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OBJECTIVE: We aimed to identify the barriers and enablers that Health Care Workers (HCWs) in Papua New Guinea experienced in swabbing for COVID-19. METHODS: We conducted a cross-sectional multi-methods study: a qualitative scoping exercise and a telephone survey. The target population was COVID-19-trained HCWs from all provinces of Papua New Guinea. A descriptive analysis of survey responses was conducted alongside a rapid qualitative analysis of interviews and open-ended survey questions. RESULTS: Four thematic areas were identified: human resources, logistics, HCW attitudes and community attitudes. The survey response rate was 70.3% (407/579). Commonly reported barriers to COVID-19 swabbing were insufficient staff trained (74.0%, n = 301), inadequate staffing in general (64.9%, n = 264), insufficient supply of personal protective equipment (60.9%, n = 248) and no cold chain to store swabs (57.5%, n = 234). Commonly reported enablers to swabbing were community awareness and risk communication (80.8%, n = 329), consistent and sufficient supplies of personal protective equipment (67.8%, n = 276), increased surge workforce (63.9%, n = 260) and having a fridge to store swabs (59.7%, n = 243). CONCLUSIONS: A comprehensive community and HCW engagement strategy combined with innovations to improve the supply chain are needed to increase COVID-19 swabbing in Papua New Guinea to reach national testing targets. Investments in increasing numbers of frontline workforce, consistent supplies of PPE, swabs, transport medium, cold boxes and ability to make ice packs, in addtion to establishing regular tranport of specimens from the facility to the testing site will strengthen the supply chain. Innovations are needed to address these issues.

This article examines small scale green spaces developed on underutilised land in the inner city, looking at the ways in which familiar domestic outdoor design characteristics have been used for placemaking in what is essentially a commercial setting. Using case studies situated in Adelaide, South Australia, this research explores both the development and characteristics of small commercial or community inner city green spaces, how they have aided revitalisation through imaginative treatments of leftover spaces, and the integration of stories and nostalgia in place creation. One of the potential benefits of nurturing such small scale green interventions in our cities are the impacts on wellbeing, not only for those who are resident in the city, but also for those who work there, study in or visit the city. The focus of the article is an investigation of how three case studies – a café, a bar and a community garden – have brought a sense of home into the commercial centre of the city, specifically in terms of the placemaking and urban design moves that have been employed. Refereed/Peer-reviewed

This chapter seeks to improve cultural and linguistic competence by focusing on how organizations and systems can further equity, diversity and inclusion (EDI) practices to ensure access to treatment and improve outcomes for diverse populations. The chapter begins with an introduction to the concepts and definitions of equity, diversity, inclusion and cultural competence, and then explains the importance of understanding racism and trauma. Strategies to address structural racism and historical trauma are provided, with the goal of educating service providers and program developers, using the concepts of cultural humility and sensitivity. The chapter also identifies examples of skills necessary to best serve youth and their families who have limited language proficiency, those who are deaf or hard of hearing, youth that identify as LGBT, and youth with a co-occurring developmental/intellectual and behavioral health disability. Program strategies and recommendations for these populations are provided. Finally, the chapter reviews what other child-serving systems (e.g., child welfare, juvenile justice) have done to address EDI, and how best practices can be adopted broadly when working with diverse youth and families who have unique needs.

This chapter and book begins with a family member story about the birth of the Building Bridges Initiative (BBI) at the original summit in 2006, and how the “parent and youth takeover” of the meeting changed the dynamic and created “a day of reckoning” that resulted in residential and community providers present committing to values and principles that subsequently became the BBI Joint Resolution. The chapter also provides background and context for the current work, including the recently passed Family First Prevention Services Act (FFPSA), and recommendations for how to use this volume to stimulate discussion, dialogue and innovation.

This chapter provides a comprehensive review of effective financing options for states, counties, and providers to implement the Building Bridges Initiative (BBI) framework and best practices needed to achieve sustained positive outcomes for youth and families receiving residential intervention. The authors conceptualize the residential transformation to come as “the new frontier” and provide readers with a detailed multi-page BBI Best Practice Fiscal Strategies Check List. The checklist is a compilation of the actions or strategies that leaders can use to create sustained positive change consistent with BBI. The Family First Prevention Services Act of 2018, which is a significant tool for child welfare programming, is reviewed in detail. Additional funding strategies for oversight agencies and provider agencies along with specific examples of strategy implementation are also discussed. Besides funding options for residential intervention, funding to promote alternatives to residential treatment and short-term placements is also considered. The authors predict the vastness of the new frontier will yield many more fiscal strategies that have yet to be conceived.

Papua New Guinea (PNG) faces a critical shortage of human resources to address pressing public health challenges arising from an increasing burden of communicable and non-communicable diseases. PNG is an independent State in the Pacific and home to 8.2 million people. Resource and infrastructure constraints due to the country’s challenging geography have made it difficult and expensive to deliver health services and implement health programmes. The National Department of Health and its partners developed a field epidemiology training programme of Papua New Guinea (FETPNG) to strengthen the country’s public health workforce. The training programme covers field epidemiology competencies and includes the design, implementation and evaluation of evidence-based interventions by Fellows. From 2013 to 2018, FETPNG graduated 81 field epidemiologists. Most FETPNG graduates (84%) were from provincial or district health departments or organisations. Many of their intervention projects resulted in successful public health outcomes with tangible local impacts. Health challenges addressed included reducing the burden of multi-drug resistant-tuberculosis (TB), increasing immunisation coverage, screening and treating HIV/TB patients, and improving reproductive health outcomes. FETPNG Fellows and graduates have also evaluated disease surveillance systems and investigated disease outbreaks. Early and unwavering national ownership of FETPNG created a sustainable programme fitting the needs of this low-resource country. A focus on designing and implementing effective public health interventions not only provides useful skills to Fellows but also contributes to real-time, tangible and meaningful improvements in the health of the population. The graduates of FETPNG now provide a critical mass of public health practitioners across the country. Their skills in responding to outbreaks and public health emergencies, in collecting, analysing and interpreting data, and in designing, implementing and evaluating public health interventions continues to advance public health in PNG.

Background HuMax-IL8 (now known as BMS-986253) is a novel, fully human monoclonal antibody that inhibits interleukin-8 (IL-8), a chemokine that promotes tumor progression, immune escape, epithelial-mesenchymal transition, and recruitment of myeloid-derived suppressor cells. Studies have demonstrated that high serum IL-8 levels correlate with poor prognosis in many malignant tumors. Preclinical studies have shown that IL-8 blockade may reduce mesenchymal features in tumor cells, making them less resistant to treatment. Methods Fifteen patients with metastatic or unresectable locally advanced solid tumors were enrolled in this 3 + 3 dose-escalation trial at four dose levels (4, 8, 16, or 32 mg/kg). HuMax-IL8 was given IV every 2 weeks, and patients were followed for safety and immune monitoring at defined intervals up to 52 weeks. Results All enrolled patients (five chordoma, four colorectal, two prostate, and one each of ovarian, papillary thyroid, chondrosarcoma, and esophageal) received at least one dose of HuMax-IL8. Eight patients had received three or more prior lines of therapy and five patients had received prior immunotherapy. Treatment-related adverse events occurred in five patients (33%), mostly grade 1. Two patients receiving the 32 mg/kg dose had grade 2 fatigue, hypophosphatemia, and hypersomnia. No dose-limiting toxicities were observed, and maximum tolerated dose was not reached. Although no objective tumor responses were observed, 11 patients (73%) had stable disease with median treatment duration of 24 weeks (range, 4–54 weeks). Serum IL-8 was significantly reduced on day 3 of HuMax-IL8 treatment compared to baseline (p = 0.0004), with reductions in IL-8 seen at all dose levels. Conclusions HuMax-IL8 is safe and well-tolerated. Ongoing studies are evaluating the combination of IL-8 blockade and other immunotherapies. Trial registration NCTN, NCT02536469. Registered 23 August 2015, https://clinicaltrials.gov/ct2/show/NCT02536469?term=NCT02536469&rank=1. Electronic supplementary material The online version of this article (10.1186/s40425-019-0706-x) contains supplementary material, which is available to authorized users.

δ-Tocopherol (δ-T), the least prevalent tocopherol in our diet, was described to have a more potent anticancer activity in solid tumors compared to the other tocopherols. δ-T induces tumor cell death through peroxisome proliferator-activated receptor γ (PPAR-γ) induction, cyclin-D1 inhibition, and modulation of redox balance. Nevertheless, the role of δ-T in preventing or treating hematologic malignancies has not been studied. In this study, we screened the efficacy of δ-T against six cell lines representing a wide spectrum of hematologic malignancies: Jurkat (acute T-cell leukemia), K-562 (chronic myeloid leukemia), KG-1 [acute myeloid leukemia (AML)], THP-1 (acute monocytic leukemia), TOM-1 (acute lymphoblastic leukemia), and UMCL01-101 (AIDS-associated diffuse large B-cell lymphoma). Interestingly, the AML cell line KG-1 was the only one to be significantly affected at concentrations of δ-T as low as 20 µM. The antileukemic activity of δ-T in AML was verified in a set of primary cells collected from patients newly diagnosed with AML. Apoptotic induction and cell cycle arrest explained the efficacy of δ-T against KG-1 cells. The mechanism of cell growth inhibition of δ-T was through downregulation of cyclin-D1 and a set of homeobox proteins (HOXA9, PBX1, and Cdx2) that have a well-documented role in the pathobiology of AML.

Lessons Learned Modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury followed by fowlpox virus-BN-Brachyury was well tolerated upon administration to patients with advanced cancer. Sixty-three percent of patients developed CD4+ and/or CD8+ T-cell responses to brachyury after vaccination. BN-Brachyury vaccine also induced T-cell responses against CEA and MUC1, which are cascade antigens, that is, antigens not encoded in the vaccines. Background Brachyury, a transcription factor, plays an integral role in the epithelial–mesenchymal transition, metastasis, and tumor resistance to chemotherapy. It is expressed in many tumor types, and rarely in normal tissues, making it an ideal immunologic target. Bavarian Nordic (BN)-Brachyury consists of vaccination with modified vaccinia Ankara (MVA) priming followed by fowlpox virus (FPV) boosting, each encoding transgenes for brachyury and costimulatory molecules. Methods Patients with metastatic solid tumors were treated with two monthly doses of MVA-brachyury s.c., 8 × 108 infectious units (IU), followed by FPV-brachyury s.c., 1 × 109 IU, for six monthly doses and then every 3 months for up to 2 years. The primary objective was to determine safety and tolerability. Results Eleven patients were enrolled from March 2018 to July 2018 (one patient was nonevaluable). No dose-limiting toxicities were observed. The most common treatment-related adverse event was grade 1/2 injection-site reaction observed in all patients. Best overall response was stable disease in six patients, and the 6-month progression-free survival rate was 50%. T cells against brachyury and cascade antigens CEA and MUC1 were detected in the majority of patients. Conclusion BN-Brachyury vaccine is well tolerated and induces immune responses to brachyury and cascade antigens and demonstrates some evidence of clinical benefit.

Introduction: Influenza-associated severe acute respiratory infections (SARI) are a major contributor to global morbidity and mortality. In response to a cluster of SARI cases and deaths in pregnant women, with two deceased cases testing positive for influenza A(H1N1) pdm09, an investigation was initiated to determine whether there was an increase of paediatric SARI cases admitted to divisional hospital intensive care units in Fiji in may 2016 compared to May 2013-2015. Methods: Retrospective case finding was conducted at the paediatric intensive care units (PICUs) in Fiji's three divisional hospitals. Data were collected from 1 January 2013 to 26 May 2016. Cases were identified using a list of clinical diagnoses compatible with SARI. Results: A total of 632 cases of paediatric SARI with complete details were identified. The median age of cases was 6 months (Interquartile range: 2-14 months). Children aged less than 5 years had a higher rate of paediatric SARI requiring admission to a divisional hospital PICU in May 2016 compared to May 2013-2015 (Incidence rate ratio: 1.7 [95% CI: 1.1-2.6]). This increase was not observed in children aged 5-14 years. The case-fatality ratio was not significantly different in 2016 compared to previous years. Conclusion: The investigation enabled targeted public health response measures, including enhanced SARI surveillance at divisional hospitals and an emergency influenza vaccination campaign in the Northern Division.

INTRODUCTION: Multiple immune checkpoint inhibitors (ICIs) that modulate immune cells in the periphery and the tumor microenvironment (TME) have been approved, as have the therapeutic cancer vaccines sipuleucel-T for metastatic castration-resistant prostate cancer and talimogene laherparepvec (T-VEC) for metastatic melanoma. These developments provide rationale for combining these modalities to improve response rates and durability of responses in a variety of cancers. Preclinical data have shown that vaccines can induce immune responses that turn a tumor from ‘cold’ to ‘hot,’ but vaccines do not appear to be highly active as monotherapy. AREAS COVERED: Here, we provide a review of the current state of vaccine and ICI combination studies. EXPERT COMMENTARY: Most combination trials are in early phases, but several are now in phase III. Vaccines that target antigens expressed exclusively on tumor cells, neoantigens, have the potential to induce robust antitumor responses. Several techniques for predicting which neoepitopes to target, based on tumor mutational profiling, are in various stages of development. To be successful, combination immunotherapy approaches must seek to prime the immune system, expand the immune response, and facilitate immune function within the TME.

To assess the performance of an early warning, alert and response system (EWARS) developed by the World Health Organization (WHO) - EWARS in a Box - that was used to detect and control disease outbreaks after Cyclone Winston caused destruction in Fiji on 20 February 2016.Immediately after the cyclone, Fiji's Ministry of Health and Medical Services, supported by WHO, started to implement EWARS in a Box, which is a smartphone-based, automated, early warning surveillance system for rapid deployment during health emergencies. Both indicator-based and event-based surveillance were employed. The performance of the system between 7 March and 29 May 2016 was evaluated. Users' experience with the system was assessed in interviews using a semi-structured questionnaire and by a cross-sectional survey. The system's performance was assessed using data from the EWARS database.Indicator-based surveillance recorded 34 113 cases of the nine syndromes under surveillance among 326 861 consultations. Three confirmed outbreaks were detected, and no large outbreak was missed. Users were satisfied with the performance of EWARS and judged it useful for timely monitoring of disease trends and outbreak detection. The system was simple, stable and flexible and could be rapidly deployed during a health emergency. The automated collation, analysis and dissemination of data reduced the burden on surveillance teams, saved human resources, minimized human error and ensured teams could focus on public health responses.In Fiji, EWARS in a Box was effective in strengthening disease surveillance during a national emergency and was well regarded by users.Évaluer les performances du système d'alerte et d'intervention rapides conçu par l'Organisation mondiale de la Santé (OMS) baptisé « Immédiatement après le passage du cyclone, le ministère de la Santé et des Services médicaux, avec l'aide de l'OMS, a déployé le systèmeLa surveillance effectuée sur la base des indicateurs a donné lieu au signalement de 34 113 cas correspondant à la définition des neuf syndromes surveillés, sur un total de 326 861 consultations. Trois flambées épidémiques confirmées ont été détectées et aucune flambée majeure n'a échappé à la surveillance. Les utilisateurs se sont dits satisfaits des performances du systèmeÀ Fidji, le systèmeEvaluar el funcionamiento de un sistema de alerta temprana, alerta y respuesta (EWARS, por sus siglas en inglés) desarrollado por la Organización Mundial de la Salud (OMS), EWARS in a Box, que se utilizó para detectar y controlar los brotes de enfermedades después de que el ciclón Winston causara destrucción en Fiji el 20 de febrero de 2016.Inmediatamente después del ciclón, el Ministerio de Salud y Servicios Médicos de Fiji, con el apoyo de la OMS, comenzó a aplicar el sistema EWARS in a Box, que es un sistema de vigilancia de alerta temprana automatizado y basado en teléfonos inteligentes para un despliegue rápido durante las emergencias sanitarias. Se recurrió tanto a la vigilancia basada en indicadores como en eventos. Se evaluó el funcionamiento del sistema entre el 7 de marzo y el 29 de mayo de 2016. La experiencia de los usuarios con el sistema se evaluó en entrevistas mediante un cuestionario semiestructurado y una encuesta transversal. El rendimiento del sistema se evaluó utilizando datos de la base de datos EWARS.La vigilancia basada en indicadores registró 34.113 casos de los nueve síndromes bajo vigilancia, entre 326.861 consultas. Se detectaron tres brotes confirmados y ningún brote serio fue detectado. Los usuarios se mostraron satisfechos con el rendimiento del EWARS y lo consideraron útil para el seguimiento oportuno de las tendencias de enfermedades y la detección de brotes. El sistema era sencillo, estable y flexible y podía desplegarse rápidamente durante una emergencia sanitaria. La recopilación, el análisis y la difusión automatizados de datos redujo la carga de los equipos de vigilancia, ahorró recursos humanos, minimizó los errores humanos y garantizó que los equipos pudieran centrarse en las respuestas de sanidad pública.En Fiji, EWARS in a Box fue efectivo en el fortalecimiento de la vigilancia de enfermedades durante una emergencia nacional y fue bien considerado por los usuarios.تقييم أداء نظام الإنذار المبكر والإنذار والاستجابة (EWARS)، الذي طورته منظمة الصحة العالمية (EWARS in a Box)، والذي تم استخدامه لاكتشاف ومكافحة تفشي الأمراض بعد ما تسبب فيه إعصار وينستون من تدمير في فيجي، في 20 فبراير/شباط 2016.بعد وقوع الإعصار مباشرة، بدأت وزارة الصحة والخدمات الطبية في فيجي، بدعم من منظمة الصحة العالمية، في تنفيذ نظام EWARS in a Box، وهو نظام آلي للمراقبة والإنذار المبكر يعتمد على الهاتف الذكي، وذلك من أجل الانتشار السريع أثناء الطوارئ الصحية. تم استخدام كل من المراقبة المستندة إلى المؤشر والمستندة على الحدث. تم تقييم أداء النظام بين 7 مارس/آذار و29 مايو/أيار 2016. تم تقييم تجربة المستخدمين مع النظام في مقابلات شخصية باستخدام استبيان شبه منظم ومسح مقطعي. تم تقييم أداء النظام باستخدام بيانات من قاعدة بيانات EWARS.سجلت المراقبة المستندة إلى المؤشر 34113 حالة من المتلازمات التسع تحت المراقبة بين 326861 استشارة. تم الكشف عن ثلاث حالات تفشي مؤكدة، ولم يتم تفويت أي تفش كبير. أعرب المستخدمون عن ارتياحهم لأداء نظام EWARS واعتبروا أنه مفيد لرصد اتجاهات الأمراض والكشف عن التفشي في الوقت المناسب. كان النظام بسيطًا ومستقرًا ومرنًا ويمكن نشره بسرعة أثناء الطوارئ الصحية. وقد أدى الجمع الآلي وتحليل البيانات ونشرها إلى تقليل العبء الواقع على فرق المراقبة، والموارد البشرية المحفوظة، والحد الأدنى من الأخطاء البشرية ، كما ضمنت للفرق أن تركز على استجابات الصحة العامة.كان نظام EWARS in a Box في فيجي فعالاً في تعزيز مراقبة الأمراض خلال حالات الطوارئ الوطنية، وكان محل تقدير من المستخدمين.旨在评估世界卫生组织开发的早期预警、警报和响应系统 (EWARS in a Box) 的性能，其被用于检测和控制 2016 年 2 月 20 日温斯顿飓风在斐济大规模破坏后的疾病爆发。.飓风侵袭后，斐济卫生和医疗服务部在世界卫生组织的支持下，开始实施早期预警、警报和响应系统 (EWARS in a Box)，这是一个基于智能手机、自动化的早期预警监控系统，可用于卫生紧急状态下的快速部署。采用基于指标和基于事件的监测方法。对 2016 年 3 月 7 日至 5 月 29 日期间的系统性能进行了评估。在访谈中，我们使用半结构式问卷和横断面调查，评估使用该系统用户的用户体验。使用早期预警、警报和响应系统 (EWARS) 数据库的数据来评估系统性能。.基于指标的监测记录了在 326861 次咨询中，9 种综合症状，共 34113 个病例得以监测。已检测到三次证实的突发疾病，没有错失任何大规模的疾病爆发。用户对早期预警、警报和响应系统 (EWARS) 的性能表示满意，认为其有助于及时监测疾病趋势和疾病爆发。该系统简单、稳定、灵活，可在卫生紧急状态下快速进行部署。数据的自动整理、分析和传播能减轻监测小组的负担，节省人力资源，最大限度地减少人为错误，确保监测小组能够专注于公共卫生响应。.在斐济，早期预警、警报和响应系统 (EWARS in a Box) 能有效加强国家卫生紧急状态下的疾病监测，并受到用户的好评。.Оценка качества работы системы раннего предупреждения, оповещения и реагирования (early warning, alert and response system, EWARS), разработанной Всемирной организацией здравоохранения (ВОЗ), в пакетном варианте, которая использовалась для выявления и контроля вспышек заболеваний после разрушений, вызванных циклоном «Уинстон» на островах Фиджи 20 февраля 2016 года.Незамедлительно после циклона Министерство здравоохранения и медицинского обслуживания Фиджи при поддержке ВОЗ стало внедрять пакетный вариант EWARS, представляющий собой автоматическую систему мониторинга раннего предупреждения на базе смартфонов, предназначенную для быстрого развертывания в ситуациях внезапной угрозы здоровью населения. Мониторинг осуществлялся на основе индикаторов и событий. Оценка работы системы проводилась в период с 7 марта по 29 мая 2016 года. Опыт эксплуатации системы оценивался в ходе собеседований с использованием частично структурированных анкет и в ходе перекрестного опроса. Качество работы системы оценивалось с использованием информации, хранимой в базе данных EWARS.Мониторинг на основе индикаторов позволил выявить 34 113 случаев девяти наблюдаемых синдромов в ходе 326 861 консультации. Были обнаружены и подтверждены три вспышки, и ни одна крупная вспышка не была упущена. Пользователи были довольны качеством работы системы EWARS и нашли ее полезной для своевременного мониторинга динамики распространения и выявления вспышек заболеваний. Система оказалась простой, стабильной и гибкой, и в случае чрезвычайных ситуаций в сфере здравоохранения ее можно быстро задействовать. Автоматическая сводка, анализ и распространение данных позволили разгрузить группы осуществления мониторинга, сэкономить людские ресурсы, свести к минимуму человеческие ошибки и сосредоточиться ликвидаторам на ответных мерах в системе здравоохранения.На островах Фиджи пакетная система EWARS позволила эффективно укрепить систему мониторинга заболеваний в ходе национального природного бедствия и получила хорошую оценку пользователей.

Therapeutic cancer vaccines have gained significant popularity in recent years as new approaches for specific oncologic indications emerge. Three therapeutic cancer vaccines are FDA approved and one is currently approved by the EMA as monotherapy with modest treatment effects. Combining therapeutic cancer vaccines with other treatment modalities like radiotherapy (RT), hormone therapy, immunotherapy, and/or chemotherapy have been investigated as a means to enhance immune response and treatment efficacy. There is growing preclinical and clinical data that combination of checkpoint inhibitors and vaccines can induce immunogenic intensification with favorable outcomes. Additionally, novel methods for identifying targetable neoantigens hold promise for personalized vaccine development. In this article, we review the rationale for various therapeutic combinations, clinical trial experiences, and future directions. We also highlight the most promising developments that could lead to approval of novel therapeutic cancer vaccines.

2640 Background: Brachyury, a transcription factor, plays an integral role in epithelial-to-mesenchymal transition, metastasis, poor prognosis, and resistance to chemotherapy. It is expressed in many tumor types, and rare in normal tissue, making it an ideal immunologic target. BN-Brachyury comprises heterologous vaccination with recombinant MVA priming followed by FPV boosting, each encoding transgenes for brachyury and three costimulatory molecules (B7-1, ICAM1, and LFA-3). Heterologous prime boost approach is intended to optimize immunogenicity, as previously observed. Methods: Pts with metastatic solid tumors were treated with 2 monthly doses of MVA-brachyury SC at the previously tested dose, 2.2 x 109 infectious units (IU), followed by FPV-brachyury SC, 1 x 109 IU, for 6 monthly doses and then every 3 months for up to 2 years. The primary objective was to determine safety and tolerability and establish the RP2D. Immune assays were conducted to evaluate immunogenicity. Results: In 10 pts (3 chordoma, 6 GI, 1 papillary thyroid), no dose-limiting toxicities or serious treatment-related adverse events (TRAEs) were observed. The only Grade 3 TRAE was sedation associated with fever, which resolved spontaneously and did not recur with subsequent cycles. All other TRAEs were Grade 1 or 2; the most common was injection-site reaction in all patients. Five pts have had stable disease for > 24 wks (per RECIST v1.1) and remain on treatment. One pt with chordoma, for which BN-Brachyury was granted orphan drug designation, has had a 13.2% reduction in tumor size. As previously demonstrated, brachyury-specific T cell responses were observed, as were responses against cascade antigens (non-encoded antigens) CEA and MUC-1. Conclusions: Heterologous MVA- and FPV-brachyury is well tolerated and induced immune responses to brachyury and cascade antigens, suggesting induction of immunologically relevant tumor cell destruction. These data have informed combining BN-Brachyury with checkpoint inhibition (NCT03493945) and radiation (NCT03595228) to evaluate potential for synergetic activity in selected populations. Clinical trial information: NCT03349983.

Purpose To assess the effect of echo-sampling strategy on the accuracy of out-of-phase (OP) and in-phase (IP) multi-echo gradient-echo magnetic resonance imaging (MRI) hepatic fat fraction (FF) estimation, using MR spectroscopy (MRS) proton density FF (PDFF) as a reference standard.

Tertius iungens brokerage is unique within the dominant brokerage conceptualizations in sociology. While most brokerage research finds that brokers reap rewards from mediating relationships in ways that keep actors apart, iungens research finds that brokers can have an interest in joining previously disconnected actors and sustaining these relationships. This paper expands the explanatory potential of iungens brokerage by building a multidimensional theoretical framework that explains transnational connecting processes, generating insights beyond the traditional focus on network structures into the under-researched area of brokerage across institutions. The paper synthesizes streams of brokerage research that have developed in relative isolation from each other to elucidate how organizational brokers and their staffs create transnational structural and cognitive connections that draw actors together into intersectoral networks that cross two or more nationally organized regulatory regimes and cultural systems in order to cooperate on complex public good problems. The paper’s case study of public health cooperation on the United States–Mexico border advances the argument that iungens brokerage is necessary to counter the divisive effects that state institutions tend to exert on transnational networks over time.

Hepatic Fibrosis, the progressive deposition of collagen in the extracellular matrix of the liver, is a fundamental alteration of liver parenchyma in many chronic liver diseases. It impairs liver function, may lead to cirrhosis and hepatocellular carcinoma, and constitutes an important cause of morbidity, mortality, and health care costs (1–4). Early diagnosis is important to initiate treatment and halt progression. Biopsy is the current gold standard for diagnosis, but it is expensive and invasive—factors that limit utility in longitudinal assessments (5–16). The limitations of biopsy for longitudinal assessment have impeded progress in clinical care and research of diffuse liver diseases associated with hepatic fibrosis. There is a need to develop noninvasive imaging techniques that can safely diagnose fibrosis. Conventional ultrasound, computed tomography, and magnetic resonance imaging (MRI) can assess gross liver morphology, or contour, to confirm cirrhosis in patients with advanced liver disease, but such an assessment is insensitive to the early stages of fibrosis and cirrhosis (6,17–19). An alternative imaging-based approach to evaluate hepatic fibrosis is to assess internal liver architecture, or texture. Texture can be defined as a complex visual pattern within an image that consists of simpler subpatterns with characteristic features (20). These features can be assessed objectively by quantitative texture analysis (TA). Quantitative TA has been used to noninvasively classify the liver in a dichotomous fashion as normal or cirrhotic on unenhanced MR images (21,22). In a study with 13 healthy volunteers and 5 cirrhotic patients, quantitative TA of high spatial resolution T2-weighted images provided 100% sensitivity and specificity for discrimination between normal volunteers and cirrhotic patients (21). In another study of 43 cirrhotic patients and 10 normal volunteers, quantitative TA on unenhanced T2-weighted MR images classified patients as cirrhotic or normal with a misclassification rate of 8% (22). Both studies used a publicly available, free software program (MaZda, v. 3.20, Instytut Elektroniki Politechnika, Lodza, Poland) to compute TA parameters from liver images and to generate multivariate predictive models from the parameters (23–25). Because double contrast-enhanced MRI shows fibrosis with greater clarity than unenhanced imaging (26–30), we hypothesized that quantitative TA of double contrast-enhanced MRI may permit accurate dichotomous classification of fibrosis in clinical patients with a spectrum of fibrosis severity, not just discrimination between healthy volunteers versus patients with cirrhosis. The purpose of this pilot, retrospective study was to demonstrate proof of concept that noninvasive quantitative TA on double contrast-enhanced MR liver images can classify liver fibrosis dichotomously in clinical patients, using histology as the reference standard. We used the same software program used in prior studies (MaZda) to compute TA parameters and applied statistical techniques to develop classification models based on the TA parameters.

The child welfare system operates as a joint endeavor of the public and private sectors, while in each state the roles of the sectors and the functioning of their relationship varies across a continuum. The system and the sectors operating within it face both facilitators and challenges as they face a future of serving children and families. In this article, leaders from national organizations with differing constituencies who operate as stakeholders in the child welfare system write essays on their perspectives on the future of public–private partnership in child welfare: the state agency; private providers; the courts; the frontline practitioner; the consumer; and the public and their policy-makers.

3091Background: BMS-986253 is a novel fully human monoclonal antibody that binds to and inhibits IL-8, a chemokine that promotes immune escape and tumor progression. High serum IL-8 levels correlat...

SUMMARY Thirty-seven of 43 (86%) agencies operating child welfare residential treatment centers in New York State responded to a survey about the provision of mental health services. Questions were asked about provision of services, satisfaction with services, and suggestions for improvement in five domains: therapeutic milieu, individual therapy, group therapy, family therapy, and psychiatric services. Results revealed that due to funding constraints most agencies reported hiring direct care staff with limited formal education to work with children who present with increasing intensity and severity of emotional and behavioral problems, which in part led to high turnover rates and moderate levels of satisfaction with services. Taken together, the data highlight the demands on the system as more severely troubled youth are being served with fewer dollars provided for their care. The findings suggest many avenues for advocacy, clinical intervention, staff development, and further research.

During the period following WWII, the provision of housing was a primary concern for both architects and the general public. Architects believed there was a need to make their services more widely available. They did this by providing a plans service of contemporary designs for affordable houses, called the Small Homes Service (SHS) of South Australia. The SHS reached out to the public through media such as newspapers, magazines, the radio and displays in department stores and showgrounds. This article explains how the architectural profession saw its role in contributing to the improvement of the standard of small house design and details the aims, operations, designs and achievements of the SHS. The significance of the SHS was not only in its built output but also in its contribution to the education of the general public regarding contemporary architectural design.

As an incidental finding in paraffin sections of brain tissue used as positive controls for synaptophysin immunostain, the cytoplasm of choroid plexus epithelium present was found to stain strongly positively for this substance. This was subsequently found to be the case in normal choroid plexuses in autopsy material from infancy to old age, as well as in epithelial cells of papillomas and carcinomas of the choroid plexus. The latter findings may prove useful in differentiating choroid plexus carcinomas from metastatic papillary carcinomas of extracerebral origin with the exception of neuroendocrine carcinomas of various sites that are usually positive for synaptophysin.

Objective: We analyzed the histologic and immunohistochemical changes in the endometrial leukocytic subpopulations to determine which of them are characteristic of chronic endometritis. Results: Endometrial biopsies from 25 cases of chronic endometritis and 35 controls were studied. Characteristic morphologic findings included the presence of a plasma cell infiltrate, and a prominent, albeit non-specific, lymphocytic infiltrate in all patients with endometritis. A neutrophilic infiltrate was also noted in 90% of the patients. Other non-specific histologic findings included occasional prominent lymphoid aggregates, stromal edema, hemorrhage, and necrosis and cystic dilation of some glands in endometria of patients with chronic endometritis. Endometrial immune cells were investigated immunohistochemically using antibodies to CD3 (pan-T), CD20 (pan-B, L26), and Ham-56 (macrophage). In control patients, endometrial immune cells were predominantly composed of CD3 and Ham-56 positive cells. CD20 positive cells comprised

As the open-air sanatorium movement gained popularity during the nineteenth century, the therapeutic benefits of place were promoted in the crusade against tuberculosis by both medical professionals and architects. Fresh air, isolation, hygiene, discipline and education in a non-urban environment at high altitude were seen to be the keys to successful open-air treatment at sanatoria around the world. However, open-air sanatoria in Australia were not only therapeutic places, they were instruments of prevention. This article examines Australian tuberculosis sanatoria designed on the open-air treatment principles from 1895 to 1910. It focuses predominantly on Kalyra and Nunyara, both at Belair, South Australia, and the Queen Victoria Home for Consumptives at Wentworth Falls, New South Wales. In doing so, it explores the contribution of the buildings and landscape to the machinery of health as both an instrument of cure and prevention. Refereed/Peer-reviewed

This paper arose in response to observing the frustration expressed by researchers that there were so few accessible documents from which to write biographies of early women architects, planners and designers. As an archivist, it is a disheartening experience to explain to users that, because of limited donations, few such records exist in archival collections. Exemplifying the current predicament is the absence of the architectural work of the first woman officially qualified in South Australia, Beverly Bolin, from any archival collection in her own name. Moreover, extant items that were uncovered about Beverley Bolin, following months of searching, spoke more of her personal, than of her professional life. This led to the question: where are the professional records of women architects and why have they not donated their records to archival repositories? Through a survey of literature and the author’s own direct observation as manager of an archival collection specialising in architecture, this paper discusses possible reasons and offers potential strategies to attract future donations. Refereed/Peer-reviewed

During a time of war, the federal government passed the National Fitness Act 1941 to improve the fitness of the youth of Australia and better prepare them for roles in the armed services and industry. Implementation of the National Fitness Act made federal funds available at a local level through state-based national fitness councils, which coordinated promotional campaigns, programs, education and infrastructure for physical fitness, with volunteers undertaking most of the work. Specifically focused on children and youth, national fitness councils supported the provision of children’s playgrounds, youth clubs and school camping programs, as well as the development of physical education in schools and its teaching and research in universities. By the time the Act was repealed in 1994, fitness had become associated with leisure and recreation rather than being seen as equipping people for everyday life and work. The emergence of the Australian National Preventive Health Agency Act 2010 offers the opportunity to reflect on synergies with its historic precedent. Refereed/Peer-reviewed

Open plan living spaces have become ubiquitous in Australian housing today. These spaces gained popularity during the 1950s and 1960s, yet the reasons behind their enthusiastic adoption by many post-war families have remained under-explored. A determining factor in the introduction and acceptance of open plan living may be traced to dominant cultural ideas about the family and the role of the child, which not only allowed these architectural shifts but demanded them. This article considers how house design was influenced by the prevailing understandings of childrearing following the Second World War through the examination of 1950s South Australian architect designed house plans.

Purpose: To assess the effects of intravenous gadolinium (Gd) and flip angle (FA) on liver fat quantification by opposed-phase (OP) and in-phase (IP) imaging. Materials and Methods: Our Institutional Review Board (IRB) approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant, retrospective, clinical study. We identified 79 patients in whom abdominal OP and IP gradient-echoes were obtained at 1.5T before and after Gd administration. All 79 patients were imaged at high FA (70°); 57 were also imaged at low FA (20°). Fat signal fraction (FSF) was calculated from pre- and post-Gd liver images for each subject and FA using the formula, FSF (SIP –S OP)/2SIP, where SIP and SOP are the OP and IP signal intensities, respectively. The dataset pairs (pre-Gd vs. post-Gd; high-FA vs. low-FA) were compared using linear regression analysis. Results: Before Gd, FSF was significantly greater at high FA than at low FA, with regression parameters (slope/intercept) of 1.27*/0.02*, where * indicates P value 0.01. After Gd, FSF was similar at high and low FA (0.99/– 0.00). Gd administration caused an FA-dependent reduction in FSF, larger at high FA (0.68*/– 0.03*) than at low FA (0.94, – 0.01*). Conclusion: FSF by OP-IP imaging is highly dependent on FA before Gd, but this dependency is eliminated after administration of Gd. Gd appears to minimize the effect of T1-weighting and may improve the accuracy of liver fat

Traditional prognostic indicators for astrocytic tumors include tumor size, type, and histologic grade. Data suggest that tumor growth fraction assessed by MIB-1 is an important predicator of survival. Cyclin A, like MIB-1, is a recently described specific marker of proliferation, detectable primarily in S phase of the cell cycle as it undergoes progression to G2 phase. Thirty-seven cases of astrocytic tumors--14 cases of World Health Organization grade 1 and 2 (low grade tumors), 8 cases of grade 3 (anaplastic astrocytoma), and 15 cases of grade 4 (glioblastoma multiforme)--were simultaneously evaluated using routine paraffin immunohistochemical methods with commercial antibodies against MIB-1 and cyclin A. The results were quantitated using a Cell Analysis System (CAS) 200 image analyzer. The mean percentage positive nuclear area for MIB-1 was 3.32% in grade 1 and 2, 19.27% in grade 3, and 24.00% in grade 4 astrocytic tumors. Cyclin A showed a similar pattern of positivity in the same cases: 2.84% in grade 1 and 2, 16.27% in grade 3, and 24.88% in grade 4 astrocytic tumors. The data suggest that both proliferation markers correlated significantly with histologic grade. Cyclin A appears to be as good an indicator of brain tumor proliferation as MIB-1. Because cyclin A is detectable primarily in the S phase of the cell cycle, the fraction of cells positive for cyclin A should allow for a more accurate indicator of tumor progression.

Objective: To determine the incidence of human papillomavirus (HPV) DNA by in situ hybridization analysis in women with vulvodynia and suspected HPV infection as compared to normal controls. Methods: A chart review was performed to identify women with vulvodynia and both colposcopic and histologic evidence of HPV infection. Control patients of women with vulvar biopsies for benign, non-HPV related conditions were also identified from the chart review. Vulvar biopsies from 11 women with vulvodynia and 12 control patients were compared by histology and by in situ hybridization for HPV DNA. In situ hybridization was performed with DNA probes for common HPV subtypes: 6,11,16,18,30,31,33,34,45,51, and 52. Positive controls were performed for each HPV subtype. Results: All 11 patients with vulvodynia and both clinical and histologic evidence of HPV infection were negative for all types of HPV DNA by in situ hybridization. The 12 control patients who had no clinical or histologic evidence of active HPV were also negative for HPV DNA by in situ hybridization. Conclusions: DNA from the tested HPV subtypes was not identified in patients with vulvodynia and suspected HPV infection. While it is possible that other HPV subtypes may be involved in vulvodynia, these data suggest that DNA from common HPV subtypes is not identified in greater frequency in patients with vulvodynia as compared to normal controls and suggest that the role of HPV in vulvodynia may be overestimated.

A 52-year-old female presented with a progressively enlarging vulvar mass. Pathological evaluation revealed a high-grade vulvar leiomyosarcoma. Immunohistochemical and ultrastructural studies were performed to support the diagnosis. In an effort to better understand the biology of this tumor additional immunohistochemical studies for the protein product of p53 tumor suppressor gene and estrogen receptor expression by tumor cells, as well as the type of immune cells infiltrating the tumor were performed. Tumor cells showed an overexpression of p53 protein and were estrogen receptor-positive. Macrophages and T and B lymphocytes infiltrated the tumor in moderate numbers with occasional lymphoid aggregate formation. This study is the first attempt to better understand the biology of these tumors.