Physician engagement in reproductive health advocacy: findings from a mixed methods evaluation of a leadership and advocacy program.

BACKGROUND: Medical curricula include advocacy competencies, but how much physicians engage in advocacy and what enables this engagement is not well characterized. The authors assessed facilitators and barriers to advocacy identified by physician alumni of a reproductive health advocacy training program. METHODS: The authors present secondary results from a mixed methods program evaluation from 2018 to 2020, using alumni data from a cross-sectional survey (n = 231) and in-depth interviews (IDIs, n = 36). The survey measured engagement in policy, media, professional organization, and medical education advocacy and the value placed on the community fostered by the program (eight questions, Cronbach's alpha = 0.81). The authors estimated the association of community value score with advocacy engagement using multivariable Poisson regression to estimate prevalence ratios and analyzed IDI data inductively. RESULTS: Over one third of alumni were highly engaged in legislative policy (n = 90, 39%), professional organizations (n = 98, 42%), or medical education (n = 89, 39%), with fewer highly active in media-based advocacy (n = 54, 23%) in the year prior to the survey. Survey and IDI data demonstrated that passion, sense of urgency, confidence in skills, and the program's emphasis on different forms of advocacy facilitated engagement in advocacy, while insufficient time, safety concerns, and sense of effort redundancies were barriers. The program community was also an important facilitator, especially for "out loud" efforts and for those working in environments perceived as hostile to abortion care (e.g., alumni in hostile environments with high community value scores were 1.8 times [95% CI 1.3, 2.6] as likely to report medium/high levels of media advocacy compared to those with low scores after adjusting for age, gender, and clinical specialty). CONCLUSION: Physician advocacy training curricula should include both skills- and community-building and identify a full range of forms of advocacy. Community-building is especially important for physician advocacy for reproductive health services such as abortion care.

Approaches to Research Ethics in Health Research on YouTube: Systematic Review.

BACKGROUND: YouTube has become a popular source of health care information, reaching an estimated 81% of adults in 2021; approximately 35% of adults in the United States have used the internet to self-diagnose a condition. Public health researchers are therefore incorporating YouTube data into their research, but guidelines for best practices around research ethics using social media data, such as YouTube, are unclear. OBJECTIVE: This study aims to describe approaches to research ethics for public health research implemented using YouTube data. METHODS: We implemented a systematic review of articles found in PubMed, SocINDEX, Web of Science, and PsycINFO following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. To be eligible to be included, studies needed to be published in peer-reviewed journals in English between January 1, 2006, and October 31, 2019, and include analyses on publicly available YouTube data on health or public health topics; studies using primary data collection, such as using YouTube for study recruitment, interventions, or dissemination evaluations, were not included. We extracted data on the presence of user identifying information, institutional review board (IRB) review, and informed consent processes, as well as research topic and methodology. RESULTS: This review includes 119 articles from 88 journals. The most common health and public health topics studied were in the categories of chronic diseases (44/119, 37%), mental health and substance use (26/119, 21.8%), and infectious diseases (20/119, 16.8%). The majority (82/119, 68.9%) of articles made no mention of ethical considerations or stated that the study did not meet the definition of human participant research (16/119, 13.4%). Of those that sought IRB review (15/119, 12.6%), 12 out of 15 (80%) were determined to not meet the definition of human participant research and were therefore exempt from IRB review, and 3 out of 15 (20%) received IRB approval. None of the 3 IRB-approved studies contained identifying information; one was explicitly told not to include identifying information by their ethics committee. Only 1 study sought informed consent from YouTube users. Of 119 articles, 33 (27.7%) contained identifying information about content creators or video commenters, one of which attempted to anonymize direct quotes by not including user information. CONCLUSIONS: Given the variation in practice, concrete guidelines on research ethics for social media research are needed, especially around anonymizing and seeking consent when using identifying information. TRIAL REGISTRATION: PROSPERO CRD42020148170; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148170.

Ethical and Methodological Considerations of Twitter Data for Public Health Research: Systematic Review.

BACKGROUND: Much research is being carried out using publicly available Twitter data in the field of public health, but the types of research questions that these data are being used to answer and the extent to which these projects require ethical oversight are not clear. OBJECTIVE: This review describes the current state of public health research using Twitter data in terms of methods and research questions, geographic focus, and ethical considerations including obtaining informed consent from Twitter handlers. METHODS: We implemented a systematic review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, of articles published between January 2006 and October 31, 2019, using Twitter data in secondary analyses for public health research, which were found using standardized search criteria on SocINDEX, PsycINFO, and PubMed. Studies were excluded when using Twitter for primary data collection, such as for study recruitment or as part of a dissemination intervention. RESULTS: We identified 367 articles that met eligibility criteria. Infectious disease (n=80, 22%) and substance use (n=66, 18%) were the most common topics for these studies, and sentiment mining (n=227, 62%), surveillance (n=224, 61%), and thematic exploration (n=217, 59%) were the most common methodologies employed. Approximately one-third of articles had a global or worldwide geographic focus; another one-third focused on the United States. The majority (n=222, 60%) of articles used a native Twitter application programming interface, and a significant amount of the remainder (n=102, 28%) used a third-party application programming interface. Only one-third (n=119, 32%) of studies sought ethical approval from an institutional review board, while 17% of them (n=62) included identifying information on Twitter users or tweets and 36% of them (n=131) attempted to anonymize identifiers. Most studies (n=272, 79%) included a discussion on the validity of the measures and reliability of coding (70% for interreliability of human coding and 70% for computer algorithm checks), but less attention was paid to the sampling frame, and what underlying population the sample represented. CONCLUSIONS: Twitter data may be useful in public health research, given its access to publicly available information. However, studies should exercise greater caution in considering the data sources, accession method, and external validity of the sampling frame. Further, an ethical framework is necessary to help guide future research in this area, especially when individual, identifiable Twitter users and tweets are shared and discussed. TRIAL REGISTRATION: PROSPERO CRD42020148170; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148170.

Sexual and Reproductive Health Advocacy Successes, Failures, and Needs in the United States: Perspectives From Key Stakeholders.

Physician advocates for sexual and reproductive health (SRH) care have been active in the United States for decades. Despite such activism, access to SRH services has been fraught with persistent restrictions, particularly for abortion care. We sought the perspectives of key stakeholders on what makes for an effective SRH physician advocate and thoughts about the successes, failures, and needs of the abortion advocacy movement. We interviewed 15 SRH key informants (KIs) in sectors with expertise in organizational policy and advocacy (n = 6); clinical leadership and education (n = 3), media (n = 3), and reproductive justice (n = 3). The analytic team coded repeating ideas and conducted a thematic analysis, organizing findings within KI perspectives on the role of physician advocates in the field of abortion and contraception; successes, failures, and needs in abortion and contraception advocacy; and recommendations on the composition and components of an ideal clinician advocacy training program. KIs relayed that skill building related to communication, developing relationships with changemakers, and understanding political systems was critical for effective advocacy. They felt clinician advocacy training programs should include providers other than physicians and be designed for trainees to build relationships with one another over time. KI perspectives can be valuable in informing advocacy training programs and for contributing strategic approaches to increasing equitable and widespread access to SRH services.

Use of Comparative Case Study Methodology for US Public Health Policy Analysis: A Review.

CONTEXT: There is growing recognition that policies influence population health, highlighting the need for evidence to inform future policy development and reform. OBJECTIVES: This review describes how comparative case study methodology has been applied to public health policy research and discusses the methodology's potential to contribute to this evidence. METHODS: English-language, peer-reviewed articles published between 1995 and 2012 were sought from 4 databases. Articles were included if they described comparative case studies addressing US public health policy. Two researchers independently assessed the 20 articles meeting review criteria. MAIN OUTCOME MEASURES: Case-related characteristics and research design tactics utilized to minimize threats to reliability and validity, such as the use of multiple sources of evidence and a case study protocol, were extracted from each article. RESULTS: Although comparative case study methodology has been used to analyze a range of public health policies at all stages and levels, articles reported an average use of only 3.65 (out of 10) research design tactics. CONCLUSION: By expanding the use of accepted research design tactics, public health policy researchers can contribute to expanding the evidence needed to advance health-promoting policies.

The use of social media for reproductive health advocacy among physicians: a content analysis of tweets by physicians engaged in reproductive health care.

BACKGROUND: Physician voices on social media are important for health policy advocacy. However, the extent to which physicians use best practices around health communications strategy is unknown. METHODS: We implemented a content analysis of 1373 tweets from 12 physicians who specialize in reproductive health care and participated in a reproductive health-related advocacy training program, to describe their reproductive health advocacy tweets in terms of levels of engagement, tone, framing and target audience. RESULTS: The most common framing centered on identifying abortion and contraception as essential health care services. Approximately one-third used proactive (37%), reactive (33%), and neutral (30%) strategies. Less than one-quarter (19%) of the tweets explicitly self-identified as a physician. CONCLUSIONS: Participants used a range of message frames, tones, and audience engagement tactics, suggesting a deliberate health communications strategy. Advocacy training discusses the importance of these domains when using social media for advocacy.

Bone metastases in germ cell tumours: lessons learnt from a large retrospective study.

OBJECTIVE: To determine the characteristics of patients with germ cell cancer and bone metastases. PATIENTS AND METHODS: The case records of patients with known germ cell tumours (GCTs) within the Anglian Germ Cell Cancer Group database between January 2005 and March 2011 were reviewed retrospectively. Data were collected for histopathology, presence of bone metastases at diagnosis or relapse, site of bone metastases and imaging method used to confirm bone metastases, treatment received, response to treatment and overall survival. We present here the largest unselected cohort of bone metastases in patients with GCTs. RESULTS: In all, 2550 cases of GCTs were reviewed and there was bone involvement in 19 cases. The primary site was either testicular (13/19), mediastinal (1/19) or unknown (5/19). Most cases were non-seminomatous GCTs (11/19, 58%) and only three cases of seminomatous GCTs (3/19, 16%) with five cases in which diagnosis was based on clinical history and significantly raised GCT markers (5/19, 26%). In all of these five cases ß-human chorionic gonadotrophin was raised and in three α-fetoprotein was raised, consistent with non-seminomatous GCT. There were bone metastases at diagnosis (0.51%, 13/2550) or at relapse (0.24%, 6/2550). The sites of bone metastases were the vertebrae (15/19, 79%), pelvis (3/19, 16%), ribs (3/19, 16%) and femur (2/19, 11%). Ten patients (53%) had solitary, and nine patients (47%) had multiple, sites of bone metastases. In patients presenting with bone metastases at diagnosis compared with relapse, the mortality rate was 23% (3/13) and 50% (3/6), respectively. After receiving one line of chemotherapy, nine patients (47%) remained in remission not requiring further treatment, six (32%) required further chemotherapy due to subsequent relapse, three (16%) died after first-line chemotherapy and one was lost to follow-up. At the time of data collection and based on the last clinic follow-up, six patients (32%) had died with a median (interquartile range, IQR) follow-up of 11.5 (4.3, 24.8) months and 10 (53%) remained alive with a median (IQR) follow-up of 26 (13.5, 48) months Three patients were lost to follow-up. Of the known patients alive, eight (42%) remained in remission and two (11%) had recurrent disease requiring further treatment. CONCLUSION: Although bone disease in germ cell cancer is rare, awareness of this condition is important and there is a need for prospective evaluation of patient characteristics, treatment approaches and survival outcome in this group of patients.

Lessons from Hurricane Sandy: a community response in Brooklyn, New York.

The frequency and intensity of extreme weather events have increased in recent decades; one example is Hurricane Sandy. If the frequency and severity continue or increase, adaptation and mitigation efforts are needed to protect vulnerable populations and improve daily life under changed weather conditions. This field report examines the devastation due to Hurricane Sandy experienced in Red Hook, Brooklyn, New York, a neighborhood consisting of geographically isolated low-lying commercial and residential units, with a concentration of low-income housing, and disproportionate rates of poverty and poor health outcomes largely experienced by Black and Latino residents. Multiple sources of data were reviewed, including street canvasses, governmental reports, community flyers, and meeting transcripts, as well as firsthand observations by a local nonprofit Red Hook Initiative (RHI) and community members, and social media accounts of the effects of Sandy and the response to daily needs. These data are considered within existing theory, evidence, and practice on protecting public health during extreme weather events. Firsthand observations show that a community-based organization in Red Hook, RHI, was at the center of the response to disaster relief, despite the lack of staff training in response to events such as Hurricane Sandy. Review of these data underscores that adaptation and response to climate change and likely resultant extreme weather is a dynamic process requiring an official coordinated governmental response along with on-the-ground volunteer community responders.

Physician perspectives of abortion advocacy: findings from a mixed-methods study.

OBJECTIVE: Our aim was to assess physicians' perspectives of what constitutes abortion advocacy and the skills needed to be effective in their efforts to safeguard legal abortion. METHODS: Alumni from a physician training programme for sexual and reproductive health advocacy completed a cross-sectional survey including questions on perceived skills needed for effective advocacy. The research team conducted in-depth interviews (IDIs) with alumni, based on their level of engagement in advocacy. We present descriptive statistics for survey data and themes identified in the interview data using techniques informed by grounded theory. RESULTS: Of the survey respondents (n=231), almost a third (28.6%; n=66) felt the most important media skill they learnt was the ability to stay on message. The most important policy skill was communicating effectively with policymakers (47.0%; n=108), followed by distilling evidence for policymakers and laypeople (13.0%; n=30). In the IDIs (n=36), participants reported activities such as media interviews as clear examples of advocacy, but also considered implementing institutional policies and abortion provision to be advocacy. They discussed how individual comfort and capacity for advocacy activities may change over time, given personal and professional considerations. Regardless of the type of activity, physicians valued strategic communication and relationship-building skills. CONCLUSIONS: Based on our findings, training programmes that seek to mobilise physician advocates to advance sexual and reproductive health and rights should work with trainees to create a tailored advocacy plan that fits their personal and professional lives and goals. Regardless of the types of advocacy activities physicians focus on, strategic communication may be central in skills-based training.

Ethical considerations and methodological uses of Facebook data in public health research: A systematic review.

OBJECTIVE: Since 2016, around seven in 10 adults in the United States (U.S.) actively use Facebook. While much Facebook data is publicly available for research, many users may not understand how their data are being used. We sought to examine to what extent research ethical practices were employed and the research methods being used with Facebook data in public health research. METHODS: We conducted a systematic review (PROSPERO registration CRD42020148170) of social media-based public health research focused on Facebook published in peer-reviewed journals in English between January 1, 2006 and October 31, 2019. We extracted data on ethical practices, methodology, and data analytic approaches. For studies that included verbatim user content, we attempted to locate users/posts within a timed 10-min period. RESULTS: Sixty-one studies met eligibility criteria. Just under half (48%, n = 29) sought IRB approval and six (10%) sought and obtained informed consent from Facebook users. Users' written content appeared in 39 (64%) papers, of which 36 presented verbatim quotes. We were able to locate users/posts within 10 min for half (50%, n = 18) of the 36 studies containing verbatim content. Identifiable posts included content about sensitive health topics. We identified six categories of analytic approaches to using these data: network analysis, utility (i.e., usefulness of Facebook as a tool for surveillance, public health dissemination, or attitudes), associational studies of users' behavior and health outcomes, predictive model development, and two types of content analysis (thematic analysis and sentiment analysis). Associational studies were the most likely to seek IRB review (5/6, 83%), while those of utility (0/4, 0%) and prediction (1/4, 25%) were the least likely to do so. CONCLUSIONS: Stronger guidance on research ethics for using Facebook data, especially the use of personal identifiers, is needed.

Cryotherapy following total knee replacement.

BACKGROUND: Total knee replacement (TKR) is a common intervention for patients with end-stage osteoarthritis of the knee. Post-surgical management may include cryotherapy. However, the effectiveness of cryotherapy is unclear. OBJECTIVES: To evaluate the acute (within 48 hours) application of cryotherapy following TKR on pain, blood loss and function. SEARCH METHODS: We searched the Cochrane Database of Systematic Reviews, CENTRAL, DARE, HTA Database, MEDLINE, EMBASE, CINAHL, PEDro and Web of Science on 15th March 2012. SELECTION CRITERIA: Randomised controlled trials or controlled clinical trials in which the experimental group received any form of cryotherapy, and was compared to any control group following TKR indicated for osteoarthritis. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion. Disagreements were discussed and resolved involving a third reviewer if required. Data were then extracted and the risk of bias of trials assessed. Main outcomes were blood loss, visual analogue score (VAS) pain, adverse events, knee range of motion, transfusion rate and knee function. Secondary outcomes were analgesia use, knee swelling, length of hospital stay, quality of life and activity level. Effects of interventions were estimated as mean differences (MD), standardised mean differences (SMD) or given as risk ratios (RR), with 95% confidence intervals (CI). Meta-analyses were performed using the inverse variance method and pooled using random effects. MAIN RESULTS: Eleven randomised trials and one controlled clinical trial involving 809 participants met the inclusion criteria. There is very low quality evidence from 10 trials (666 participants) that cryotherapy has a small benefit on blood loss (SMD -0.46, 95% CI, -0.84 to -0.08), equivalent to 225mL less blood loss in cryotherapy group (95% CI, 39 to 410mL). This benefit may not be clinically significant. There was very low quality evidence from four trials (322 participants) that cryotherapy improved visual analogue score pain at 48 hours (MD = -1.32 points on a 10 point scale, 95% CI, -2.37 to -0.27), but not at 24 or 72 hours. This benefit may not be clinically significant. There was no difference between groups in adverse events (RR = 0.98, 95% CI, 0.28 to 3.47). There is low quality evidence from two trials (107 participants) for improved range of motion at discharge (MD 11.39 degrees of additional flexion, 95% CI 4.13 to 18.66), but this benefit may not be clinically significant. There was no difference between groups in transfusion rate (RR 2.13, 95% CI 0.04 to 109.63), and knee function was not measured in any trial. No significant benefit were found for analgesia use, swelling or length of stay. Outcomes measuring quality of life or activity level were not reported. AUTHORS' CONCLUSIONS: Potential benefits of cryotherapy on blood loss, postoperative pain, and range of motion may be too small to justify its use, and the quality of the evidence was very low or low for all main outcomes. This needs to be balanced against potential inconveniences and expenses of using cryotherapy. Well designed randomised trials are required to improve the quality of the evidence.

Impact of the closure of a large urban medical center: a quantitative assessment (part II).

This community health needs assessment-the second part of a mixed-methods project-sought to quantitatively determine the impact of the closure of St. Vincent's Medical Center, a large not-for-profit hospital in NYC on individuals who used its services. Findings from a community survey disseminated to the broader community affected by the closure of this hospital are described. The questions covered topics including demographics, health status, experiences accessing health care pre- and post-hospital closure, access to medical records, prescriptions, etc. The majority of respondents are from the community immediately surrounding the hospital. Almost 50% report having a physical or mental health condition requiring regular care; roughly 64% had a doctor affiliated with St. Vincent's and 68% currently see the same doctor as before the hospital closed. With regard to service utilization, 74% reported having sought services at St. Vincent's in the past 5 years. Of these, the emergency department was the most commonly used service (75%), followed by specialty tests (32%), inpatient care (30%), and outpatient services (22%). The majority of ratings of services at St. Vincent's were "excellent" or "very good." Conversely, 65% of former St. Vincent's users reported more difficulty obtaining health care post closure. Of the 11% who have tried to access their medical records, 30% have not been able to obtain their records and 42% report their attempt as being "somewhat difficult" or "very difficult." Over 50% report spending more time traveling or traveling further to get to their healthcare provider; and over one third report waiting longer to get an appointment, or to be seen when at an appointment. Bivariate analyses revealed that certain subgroups of respondents had significantly worse negative experiences associated with the closure of the hospital. Specifically, individuals with a health condition were more likely to have visited an ER since St. Vincent's closed, and now travel further and spend more time traveling to their health care provider, compared to those without a physical and/or mental health condition. Similarly, a greater proportion of respondents who had a doctor affiliated with St. Vincent's reported greater challenges accessing care since the closing, compared to those who did not have a doctor affiliated with St. Vincent's (e.g., waiting longer to get an appointment). Finally, the same health care challenges were being experienced by those who are not seeing the same doctor as prior to the closing.

Impact of the closure of a large urban medical center: a qualitative assessment (part I).

This community health needs assessment-the first part of a mixed-methods project-sought to qualitatively examine the impact of the closure of St. Vincent's Catholic Medical Center, a large not-for-profit hospital in NYC, on individuals who used its services. Key informant interviews with organizational leaders and focus groups with residents were conducted to understand hospital utilization, unmet health care needs, health care utilization and experiences post closure, perceptions of the most significant effect of the closing, and recommendations for improving health care in the community. Most respondents spoke positively of the hospital's accessibility, comprehensive, high-quality services, and its close relationship with the community. Conversely, experiences post-closure were largely negative, including decreased access, interrupted care, and loss of emergency and specialty care. Lack of information concerning medical records reflected a larger problem of poor planning and community outreach. Another issue was widespread anxiety in a community now lacking a hospital. Further, while the hospital's closure might cause inconveniences, these effects were described as more daunting to vulnerable groups. Our findings provide a consistent picture of a hospital highly regarded by residents, patients, and leaders of several health and social services organizations. Regardless of whether it should have been permitted to close (as raised by many respondents), the lack of advance planning and outreach to community members and patients remains a major criticism. Coordinated efforts to provide the community with information about health and social services in the area will respond to a clear need while reducing some of the complexity encountered with utilizing local health care services.

Understanding Immune Responses to Viruses-Do Underlying Th1/Th2 Cell Biases Predict Outcome?

Emerging and re-emerging viral diseases have increased in number and geographical extent during the last decades. Examples include the current COVID-19 pandemic and the recent epidemics of the Chikungunya, Ebola, and Zika viruses. Immune responses to viruses have been well-characterised within the innate and adaptive immunity pathways with the outcome following viral infection predominantly attributed to properties of the virus and circumstances of the infection. Perhaps the belief that the immune system is often considered as a reactive component of host defence, springing into action when a threat is detected, has contributed to a poorer understanding of the inherent differences in an individual's immune system in the absence of any pathology. In this review, we focus on how these host factors (age, ethnicity, underlying pathologies) may skew the T helper cell response, thereby influencing the outcome following viral infection but also whether we can use these inherent biases to predict patients at risk of a deviant response and apply strategies to avoid or overcome them.

Role of chemotherapy in upper urinary tract urothelial cell cancers.

Urothelial cancers of the upper urinary tract are uncommon and often treated in a similar fashion to lower urinary tract urothelial malignancies. Currently, there are no clear guidelines on the use of systemic chemotherapy for upper urinary tract urothelial cancers either in the perioperative setting or in cases of advanced disease. The aim of this article is to review the key studies in upper urinary tract cancers to help develop an understanding about the optimal management and suggest areas for future research.

Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances.

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically "cold" tumour type. This provides an attractive niche for OV, given viruses have been shown to turn "cold" tumours "hot," thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

Single cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets.

Determining the epigenetic program that generates unique cell types in the kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profile open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. We show critical reliance of gene expression on distal regulatory elements (enhancers). We reveal key cell type-specific transcription factors and major gene-regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrates that podocyte commitment occurs early and is associated with sustained Foxl1 expression. Renal tubule cells follow a more complex differentiation, where Hfn4a is associated with proximal and Tfap2b with distal fate. Mapping single nucleotide variants associated with human kidney disease implicates critical cell types, developmental stages, genes, and regulatory mechanisms. The single cell multi-omics atlas reveals key chromatin remodeling events and gene expression dynamics associated with kidney development.

Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors.

Oncolytic viruses (OV) have been shown to activate the antitumor functions of specific immune cells like T cells. Here, we show OV can also reprogram tumor-associated macrophage (TAM) to a less immunosuppressive phenotype. Syngeneic, immunocompetent mouse models of primary breast cancer were established using PyMT-TS1, 4T1, and E0771 cell lines, and a metastatic model of breast cancer was established using the 4T1 cell line. Tumor growth and overall survival was assessed following intravenous administration of the OV, HSV1716 (a modified herpes simplex virus). Infiltration and function of various immune effector cells was assessed by NanoString, flow cytometry of dispersed tumors, and immunofluorescence analysis of tumor sections. HSV1716 administration led to marked tumor shrinkage in primary mammary tumors and a decrease in metastases. This was associated with a significant increase in the recruitment/activation of cytotoxic T cells, a reduction in the presence of regulatory T cells and the reprograming of TAMs towards a pro-inflammatory, less immunosuppressive phenotype. These findings were supported by in vitro data demonstrating that human monocyte-derived macrophages host HSV1716 replication, and that this led to immunogenic macrophage lysis. These events were dependent on macrophage expression of proliferating cell nuclear antigen (PCNA). Finally, the antitumor effect of OV was markedly diminished when TAMs were depleted using clodronate liposomes. Together, our results show that TAMs play an essential role in support of the tumoricidal effect of the OV, HSV1716-they both host viral replication via a novel, PCNA-dependent mechanism and are reprogramed to express a less immunosuppressive phenotype.

Methodologic approach to sampling and field-based data collection for a large-scale in-depth interview study: The Social Position and Family Formation (SPAFF) project.

Over the past several decades there have been dramatic shifts in demographic patterns pertaining to family formation, with declining and delayed marriage and childbearing, and increased cohabitation in the United States and other Western industrialized nations. These trends in family demography have been predominantly studied using large-scale datasets, which have identified total population and subgroup trends over time, including differences by age, gender, racial/ethnic, economic, educational, religious, and other characteristics. However, there is limited knowledge and understanding of how individuals across different levels of social position, as well as other important characteristics, make decisions around forming families. This lack of qualitative data on contemporary attitudes regarding family formation has hampered our ability to more completely understand the factors driving behaviors pertaining to the large-scale (ie, international) shifts in demographic trends. The Social Position and Family Formation (SPAFF) project is an in-depth interview study that used quantitative data to guide recruitment of a large sample for qualitative interview data collection on factors influencing different aspects of family formation among heterosexual females and males (18-35 years) in the context of individuals' social position. This methodological paper describes the use of a 'quantitatively-informed' purposive sampling approach in a large metropolitan area to collect qualitative data (through in-depth interviews) from a large sample (n = 200), utilizing web-based tools for successful community-based recruitment and project management.

Feasibility and Reliability of the System for Observing Play and Leisure Activity in Youth (SOPLAY) for Measuring Moderate to Vigorous Physical Activity in Children Visiting an Interactive Children's Museum Exhibition.

PURPOSE: To test the feasibility and reliability of a direct observation method for measuring moderate to vigorous physical activity (MVPA) in children visiting an interactive children's museum exhibition. DESIGN: Direct observation was used to assess MVPA in children visiting an interactive children's museum exhibition on 2 weekend days in winter 2013. SETTING: The Children's Museum of Manhattan's EatSleepPlay™: Building Health Every Day exhibition. PARTICIPANTS: Children (group level) visiting the museum exhibition. MEASURES: System for Observing Play and Leisure Activity in Youth (SOPLAY). ANALYSES: Interobserver reliability was analyzed for MVPA and activity type. Two-group analyses were conducted using a series of Wilcoxon rank sum tests. RESULTS: A total of 545 children were observed over 288 observations. No significant differences were found between observers for MVPA ( r = .91, P = .6804) or activity type (κ = .90, P = .6334). Children participated in MVPA during 35.2% of all observations. No significant differences were found for participation in MVPA between boys (37.6%) and girls (32.8%, P = .1589). CONCLUSION: The SOPLAY may be a useful tool for measuring MVPA in interactive children's museum exhibitions. Research with multiple museum settings and diverse groups of children over longer periods of time is warranted to further establish the feasibility and reliability of the SOPLAY for measuring MVPA in this novel setting.