress radiographs, in order to assess the accuracy of each modality in assessing the lateral ankle ligament competence. We believe that stress radiographs may have more value in confirming chronic ankle instability than the more expensive MRI imaging. Methods: A retrospective chart review was performed between January 2016 - July 2018 for patients diagnosed with LAI. The review identified 318 cases, of which 57 met the study criteria of having both an AP manual inversion stress radiographs, assessed by the senior author, and MRI, interpreted by a musculoskeletal radiologist, occurring within 6 months of each other without an acute injury within 12 weeks of the first image. For the remaining 57 cases, the imaging was reviewed in the following manner. For the MRI studies, the report was read from the radiologist assessing the lateral ankle complex. A positive MRI was denoted as pathology being reported by the radiologist. For the manual inversion stress radiograph, measurements were made to assess the degree of talar tilt while being stressed. A positive stress radiograph was identified based on asymmetry of the ankle joint during the stress. Results: The average time between imaging studies was 7.2±7.4 weeks (range 0.5-24 weeks). Of the 57 cases that qualified for the study, 43 (75%) had a positive stress radiograph, and 21(37%) had a positive MRI. 24 cases (42%) demonstrated a positive stress radiograph with a negative MRI, while 2 cases (4%) demonstrated a negative stress radiograph with a positive MRI. In respect to talar tilt, those patients identified as having a positive stress radiograph also had a higher average talar tilt when compared to those who did not. The degree of talar tilt for each set of criteria is summarized in Table 1. Conclusion: Historically, lateral ankle instability has been a clinical diagnosis. When further imaging is needed, our data suggests stress radiographs may demonstrate a higher reliability than MRI when assessing the competence of the lateral ankle ligaments. Asymmetry in a joint during an inversion stress examination has been shown to be indicative of multi ligament involvement. Few studies have attempted to define a talar tilt consistent with instability and our data does not meet those numbers. However, with the addition of bundled care and rising health care costs, we believe this provides a potential alternative in confirming a diagnosis of ankle instability.

BackgroundA clinical decision support system (CDSS) covers a broad spectrum of applications, for example, screening reminders, can reduce malpractice, improve preventive services and enable better management of chronic conditions. CDSSs have traditionally been used successfully in large hospitals. The availability (ie, whether the function is provided by the software) and usage (ie, actual use) of a CDSS in office-based primary care settings, however, are less well studied.ObjectiveTo establish a benchmark of CDSS availability and usage in office-based primary care settings, particularly given the large volume of visits in such settings.MethodsWe used the 2015 Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey to conduct secondary data analysis. We selected preventive services reminders and drug interaction alerts, along with several other variables as examples of a CDSS.ResultsCDSS usage rates ranged from 68.5% to 100% among solo or non-solo primary care practices owned by physicians or physician groups that have electronic medical records (EMRs)/electronic health records (EHRs) and 44.7% to 96.1%, regardless of EMR/EHR status. According to proportion tests, solo practices had significantly lower CDSS usage and availability rates on several measures if the practice is entirely EMR/EHR based and significantly lower (16.3%–28.9%) CDSS usage rates than did non-solo practices on each measure, regardless of EMR/EHR status.ConclusionIn the USA, a CDSS, especially under the categories of basic preventive reminders and drug interaction alerts, is used routinely between 68% and 100% in primary care if a practice is entirely EMR/EHR based. More work is needed, however, to determine the reasons for large usage gaps between solo and non-solo practices and to reduce such gaps.

Category: Hindfoot Introduction/Purpose: Plantar fasciitis is a debilitating problem that can cause long-term pain. Multiple different studies with various modalities have been suggested to treat the inflammation of the plantar fascia. None of them have provided a cause for the inflammation. A few recent studies have shown gastrocnemius equinus to be a driving factor in foot pain, which includes plantar fasciitis. Our belief is that the inflammation is due to a stretch placed on the plantar fascia due to a gastrocnemius equinus contracture and the beginning of an arch collapse per the Grand Rapids arch collapse model. As such, we wanted to review our results with an isolated gastrocnemius recession for the treatment of plantar fasciitis. Methods: We retrospectively reviewed patient data collected by isolating ICD-9 and ICD-10 codes for plantar fasciitis. These patients presented to the senior author’s office with a complaint of plantar heel pain, were diagnosed with a gastrocnemius equinus contracture and plantar fasciitis, failed conservative treatment, and opted for an isolated gastrocnemius recession as a definitive treatment of the fasciitis. From the timeframe of 1/1/2015 to 6/12/17, there were 68 out of 97 patients who qualified for the study based on the necessary criteria: an initial consultation pain score, initial post-operative pain score at two weeks, and second post-operative pain score at eight weeks. These patients did not have coexisting surgeries at the time of the gastrocnemius recession or prior surgery to the area in discussion. Results: For the 68 patients (five of which underwent bilateral procedures at a minimum of six weeks apart), who elected to have a gastrocnemius recession for plantar fasciitis, the average initial presenting pain was a 7.4 on a scale of 0 to 10. The average initial post-operative pain score was 2.8 and the average second post-operative pain score was 3.3. The average number of days from initial to second post-operative appointment was 136 days. Of the 68 patients, 21 returned after their eight-week post-operative visit for evaluation. Only 3 returned with recurrent plantar heel pain, 4 more presented with new onset tarsal tunnel syndrome, three more with heel pain different from their pre operative pain and the remaining patients had new onset unrelated pain. Conclusion: We have demonstrated that an isolated gastrocnemius recession can decrease the pain score in patients with recalcitrant plantar fasciitis. Follow up care beyond eight weeks post operation is not routinely performed due to the limited nature of the procedure. The improvement demonstrated in the VAS scores of the patients included in this study show a definite improvement and as such, we believe that an isolated gastrocnemius recession should be considered as a definitive treatment of plantar fasciitis. Future prospective randomized studies will need to be completed to further evaluate the effectiveness of this procedure.

Objectives Adenomyoepithelioma of the breast is an uncommon biphasic breast lesion characterized by a cytologically bland epithelial and myoepithelial proliferation. It is often considered benign and thought to represent a variant of intraductal papilloma. However, rare cases of adenomyoepitheliomas have been reported to show malignant transformation. Features that favor malignancy include increased mitoses, necrosis, atypia, cellular pleomorphism, and infiltrative borders. Most reported cases of malignant adenomyoepithelioma demonstrate carcinomas arising in a benign adenomyoepithelioma. Methods A 74-year-old woman presented to the hospital with an 8-month history of a palpable right breast mass. Mammogram demonstrated an irregular marginated mass, and a needle core biopsy of the mass showed atypical sclerosing adenosis. A lumpectomy revealed a firm, tan-white, ill-defined 2.7-cm mass abutting the anterior and posterior margins. Results Histologic examination showed an infiltrative proliferation of epithelial-lined tubules surrounded by myoepithelial cells with clear cytoplasm. There were focal areas of hypercellularity with marked cytologic atypia in both the epithelial and myoepithelial components. Focal necrosis and increased mitoses (12/10 HPF) were also identified. On immunohistochemical studies, the epithelial cells were positive for CK7 while the myoepithelial cells were highlighted by p63, SMMHC, SMA, and CK5/6. Ki-67 showed an increased proliferative index (35%). ER, PR, and HER-2 immunostains were negative. The overall histologic and immunohistochemical findings support a diagnosis of malignant biphasic adenomyoepithelioma. No in situ carcinoma was identified. After the diagnosis was reported, a follow-up reexcision with axillary sentinel lymph node excision was performed. Both specimens were negative for malignancy. Conclusion Malignant adenomyoepithelioma of the breast is an uncommon entity and it is strongly associated with local recurrence and distant metastases. Awareness of its distinctive histologic and immunohistochemical features will be helpful in initiating the appropriate medical management for patients with this entity, which is crucial for improving prognosis and overall survival.

Given a set $S$ of $n$ points in the unit square $[0,1]^d$, an optimal traveling salesman tour of $S$ is a tour of $S$ that is of minimum length. A worst-case point set for the traveling salesman problem in the unit square is a point set $S^{(n)}$ whose optimal traveling salesman tour achieves the maximum possible length among all point sets $S\subset [0,1]^d$, where $|S|=n$. An open problem is to determine the structure of $S^{(n)}$. We show that for any rectangular parallelepiped $R$ contained in $[0,1]^d$, the number of points in $S^{(n)}\cap R$ is asymptotic to $n$ times the volume of $R$. Analogous results are proved for the minimum spanning tree, minimum-weight matching, and rectilinear Steiner minimum tree. These equidistribution theorems are the first results concerning the structure of worst-case point sets like $S^{(n)}$.

It is proved that there are constants $c_1$, $c_2$, and $c_3$ such that for any set $S$ of $n$ points in the unit square and for any minimum-length tour $T$ of $S$ (1) the sum of squares of the edge lengths of $T$ is bounded by $c_1 \log n$; (2) the number of edges having length $t$ or greater in $T$ is at most $c_2/t^2$; and (3) the sum of edge lengths of any subset $E$ of $T$ is bounded by $c_3 |E|^{1/2}$. The second and third bounds are independent of the number of points in $S$, as well as their locations. Extensions to dimensions $d>2$ are also sketched. The presence of the logarithmic term in (1) is engaging because such a term is not needed in the case of the minimum spanning tree and several analogous problems, and, furthermore, we know that there always exists some tour of $S$ (which perhaps does not have minimal length) for which the sum of squared edges is bounded independently of $n$.

It is proved that the length of the longest possible minimum rectilinear Steiner tree ofn points in the unitd-cube is asymptotic tosdn(d?1)/d, wheresd is a constant that depends on the dimensiond?2. A method of Chung and Graham (1981) is generalized to dimensiond to show that 1≤sd≤d4(1?d)/d. In addition to replicating Chung and Graham's exact determination ofs2=1, this generalization yields new bounds such as 1≤s3

We prove that, in all dimensions, the total weight of a worst-case minimal rectilinear Steiner tree in the unit d-cube is at least n(d−1) d .

It is proved that there are constants c1, c2, and c3 such that for any set S of n points in the unit square and for any minimum-lengths of T of S (1) the sum of squares of the edge lengths of T is bounded by c1 log n, (2) the sum of edge lengths of any subset E of T is bounded by c2|E|1/2, and (3) the number of edges having length t or greater in T is at most c3/t2. The second and third bounds are independent of the number of points in S, as well as their locations. Extensions to dimensions d>2 are also sketched.The presence of the logarithmic term in (1) is engaging because such a term is not needed in the case of the minimum spanning tree and several analogous problems, and, furthermore, we know that there always exists some tour of S (which perhaps does not have minimal length) for which the sum of squared edges is bounded independently of n.

Features related to the perimeter of the convex hull C n of a random walk in R 2 are studied, with particular attention given to its length L n . Bounds on the variance of L n are obtained to show that, for walks with drift, L n obeys a strong law. Exponential bounds on the tail probabilities of L n under special conditions are also obtained. We then develop simple expressions for the expected values of other features of C n , including the number of faces, the sum of the lengths and squared lengths of the faces, and the number of faces of length t or less

A method is presented for determining the asymptotic worst-case behavior of quantities like the length of the minimal spanning tree or the length of an optimal traveling salesman tour of n points in the unit d-cube. In each of these classical problems, the worst-case lengths are proved to have the exact asymptotic growth rate of $\beta _n^{{{(d - 1)} / d}} $, where $\beta $ is a positive constant depending on the problem and the dimension. These results complement known results on the growth rates for the analogous quantities under probabilistic assumptions on the points, but the results given here are free of any probabilistic hypotheses.