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Background: Despite advances in breast cancer imaging, research and treatment, higher mortality among racial/ethnic minority and low-income populations persists. Consent and enrollment of diverse and vulnerable patients into breast cancer research is critical. Given this urgent need for diversity in breast cancer research, successful collection and banking of fresh biospecimens from diverse patients is key to ameliorating some of the cancer disparities. Given our access to a unique and vulnerable patient population, we developed and implemented a clinical information and biospecimen repository for patients evaluated in the breast radiology and breast oncology outpatient clinics at Boston Medical Center (BMC). Our goal was to consent patients for donation of percutaneous breast biopsy samples, surgical tissue, and blood to develop a breast cancer biospecimen bank. Our long-term goal is to provide high-yield human samples for translational research studies in breast cancer from a diverse and vulnerable patient population. Methods: We designed a multi-disciplinary team of clinical providers and basic science researchers to envision a breast cancer biospecimen bank for research. Key stakeholders were identified, workflow was arranged, IRB obtained, and research staff trained. Patients presenting with suspicious mass on breast imaging (BI-RADS 4C and 5 categories) were eligible to enroll. Two percutaneous biopsy cores were obtained for research at the time of ultrasound guided biopsy. We leveraged the Hematology Oncology translational research program at Boston Medical Center and pilot finding to launch the project. Results: Since initiation in April 2021, we approached 68 patients and consented 44, for a successful consent rate of 64.7%. Of the 44 patients consented, 22 (50.0%) identified themselves as Black/African American, 11 (25.0%) as White/Caucasian, 10 (22.73%) as Hispanic and 1 (2.27%) as Asian. Of all patients enrolled, 41 (93.2%) had a breast malignancy, of which 27 (70.7%) were hormone-sensitive and 7 (17.1%) were TNBC. Additionally, of the 44 patients on study, only 9 (20.4%) had commercial insurance or managed care plan on the day of the consent. In total, 84 percutaneous biopsy cores were collected from 42 patients. Corresponding surgical tissue, plasma, serum and PBMCs were also obtained. Conclusion: Our program demonstrates that the enrollment of diverse and vulnerable breast cancer patients onto cancer research is achievable. We successfully created a breast biopsy program to provide access to diverse human samples for breast cancer translational research studies. Currently this repository serves to address many ongoing translational projects to understand: 1) the gap in knowledge of inherent differences in tumor biology and tumor environment, 2) metabolic regulation in the breast cancer microenvironment, and 3) heterogeneity of tumors and its effects on clinical outcomes and microenvironment interactions. Citation Format: Adrian Ilinski, Kiana Mahdaviani, Michael Fishman, Michael Cassidy, Naomi Ko. Prospective breast biopsy collection at an urban safety-net hospital serving a diverse patient population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-01.

Background: Spinal cord stimulation (SCS) is a highly effective therapy for treating and management of refractory chronic pain. However, complex nature of pain and infrequent in-clinic visits, determining subject’s long-term response to the therapy remains difficult. Frequent measurement of pain in this population can help with early diagnosis, disease progression monitoring, and evaluating long-term therapeutic efficacy. This paper compares the utilization of the common subjective patient-reported outcomes with objective measures captured through a wearable device for predicting the response to SCS therapy. Method: Data is from the ongoing international prospective post-market REALITY clinical study, which collects long-term patient-reported outcomes from 557 subjects and the sub-study designed for collecting additional wearables data on a subset of participants for up to six months after SCS implantation. We first implemented a combination of dimensionality reduction algorithms and correlation analyses to explore the mathematical relationships between objective wearable data and subjective patient-reported outcomes. We then developed machine learning models to predict SCS therapy outcome based on the subject’s response to NRS or PGIC. Results: Principal component analysis results showed that psychological aspects of pain were closely associated with heart rate variability, while movement-related measures were closely associated with patient-reported outcomes related to physical function and social role participation. Our machine learning models using objective wearable data predicted both PGIC and NRS outcomes with high accuracy in the absence of subjective data. The prediction accuracy was higher for PGIC compared with the NRS using subjective-only measures primarily driven by the patient satisfaction feature. Similarly, the PGIC questions, reflects an overall change since the study onset and could be a better predictor of long-term therapy outcome. Conclusions: The significance of this study is to introduce a novel use of wearable data collected from a subset of patients to capture multi-dimensional aspects of pain and compare the prediction power with the subjective data from a larger data set. The discovery of pain digital biomarkers could result in a better understanding of the patient’s response to therapy and their general well-being.

Spinal Cord Stimulation (SCS) is a well-established therapy for treating chronic pain. However, treatment response to SCS therapy may vary among people with chronic pain due to diverse pain perspectives amongst them. While, currently, chronic pain is evaluated by clinically validated patient reported outcomes (PROs) measures completed during a clinical assessment, monitoring improvement of the participant’s progress over time and comparison of PROs across participants remains subjective and challenging. Thus, objective measures to quantify pain are invaluable. This study aims to assess the feasibility of using digital biomarkers collected from wearables during SCS treatment to predict pain and PRO outcomes. Twenty participants with chronic pain were recruited and implanted with SCS. During the six months of the study, activity and physiological metrics were collected and data from 15 participants was used to develop a machine learning pipeline to objectively predict pain and PRO measures. We were able to reach the accuracy of 0.832 ± 0.012 in pain intensity prediction. The feature importance analysis showed that digital biomarker from the smart watch such as heart rate, heart rate variability, step count, and stand time can contribute to modeling different aspects of pain. The results of the study suggest that wearable biomarkers can be used to predict therapy outcomes in people with chronic pain and bring us another step closer towards objective evaluation of chronic pain.

Multidisciplinary patient-reported outcomes are a critical part of assessing patients to better understand their well-being during treatment. The use of multidisciplinary patient-reported outcomes is recommended in many areas of medicine. The Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) has been utilized as a common measurement language across universally relevant domains, including pain, mood, sleep, social participation, and function.Retrospective analysis of prospectively collected data was performed. Subjects were identified and consecutively enrolled upon entry into chronic pain centers across 24 sites in the United States. The PROMIS-29 v2.1 and the numerical rating scale (NRS) were recorded. The pain impact score and the Health Utilities Index Mark 3 (HUI-3) were calculated. Statistical differences were assessed between genders and among age groups comprising subjects less than 40, 41-60, 61-80, and over 80 years of age.A total of 19,546 patients were assessed over the enrollment period from 2018 to 2020. The PROMIS-29 v2.1 was evaluated across the seven domains, along with the numerical rating sale (NRS). The mean scores of the population for PROMIS SF v1.0 Pain Interference 4a, PROMIS SF v1.0 Sleep Disturbance 4a, PROMIS SF v1.0 Fatigue 4a, PROMIS SF v1.0 Anxiety 4a, PROMIS SF V1.0 Depression 4a, PROMIS SF v2.0 Ability to Participate in Social Roles and Activities 4a, and PROMIS SF v1.0 Physical Function 4a, measuring pain interference, sleep disturbance, fatigue, anxiety, depression, social participation, and physical function, were 64.61, 57.19, 58.50, 53.94, 54.45, 40.06, and 36.23, respectively. Pain intensity was 6.38 on an 11-point NRS scale. The pain impact score (PIS) and health utilities index mark 3 (HUI-3) scores, calculated across the designated age groups, were 33.19 and 0.67, respectively. Statistical differences were observed for the domains of sleep disturbance and physical function for age groups less than 40 and greater than 80 years of age.This data set is the first published normative data set describing the PROMIS-29 assessment in the chronic pain population. The patient population is more homogeneous than expected, and females were found to have higher levels of dysfunction.

This book offers a new way to conceptualize and study differences among democracies, focusing on political conduct and interaction as well as related taken-for-granted assumptions. With an empirical basis in a multimethod study of Portugal and Spain, pioneers in the worldwide turn to democracy that began in the 1970s, the argument identifies how political inclusion and equality vary substantially as a result of processes that the book theorizes: Nationally predominant forms of democratic practice constitute cultural legacies of the countries’ pathways to democracy during the 1970s. Whereas Portugal moved from dictatorship to democracy through a social revolution that inverted hierarchies and reconfigured cultural patterns while also generating thorough political democratization, Spain experienced a regime-led process of political transition under pressure from the opposition. The book shows how this contrast in pathways put in place ways of understanding democracy that have had deep consequences for political inclusion and conduct. Points of contrast in contemporary democratic practice include patterns of interaction between social movement protest and elected power holders as well as conduct within representative entities and in crucial secondary institutions such as the news media and the educational system. Consequences are identified in distributional outcomes, housing and welfare state policies, employment policy, and in the handling of economic crises. The implications of Spain’s less inclusionary democratic practice for cultural “others” such as Catalans are taken up in the chapter on the Catalan crisis. Implications for democratic theory and for sociological and political science theory are also taken up.

It remains unknown whether and how sports medicine physicians currently utilize genetic testing in their clinical practice. This study sought to assess knowledge of, experience with, and attitudes towards genetic testing by sports medicine physicians in the United States (US). An email with a survey hyperlink was distributed twice to members of the American Medical Society for Sports Medicine (AMSSM) listserv in September 2016, with approximately a 10% response rate. Questions focused on knowledge of, experience with, and attitudes towards testing for different genes related to sports proficiency, injury risk, and disease risk. Few AMSSM physicians believe that genetic testing to adapt training (12%) or to choose a sport (2%) is ready for clinical adoption. Most respondents self-reported minimal knowledge about, and limited experience with, genetic testing. The main exception was screening for sickle cell trait (SCT) for which most (84%) reported moderate/significant/expert knowledge and over two-thirds had ordered testing. Although most respondents thought it appropriate to counsel and test for health conditions associated with cardiac and connective tissue disorders in the setting of a positive family history, only a minority had been asked to do so. Five or fewer respondents (2%) had been asked to test for performance-associated variants (Angiotensin Converting Enzyme (ACE) II and Alpha-Actinin 3 (ACTN3)), and five or fewer (2%) would recommend changes based on the results. Our study provides a baseline of current US sports medicine physicians&rsquo, minimal experiences with, and knowledge of, genetic testing. The findings of our study indicate that sports medicine physicians require further genetics education as it relates to sports and exercise in order to be prepared to competently engage with their patients and to develop sound professional organizational policies.

Background Every year, millions of children in the United States participate in youth full-contact sports, which carry concussion risks—the long-term sequelae of which are not well understood. We examined the attitudes and knowledge of adults in Chicago about youth sports participation, concussion risk, and whether physicians should counsel against youth participation in full-contact sports. Methods An anonymous paper survey featuring 13 attitudinal, 13 demographic, and 9 knowledge questions was distributed to a convenience sample of adults ≥18 years in hospital waiting areas and four Chicago parks. Participants were asked to hypothetically consider themselves the parent of a 10-year-old child regarding attitudes towards full-contact sports participation. Results Between June 13 and July 27, 2016, 1091 partial or complete valid surveys were collected. Almost half (46%) of respondents would not allow a hypothetical 10-year-old son to play tackle football. The majority (74%) of respondents agreed that it was appropriate for physicians to counsel against youth participation in full-contact sports. Respondents obtained information about concussions from, on average, 2–3 sources, although only 34% received information from physicians. Respondents demonstrated a high concussion knowledge level (average: 6.75 of 9 questions). However, only 39% of respondents correctly answered that the following statement was false: “After a mild concussion, there are usually visible changes on medical imaging”. Conclusions Overall, respondents are well-informed about concussions. They are divided about the participation of youth in full-contact sports and are amenable to physician counseling against youth participation in full-contact sports.

Objectives: To examine the gender of authors of original research in 3 high-impact pediatric journals between 2001 and 2016, given the importance of publishing on academic promotion, and to compare authorship gender with the percentage of women on editorial boards and with academic faculty composition. Study design: We assessed the prevalence of female first and senior (last-listed) authorship of original research articles published in 3 pediatric-focused journals Pediatrics, JAMA Pediatrics (entitled Archives of Pediatric and Adolescent Medicine until 2013), and The Journal of Pediatrics. We also examined the gender breakdown of the main editors and the broader editorial boards of these journals. In addition, we examined whether junior female faculty co-authored with male or female senior faculty. Results: Of 3895 original articles, 22 were excluded because the gender of either the first or senior author could not be determined from the name. An analysis of authorship by year showed increasing female representation across the selected journals in both first (39.8% in 2001, 57.7% in 2016) and senior (28.6% in 2001, 38.1% in 2016) authors, respectively. Editorial boards also showed increasing female representation (17.8% in 2001 to 39.8% in 2016). Junior female faculty were more likely to co-author with senior female women (female first and last author); the gap remained unchanged despite the increasing number of women entering pediatrics. Conclusions: Women are underrepresented as authors and editors, although the gap is closing. Junior women are less likely to co-author with senior men, which may be a disservice given current gender disparities in promotion and leadership.

Objective To examine attitudes and practices of pediatricians toward sports-related head trauma and youth participation in tackle football and ice hockey. Study design A respondent-anonymous electronic survey was distributed 3 times to members of the American Academy of Pediatrics Section of Bioethics, Council on Injury, Violence, and Poison Prevention, and Council on Sports Medicine and Fitness. Results Of 791 eligible pediatricians, 227 (29%) responded. Most respondents (189/223; 85%) treat sports-related concussions, among whom 83% (137/165) reported access to an established return-to-play protocol within their practice. Virtually all (160/166; 96%) reported increased parental awareness/concern regarding concussions and 85% (139/163) reported increased visits for head trauma. Overall, 77% (140/183) would not allow their son to play tackle football and 35% (64/181) and 34% (63/184) would not allow their son or daughter, respectively, to participate in ice hockey. Most respondents endorsed limiting or eliminating tackling (143/176; 81%) and checking (144/179; 80%) from practice. Respondents were evenly divided in their support for counseling against youth participation in full-contact sports, with 48% in favor (87/180). Conclusions Most respondents would not allow their own child to play tackle football and endorsed limiting or eliminating tackling in practice. The American Academy of Pediatrics should consider recommending restrictions on tackling in football to support the current concussion concerns of its members.

Nitric oxide (NO) and its metabolites are implicated in carcinogenesis and metastasis. Both stimulatory and inhibitory effects of NO have been reported in relation to breast cancer and its role in the development of malignancies and metastasis remains uncertain. We have used the polyomavirus middle T antigen (PyV-mT) targeted to the mouse mammary gland and bred into an inducible NO synthase (iNOS)deficient C57Bl/6 strain to examine a role for nitric oxide in modulating tumors that develop in the complex environment of the whole animal. The development of hyperplasias was delayed to the extent that the earliest palpable tumors arose 2– 4 weeks later in PyV-mT/iNOS / mice compared with PyV-mT/iNOS / mice, identifying a role for iNOS in early events in mammary tumor formation. Tumors that did develop in PyV-mT/iNOS / mice were characteristically well differentiated and had a cribriform pattern. Other tumors were myoepithelial adenocarcinomas with uniform nuclear size. In contrast, mice capable of iNOS activity typically developed solid nodular adenocarcinomas with a high mitotic index and pleomorphic nuclei. No significant effect of iNOS deficiency was found on vascular density in hyperplasias or tumors by examining CD31-positive vessels. The infiltration of lesions by macrophages, cells capable of significant NO production, remained unchanged in PyV-mT/iNOS / mice. Metastatic potential was retained by PyV-mT-transformed epithelium in the absence of iNOS, indicating that NO production by iNOS is not essential for this process. These results indicate a role for iNOS in tumorigenesis, particularly in the regulation of early events. © 2003 Wiley-Liss, Inc.

all projects are funded. In the region of multiplicity, the move from a pooling (socially efficient) equilibrium to a valuation (socially inefficient) equilibrium involves many features of a financial crisis: prices decline (interest spreads rise); real investment declines; unsophisticated investors leave the market (flight to quality) and sophisticated investors make profits; trust declines and due diligence increases.

An epidural abscess developed several weeks after a traumatic esophageal rupture secondary to a reported flexion-extension injury in a restrained back seat passenger in a motor vehicle accident. Chest radiograph and an Indium study suggested the possibility of a posterior mediastinal abscess. Chest computed tomography (CT) also noted epidural abscess and osteomyelitis, which were confirmed by magnetic resonance imaging (MRI). Diagnosis was delayed significantly by underinterpretation of both chest and CT findings. Obvious positive findings (lower lobe infiltrate on chest radiograph and posterior mediastinal abscess on CT) were noted, but more subtle and very important findings of superior mediastinal widening and extra pulmonary gas bubbles on the chest radiograph and extradural disease displacing the spinal cord on CT were not described. We can find no previously reported case of esophageal rupture associated with flexion-extension injury of the neck. It is also extremely rare for esophageal rupture to remain asymptomatic for more than several hours.

The federal government delegates various aspects of financial market regulation to self-regulatory organizations (SROs) such as the New York Stock Exchange and the National Association of Securities Dealers. We model one regulatory task of an SRO, the enforcement of rules designed to prevent the SRO's members from cheating customers. Specifically, we focus on the determination of an SRO's optimal policy for investigating agents who may have defrauded customers and the penalties associated with fraud. We model contracting/enforcement as a two-tier problem. First, an SRO chooses its enforcement policy, consisting of a specification of the likelihood that an agent is investigated for fraud and a penalty schedule. We assume that the SRO's objective is to maximize the welfare of its members, the agents. Taking the SRO's enforcement policy as given, agents compete with one another to handle customer transactions. They compete by offering contracts promising (outcome-contingent) payoffs that maximize customers' expected utility. When choosing an enforcement policy, the SRO anticipates the competition among its members. Indeed, we show that the SRO's optimal enforcement policy is designed to mute this competition. In doing so, an SRO chooses a more lax enforcement policy than would be preferred by customers. Investigations for cheating are less frequent and penalties are lower than what a customer would choose. Moreover, a decrease in investigation cost might lead an SRO to actually investigate less. Enforcement will become more vigorous, however, as a customer's alternatives to dealing with an agent of the SRO improve. A general conclusion of the analysis is that control of the enforcement policy governing contracts confers substantial market power to a group of otherwise competitive agents. In fact, we show that if agents are risk neutral, control of the enforcement policy is equivalent to agents behaving as monopolists. We also investigate the effect of government oversight on the self-regulatory process. We show that in equilibrium the threat of governmental enforcement will lead to more rigorous enforcement by the SRO, to the benefit of customers. Moreover, this benefit is achieved even without actual governmental enforcement taking place.